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J Kingdom

Publications and source records attributed to J Kingdom.

At least 37 records · Page 2Linked to original sources
PubMed1999

Apoptosis cascade progresses during turnover of human trophoblast: analysis of villous cytotrophoblast and syncytial fragments in vitro.

Growth and survival of the trophoblast layer of the human placenta depends on continuous incorporation of villous trophoblast stem cells (cytotrophoblast), by syncytial fusion, into the syncytiotrophoblast. Descriptive studies suggest that this process may be intimately related to apoptosis. We have analyzed the expression and activation of initiator and execution caspases, critical effectors of apoptosis, in relation to trophoblast turnover (differentiation) in human placental villi. We used immunohistochemistry, caspase enzyme histochemistry, caspase activity assays, Western blots, and autoradiography techniques on placental tissue sections, trophoblast lysates, villous explants, and isolated trophoblast fragments (villous cytotrophoblast and mononuclear syncytial elements) in vitro. Our data demonstrate expression of initiator caspases 8 and 10 and activity of caspase 8 in villous cytotrophoblast. Proforms of the execution caspases 3, 6, and 7 were also expressed in villous cytotrophoblast, but activation of execution caspases 3 and 6 could only be demonstrated in the syncytiotrophoblast after syncytial fusion. Down-regulation of the general transcription level (reduced incorporation of [3H]uridine) as well as cleavage of the execution caspase substrates poly-(ADP-ribose)polymerase and lamin B was confined to syncytiotrophoblast and preceded the final events of apoptotic death (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling reactivity and nuclear collapse). Our data confirm that the apoptosis cascade in villous trophoblast is regulated in parallel with trophoblast differentiation, syncytial fusion, and trophoblast turnover.

Apoptosis↗
PubMed1998

Increased fetoplacental angiogenesis during first trimester in anaemic women.

BACKGROUND: Epidemiological studies describe an association between relative size of the placenta at delivery and cardiovascular morbidity and mortality during adult life. Some determinants of placental size, such as maternal anaemia, have been acknowledged, but no plausible mechanism has been advanced to explain the initiation of postnatal disease. METHODS: Placental villous vascularisation in anaemic women (Hb<90 g/L) was assessed in the first and third trimesters of pregnancy by immunohistochemical identification of villous capillaries and compared with that of gestational age-matched groups of women with normal (Hb>110 g/L; control group) concentrations of haemoglobin, and an intermediate group (Hb 90-110 g/L). FINDINGS: Anaemia, especially in the first trimester, was associated with increased numbers of capillaries per villous cross section (mean 11.70 [SE 0.35] vs 4.14 [0.27]) located mainly in the outer third of the stroma beneath the trophoblast (94% [1.15] vs 67% [1.82]) and with increased numbers of villous macrophages and of proliferating MIB-1-positive cells compared with the control group. INTERPRETATION: Maternal anaemia in early pregnancy seems to influence the pattern of placental vascularisation. Such changes might alter placental vascular impedance during early fetal life, thereby exerting important effects on cardiovascular development.

Adult↗
PubMed1998

Prospective non-invasive monitoring of pregnancies complicated by red cell alloimmunization.

Our purpose was to evaluate the impact of non-invasive assessment of fetal anemia and anti-D antibody quantification on the timing and frequency of invasive procedures in pregnancies complicated by rhesus alloimmunization. Nineteen consecutive non-hydropic pregnancies referred to the fetal medicine center were assigned a prior risk category (none/mild, moderate or severe) and monitored by: (1) serial fetal measurements of umbilical vein maximal flow velocity (UVVmax), liver length and spleen perimeter measurements; and (2) serial anti-D antibody concentration. Invasive tests for fetal anemia (amniocentesis or fetal blood sampling) were deferred in the absence of abnormal ultrasound findings and/or rising antibody levels. In six cases serial non-invasive tests were normal with stable antibody levels, and no invasive tests were performed; four infants were mildly affected, one was unaffected and one required postnatal exchange transfusion. In the remaining 13 affected cases, amniocentesis was performed in nine cases for: elevated UVVmax alone (n = 3), elevated UVVmax and an increased antibody level (n = 2), or normal UVVmax with an increased antibody level (> 15 IU/ml) and severe prior risk category (n = 4). Six fetuses underwent fetal blood sampling (initial hematocrit 9-29%), and five of these had an elevated UVVmax. Liver length and spleen perimeter measurements were increased in only one anemic fetus (hematocrit 13%). Of 17 infants born alive, an elevated UVVmax prior to delivery was predictive of the need for exchange transfusion (six of seven cases with an elevated UVVmax vs. one of ten with a normal UVVmax; chi 2 = 5.73, p = 0.017 with Yates' correction). These preliminary data suggest that pregnancies with a mild or no history of fetal anemia may be monitored by a combination of serial antibody quantification and Doppler monitoring of UVVmax.

Adult↗
PubMed1998

Objective and subjective assessment of abnormal uterine artery Doppler flow velocity waveforms.

OBJECTIVE: Abnormal uterine artery Doppler waveforms in the second trimester of pregnancy can predict adverse outcome. The presence of a diastolic notch is a better predictor than measurement of impedance indices. A notch has generally been assessed subjectively, which has raised questions as to the reproducibility of the method. The aim of this study was to compare subjective and objective assessments of 50 abnormal waveforms. DESIGN: This was a retrospective study of 50 abnormal uterine artery waveforms collected during a previous screening study. Subjective and objective assessments were compared and related to adverse outcomes. Five impedance indices incorporating a measurement of the diastolic notch were compared. Three indices predictive of adverse outcome were compared to subjective assessment. RESULTS: There was good agreement between experienced operators in their subjective assessment of uterine artery waveforms. Adverse outcome was predicted by only moderately or severely abnormal waveforms. Three impedance indices predictive of adverse outcome were the pulsatility index (PI), A/C and (D - C)/B (where A is the peak systolic, D is the maximum diastolic and B is the end-diastolic frequency, and C is the nadir of the notch). The cut-off values combining the highest sensitivity for the lowest false-positive rate were 1.5 for PI, 3.0 for A/C and 0.15 for (D - C)/B. A PI of 1.5 had the highest sensitivity (100%) and positive predictive value (55%) for adverse outcome in this preselected group. These three indices were compared to subjective assessment using the kappa index and the (D - C)/B ratio had the closest agreement, although all three indices showed at least moderate agreement. The cut-off values of 1.5, 3.0 and 0.15 for PI, A/C and (D - C)/B, respectively appear to differentiate between mildly abnormal waveforms and moderately/severely abnormal waveforms. CONCLUSION: Objective assessment of uterine artery waveforms using cut-off values of PI, A/C and (D - C)/B provides an estimation similar to that provided by subjective assessment by an experienced operator. These ratios will now need to be used prospectively in an unselected population to compare their screening properties.

Arteries↗
PubMed1997

Opioids in labor.

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Analgesia, Epidural↗
PubMed1997

Characterization of P2 receptors for purine and pyrimidine nucleotides in human placental cotyledons.

1. The aim of this study was to characterize P2 receptors in the arterial vascular bed of human perfused placental cotyledons. Vasoconstrictor responses to bolus injections of purine and pyrimidine nucleotides were tested at basal tone, and vasodilator responses in preparations with tone raised by perfusion with prostaglandin F2alpha (PGF2alpha; 10-50 nM). 2. At basal tone, bolus injections of the P2X-selective agonist alpha,beta-methylene ATP (alpha,beta-meATP; 0.5-500 nmol) elicited dose-dependent vasoconstriction. ATP (0.005-5 micromol) also elicited dose-dependent vasoconstriction, but was less potent than alpha,beta-meATP. Vasoconstriction was also elicited by other nucleotides, but only at the highest dose tested (5 micromol): UTP > CTP = ITP (n = 6). GTP and TTP did not cause vasoconstriction. 3. Constrictor responses to bolus injections of alpha,beta-meATP were resistant to desensitization and were not significantly affected when carried out in the presence of 1 microM alpha,beta-meATP added to the perfusate. However, responses to bolus injections of alpha,beta-meATP were partially blocked by perfusion with 10 microM alpha,beta-meATP. In contrast, responses to ATP and UTP were unaffected by 10 microM alpha,beta-meATP. The P2X receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 10 and 100 microM) had no significant effect on vasoconstriction mediated by alpha,beta-meATP and ATP. 4. Removal of the endothelium had no significant effect on constrictor responses to alpha,beta-meATP, ATP and UTP. Inhibition of nitric oxide (NO) synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME; 100 microM) had no significant effect on vasoconstriction to ATP and alpha,beta-meATP. 5. In preparations with tone raised with PGF2alpha (10-50 nM) vasodilatation was elicited by nucleotides with the following order of potency: 2MeSATP = ADP >> ATP > UTP > CTP = GTP = ITP = TTP. pD2 values were: 2MeSATP, 10.03+/-0.26 (n=7); ADP, 9.97+/-0.40 (n=5); ATP, 8.89+/-0.18 (n=7); UTP, 7.79+/-0.35 (n=7). Maximal responses to 2MeSATP and ADP were similar and were approximately 40% greater than maximal responses to ATP and UTP. 6. Vasodilator responses to nucleotides were abolished by L-NAME (100 microM) and by removal of the endothelium. 7. In conclusion, contractile responses mediated by alpha,beta-meATP and ATP in human placental smooth muscle are resistant to desensitization and insensitive to PPADS and, thus, show a dissimilar pharmacological profile to the classic smooth muscle P2X1 receptor. There may be two subtypes of smooth muscle P2 receptor based on differential antagonism of alpha,beta-meATP and ATP with alpha,beta-meATP. A smooth muscle P2 receptor mediates vasoconstriction to UTP, and may indicate a further subtype. Endothelium-dependent, NO-dependent, vasodilatation to 2MeSATP and ADP may be mediated by P2Y1 receptors, while endothelial P2Y2 receptors are likely to mediate NO-dependent relaxation to ATP and UTP.

Adenosine Triphosphate↗
PubMed1997

The case for routine determination of chorionicity and zygosity in multiple pregnancy.

Twin pregnancy has a disproportionate effect on perinatal mortality, being six times higher than for singleton gestations. The major threats to perinatal survival are from two very different pathological processes: spontaneous preterm delivery, and the interlacing clinical complications of monochorionicity. With the realization that perinatal loss/handicap is higher in monochorionic than dichorionic twins, attempts have been made in the last decade to assign chorionicity ultrasonographically, using single or composite parameters, such as number of placental masses, fetal sex, septal thickness and twin peak signs. Such knowledge will allow (a) risk stratification of twin gestations, (b) appropriate selection of prenatal screening and diagnostic methods, (c) vigilant monitoring for early diagnosis of twin-twin transfusion syndrome and growth restriction, and (d) management of preterm labour, congenital malformation, single intra-uterine death and polyhydramnios. By contrast, prospective knowledge of zygosity is unlikely to influence perinatal outcome, since approximately 25 per cent of monozygous conceptions have dichorionic placentation. Postnatal determination of zygosity in like sex twin pairs with dichorionic placenta is important for the future consideration of organ transplantation compatibility and to evaluate the genetic component of various diseases.

Chorion↗
PubMed1995

Methods for the transcervical collection of fetal cells during the first trimester of pregnancy.

Before termination of pregnancy, four techniques for retrieving fetal cells transcervically were investigated: uterine lavage, endocervical lavage, cytobrush and mucus aspiration. The yield of fetal cells in these samples was studied and found to be somewhat better after uterine lavage. A preliminary assessment of the safety of mucus aspiration was carried out before transcervical chorionic villus sampling (CVS) in continuing pregnancies. No difference in outcome to a control group having only CVS was found.

Biopsy↗
PubMed1995

Detection of trophoblast cells in transcervical samples collected by lavage or cytobrush.

OBJECTIVE: To compare two methods of obtaining fetal cells from the endocervical canal for prenatal diagnosis during the first trimester: lavage with physiologic saline, and the endocervical passage of a cytobrush. METHODS: Fetal cells were identified morphologically using conventional and immunohistochemical staining. Y-specific sequences were detected using polymerase chain reaction (PCR) and fluorescent in situ hybridization. The presence of fetal DNA was also demonstrated by PCR amplification of a polymorphic short tandem repeat marker. RESULTS: Syncytiotrophoblast cells were identified in four of 11 lavage samples and in one of 11 brush samples. Sex determination using fluorescent in situ hybridization was achieved in all 11 lavage samples and in nine of 11 cytobrush samples; no Y sequences were located in two brush samples from male embryos. Sex determination was achieved successfully in all 22 samples using PCR of X- and Y-specific DNA sequences. Small tandem repeat pattern analysis indicated the presence of fetal DNA in five of 11 lavage samples and in one of eight cytobrush samples, which were informative because the maternal and fetal small tandem repeat patterns differed. CONCLUSION: Although lavage retrieves more trophoblast cells than does brushing, both methods are potentially suitable for molecular prenatal diagnosis.

Female↗
PubMed1995

[Unexplained increase in maternal plasma in alpha-fetoproteins in the second trimester of pregnancy: perinatal results].

To determine the relation between adverse perinatal events and an unexplained mid-trimester elevation in maternal serum alpha-fetoprotein (MSAFP) in an unselected population, 16,093 women with a singleton pregnancy delivered between January 1985 and November 1991, at the Queen Mother's Hospital, Glasgow, Scotland, were studied. The elevated MSAFP group (n = 606) was associated with an increased risk of preterm delivery (odds ratios/95% confidence intervals) (3.7/2.6-5.2), small or gestational age (4.5/3.3-6.1), intrauterine death (3.9/1.7-9.4), and placental abruption (3.2/1.5-6.7). The risks increased with MSAP concentration. An unexplained mid-trimester elevation of MSAFP is associated with increased risk of adverse perinatal events, thus acting as a non-specific marker o a "high risk pregnancy". Alterations to current antenatal management in this group may improve prognosis.

Female↗
PubMed1994

Midtrimester chorionic villus sampling: an alternative approach?

OBJECTIVE: Our purpose was to audit midtrimester chorionic villus sampling after a positive maternal serum screening test for autosomal trisomy. STUDY DESIGN: From January 1990 until July 1993 chorionic villus sampling was offered to all screened positive women. RESULTS: Five hundred fifty-one mothers had chorionic villus sampling. The mean age was 31.7 years. The mean gestational age was 18.2 weeks. The mean time for direct karyotyping was 4.4 days and for culture results 20.2 days. Results were obtained in 99.6% of samples: direct plus culture results in 94%, direct results alone in 2.3%, and culture results alone in 3.3%. Fourteen pregnancies had abnormal karyotypes. There were five cases of placental mosaicism and one false-positive result. The loss rate was 0.4%. CONCLUSION: Midtrimester chorionic villus sampling, which is easier to perform than cordocentesis, provides a rapid and reliable karyotype. The complication rate is comparable to that of other invasive procedures.

Adult↗
PubMed1992

Spontaneous cessation of umbilical blood flow in the acardiac fetus of a twin pregnancy.

The acardiac fetus is a rare entity found only in monozygotic multiple pregnancy. Although the acardiac fetus is non-viable, the perinatal mortality rate for the normal fetus may be as high as 50 per cent, and is usually associated with fetal heart failure and hydrops fetalis, or as the result of prematurity. In this communication, we describe a case of spontaneous cessation of blood flow to an acardiac fetus and discuss the management of this condition with special reference to optimizing the outcome for the normal fetus.

Abnormalities, Severe Teratoid↗
PubMed1990

Interaction of angiotensin II and atrial natriuretic peptide in the human fetoplacental unit.

We have identified two classes of membrane receptor for atrial natriuretic peptide (KD (dissociation constant) 0.2, 70.1 nmol/L) and angiotensin II (KD 1.7 nmol/L, 15.2 nmol/L) in human fetoplacental vasculature. In addition, in the isolated perfused placenta atrial natriuretic peptide inhibited the vasoconstrictor action of angiotensin II. These findings suggest that atrial natriuretic factor may regulate fetoplacental blood flow.

Angiotensin II↗