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G J Burton

Publications and source records attributed to G J Burton.

At least 19 recordsLinked to original sources
PubMed1997

Morphological analysis of degeneration and regeneration of syncytiotrophoblast in first trimester placental villi during organ culture.

We have recently shown using dansyl-L-lysine exclusion studies that the release of human chorionic gonadotrophin (HCG) in conjunction with L-lactate dehydrogenase (LDH) from first trimester villi during organ culture is symptomatic of syncytiotrophoblast degeneration. The purpose of this study was to examine chorionic villi at the ultrastructural level in order to determine events occurring during organ culture. The tissue was sampled after 0, 24, 48 and 120 h in culture and processed for electron microscopy. In addition to confirming the previously recorded syncytial degeneration, the electron micrographs showed clearly the generation of a new syncytiotrophoblast layer. The new layer, derived from differentiating cytotrophoblast cells, was largely formed by 48 h and was maintained for at least 120 h in culture. This study demonstrates a model which provides an opportunity to study the differentiation of cytotrophoblast cells whilst they retain their anatomical relationships within the villous structure.

Chorionic Villi↗
PubMed1996

Significance of placental damage in vertical transmission of human immunodeficiency virus.

The significance of physical breaches of the trophoblastic layer of the placenta in transmission of HIV from mother to infant was evaluated in 17 HIV-infected pregnant women. Samples of peripheral blood were obtained from the women during pregnancy and at delivery, at which time a small piece of placental tissue was obtained from a random site and immediately placed into fixative. Blood samples were obtained from infants at or shortly after birth and thereafter at approximately 3-month intervals, until the age of 18 months, in order to determine their HIV infection status. HIV RNA and p24 antigen were quantified in maternal plasma and CD4 cells enumerated. Paediatric diagnosis was conducted using polymerase chain reaction, virus isolation, detection of p24 antigen, and measurement of class-specific antibodies. Placental damage was quantified and evaluated using transmission electron microscopy. Maternal viral load was low, with a mean RNA copy number of 8,237 per millilitre of plasma (range 230-37,233 copies/ml). Only two women were p24-antigenaemic, and CD4 numbers ranged from 0.09 to 2.8 x 10(9)/l. There was evidence of breaks in the trophoblastic surface to the depth of the basement membrane in all 17 placentas, and perivillous fibrinoid deposits were also observed to a varying degree in all samples. However, none of the 13 infants available for follow-up had evidence of infection with HIV. Superficial damage to the trophoblastic surface of the placenta, with exposure of the basement membrane and potential exposure of CD4-expressing cells, does not appear to be a significant factor in the transmission of HIV from mother to infant during pregnancy.

Female↗
PubMed1996

An in vitro model for the study of wound healing in first trimester human placenta.

The placenta operates as a vital interface between the mother and fetus. In addition to facilitating fetal nourishment, it acts as a barrier both to potentially deleterious agents and to contact between their two immune systems. As a consequence, damage to the placenta, even on a relatively small scale, could be very dangerous to the fetus. Therefore, wound repair mechanisms are likely to be of great importance in ensuring that an intact placental barrier is re-established as soon as possible. By use of an in vitro method for injuring and subsequently culturing small pieces of first trimester villous tissue, we have observed a number of indications that a wound response is initiated. Pronounced expression of transforming growth factor-beta1, heavy infiltration of macrophages and late deposition of tenascin in the region of the wound all provide good evidence of some form of healing activity. Furthermore, we have noted that these indicators are suggestive of 'adult-type' rather than 'fetal-type' repair processes.

Female↗
PubMed1996

Increased incidence of placental chorioangioma in high-altitude pregnancies: hypobaric hypoxia as a possible etiologic factor.

OBJECTIVES: Our purpose was to determine the effects of pregnancy at high altitude on the human placental structure. STUDY DESIGN: Histologic material from 22 term placentas delivered at altitudes above 3600 m was examined and compared with control material from 760 m. RESULTS: Intraplacental chorioangiomas were identified in 5 of the 22 high-altitude placentas but in none of the 59 controls. The lesions were not visible on the external surface of the placentas and were not encapsulated. The state of differentiation varied; some contained numerous capillaries that showed sinusoidal dilations, whereas in others at the opposite extreme mesenchymal cells predominated. The presence of chorioangiomas was frequently associated with threatened premature delivery, a circumvallate placenta, and multiple infarction. The lesions represented only a small percentage of the overall placental volume (<10%). CONCLUSIONS: The increased incidence of placental chorioangioma observed at high altitude (above 3600 m) may be due to the prevailing hypobaric hypoxia. Overexpression of angiogenic cytokines such as vascular endothelial growth factor, which is known to be up-regulated by this factor in vitro, may mediate this effect.

Adult↗
PubMed1996

Stereological evaluation of vascular adaptations in human placental villi to differing forms of hypoxic stress.

The aim was to determine whether the fetal vasculature of the human placenta adapts in a uniform manner to different forms of hypoxic stress. Stereological analyses were performed on the intermediate and terminal villi of placentae obtained from each of the following conditions; high altitude (up to 2800 m), maternal iron-deficiency anaemia and pre-eclampsia. These conditions were taken to represent hypoxic, anaemic and ischaemic hypoxia, respectively. In each situation, there was a trend for the volume fraction of the fetal capillaries to be higher than in the controls, although the differences were statistically significant only for the cases of hypoxic and anaemia hypoxia. This was due, in part, to capillaries being of larger diameter. Evidence for capillary proliferation was inconsistent. At high altitude there was a trend for the capillary length density to be raised, but there was no change in the ratio of capillary:villous length. In both maternal anaemia and pre-eclampsia the capillary length density remained constant, but the ratio of capillary:villous length was significantly raised in the former. These results suggest that dilatation of the capillary sinusoids, with accompanying thinning of the villous membrane, is the principal adaptation to hypoxia under the conditions studied.

Altitude↗
PubMed1996

Does hypercapillarization influence the branching pattern of terminal villi in the human placenta at high altitude?

This study tests the hypothesis that exposure of the placenta to hypobaric hypoxia at altitude results in an altered branching pattern of the villous tree. Histological material from 20 term placentae delivered at altitudes over 3000 m was compared with matched controls from 500 m. Estimates of the mean star volume of intermediate and terminal villous domains were 1.40 x 10(6) microns3 (s.d. 0.63) in the high altitude group and 1.90 x 10(6) microns3 (s.d. 0.34) in the controls (F = 9.07, P < 0.005). The volume fraction of the villous tree occupied by trophoblastic bridges and syncytial knots was 8.1 per cent (s.d. 3.5) in the high altitude group and 3.2 per cent (s.d. 1.6) in the controls (F = 29.45, P < 0.0001). Previous studies have shown that the majority (80 per cent) of bridges are artefacts caused by the plane of section passing tangentially through the trophoblast layer at points of villous bending or branching. The results are, therefore, consistent with the hypothesis that peripheral villi are shorter, knob-like protrusions at high altitude, clustered more closely together. This modified branching pattern was confirmed by scanning electron microscopy. The change in architecture may be due to enhanced angiogenesis stimulated by the lower partial pressure of oxygen prevailing at high altitude.

Adult↗
PubMed1995

Placental histomorphometry and morphometric diffusing capacity of the villous membrane in pregnancies complicated by maternal iron-deficiency anemia.

OBJECTIVE: Our purpose was to determine the morphometric diffusing capacity of the human placental villous membrane in cases of maternal iron-deficiency anemia. STUDY DESIGN: Material from 10 term placentas from mothers with hemoglobin levels < 10 gm/100 cm3 was compared stereologically with control material from women with normal hemoglobin concentrations matched for age and parity. Data were compared with Student t test. RESULTS: Birth and placental weights were constant between the two groups. Maternal anemia was associated with a significant reduction in both volume and surface area of intermediate and terminal villi (157.8 vs 234.5 cm3 and 9.5 vs 14.9 m2, respectively). There was a concomitant rise in the volume of pathologic areas (32.1 vs 4.1 cm3). Harmonic mean thickness of the villous membrane was significantly less in the anemia cases (5.86 vs 7.15 microns), because of an increase in volume fraction of the fetal capillaries. Consequently, the morphometric diffusing capacity of the villous membrane was maintained (4.49 vs 5.31 cm3.min-1.mm Hg-1, t = 1.04, p > 0.05). CONCLUSIONS: There is a reduction rather than an enlargement of the placental villous tree in cases of maternal anemia. This may be because of underlying malnutrition. Nonetheless, the placenta adapts through thinning of the villous membrane so that diffusing capacity is maintained at normal levels.

Anemia, Iron-Deficiency↗
PubMed1995

Human term placental capillary endothelial cell specialization: a morphometric study.

In the human placental capillary endothelium, two cell types have previously been described with different organelle distribution patterns. This observation was based on examination of cross-sectional profiles. It is known, however, that organelle distribution may vary in different parts of a cell. The present study was undertaken to estimate morphometrically the pattern of organelle distribution in normal term placental capillary endothelium. Ten normal term placentae were processed routinely for electron microscopy. The volume fractions of the different organelles were determined in both the perinuclear and peripheral parts of the cells. In addition, comparisons were made between endothelial cells at the site of vasculosyncytial membranes (VSM) and those forming the remainder of the capillary wall (non-VSM). Multifactor ANOVA showed there was a significant difference between the perinuclear and the peripheral parts in the volume fractions of mitochondria, rough endoplasmic reticulum, intermediate filaments, all these being more in the perinuclear region, whilst vesicles and cytosol were more prevalent in the peripheral parts. In contrast, there was no significant difference between the regions of VSM and the non-VSM except for the volume fractions of microfilaments which were higher in the non-VSM region.

Capillaries↗
PubMed1995

The distribution of microvilli over the villous surface of the normal human term placenta is homogenous.

The study was carried out to estimate stereologically whether regional differences exist in the distribution of microvilli between vasculo-syncytial (VSM) and non-vasculo-syncytial (non-VSM) areas of the villous surface in normal term placenta. In ten placentae a normal lobe was perfusion-fixed at a pressure of 60 mm Hg, and the intervillous space was perfused at 10 mm Hg. The tissue was routinely processed for ultrastructural examination. Stereological estimates relating to the length and diameter of microvilli, and to the villous surface amplification factor in adjacent but contrasting (VSM and non-VSM) regions, were obtained. A paired "t' test showed no significant difference in the villous surface amplification factor between the two regions (5.18 +/- 0.54 and 5.22 +/- 0.54 respectively, mean +/- s.e.m. P > 0.05). In addition, there were no significant differences between the length and diameter of microvilli in both regions (P > 0.05 in both). The results confirm that the normal term placenta has a continuous and even covering of microvilli over the syncytium.

Female↗
PubMed1995

Sonographic, stereological and Doppler flow velocimetric assessments of placental maturity.

OBJECTIVE: To determine whether sonographic assessments of increasing placental maturity are associated with changes in the theoretical diffusing capacity of the organ and with changes in vascular resistance. DESIGN: Placental maturity was assessed sonographically in 10 organs: five were classified as completely immature and five as completely mature. Doppler flow velocimetric recordings were obtained shortly before delivery performed by elective caesarean section. Placental biopsies taken immediately after delivery were analysed stereologically. RESULTS: No differences were observed in either placental weight or volume, but the morphometric diffusing capacity of the villous membrane was 40% higher in the mature than in the immature placentas. Doppler indices did not alter with increasing placental maturity. CONCLUSIONS: Normal term placentas differ significantly in their diffusion characteristics, even when organ weight and volume remain constant. Umbilical vascular resistance may be heavily influenced by the number of parallel circulatory units offered by the placental lobules.

Blood Flow Velocity↗
PubMed1994

Effects of hypobaric hypoxia on the fetoplacental unit: the morphometric diffusing capacity of the villous membrane at high altitude.

OBJECTIVE: Our purpose was to determine whether the human placenta is able to adapt structurally to hypobaric hypoxia so as to increase its diffusing capacity. STUDY DESIGN: Material from 10 normal term placentas collected at each of three altitudinal levels in Kirghizstan was analyzed stereologically. Data were compared by one-way analysis of variance. RESULTS: Within the overall sample group birth weight and placental weight remained constant. There were no differences in villous and capillary surface areas or capillary length, but capillary volume increased from 37.9 cm3 in controls (700 m) to 50.8 cm3 at high altitude (2200 to 2800 m). The harmonic mean thickness fell from 6.9 microns in controls to 4.8 microns at high altitude. Consequently, the morphometric diffusing capacity of the villous membrane for oxygen increased from 4.22 to 7.56 cm3.min-1.mm Hg-1 (F = 6.45, p < 0.05). CONCLUSIONS: The placenta is capable of adapting to hypobaric hypoxia to increase its functional capacity for gaseous exchange. This is principally through a reduction in the thickness of the villous membrane.

Altitude↗
PubMed1994

The effects of maternal vascular pressure on the dimensions of the placental capillaries.

OBJECTIVE: The study sought stereological evidence for the sluice flow phenomenon in the human term placenta. DESIGN: Two series of experiments were conducted on caesarean delivered placentae. In both, two fetal arteries were cannulated and perfused. In the first series, five placentae were perfusion-fixed under arterial pressures of 40 mmHg and 60 mmHg, and an external pressure of 10 mmHg in the intervillous space. In the second series, five placentae were perfusion-fixed at arterial pressures of 70 mmHg and 90 mmHg with an external pressure of 30 mmHg. Stereological estimates relating to the size of the capillaries and the thickness of the villous membrane were then made. RESULTS: In each series, as the arterial pressure rose, there was an increase in the volume fraction and surface area of the fetal capillaries, and a concomitant decrease in the mean thickness of the villous membrane. These changes were negated as the external pressure rose, indicating the importance of the pressure differential between the capillary lumen and the intervillous space in determining the dimensions of the fetal capillaries. CONCLUSIONS: The study demonstrated that placental capillaries are elastic and hence deformable. If a sufficiently high pressure is generated in the intervillous space, they may therefore be compressed. This may explain the increase in umbilical vascular resistance demonstrated by doppler studies in pregnant women scanned in the supine position. In this situation the venous drainage from the intervillous space is believed to be impeded by the gravid uterus compressing the inferior vena cava.

Arteries↗
PubMed1994

Significance of changes in fetal perfusion pressure to factors controlling angiogenesis in the human term placenta.

The objective of the study was to determine the effects of mechanical factors on endothelial proliferation in the human placental villous vasculature. Individual fetal lobules were perfused with tissue culture medium at two different standard pressures (40 and 100 mm Hg). The perfused area was then removed and diced into small blocks which were quench frozen in liquid nitrogen. Cryostat sections were obtained and fixed in acetone at 4 degrees C. Proliferating cell nuclear antigen was then identified using Ki67 antibody as a marker. Proliferating nuclei were scored, using a light microscope, and a comparison made between the two pressures used. More proliferating endothelial nuclei were found at 100 mm Hg than at 40 mm Hg (P < 0.05). It is therefore concluded that mechanical factors may play a role in villous angiogenesis and the formation of terminal villi.

Blood Vessels↗
PubMed1993

A scanning electron microscopic study of the chick chorioallantoic membrane: cell death and the involvement of oxygen free radicals.

Cell death is a normal feature within the chick chorioallantoic membrane, occurring principally between days 10 and 14 of incubation. Samples of chorioallantoic membrane were obtained on days 6, 8, 10, 12 and 14 of incubation, after the creation of artificial air chambers on day 3. These were examined by scanning electron microscopy (SEM), transmission electron microscopy (TEM) after staining for acid phosphatase activity, and by light microscopy after demonstrating oxygen free radicals with nitro blue tetrazolium. On day 6, small defects in the plasmalemma, approximately 200 nm in diameter, could be seen by SEM. A sequence of events leading to complete destruction of the plasmalemma, with exposure of the nucleus and other cytoplasmic organelles, could be traced, and by day 8 the membrane was a mosaic of healthy cells and others in various stages of degeneration. TEM revealed that acid phosphatase activity was confined to the golgi apparatus and associated vesicles even in advanced stages of degeneration. By comparison, oxygen free radicals were demonstrated in individual cells from day 6 onwards. Application of superoxide dismutase and catalase to the epithelium using a nebuliser spray significantly reduced the amount of cell death seen by scanning microscopy on day 12. It is concluded that oxygen free radicals may mediate cell death in the chorioallantoic membrane.

Acid Phosphatase↗
PubMed1993

Star volume estimates of the intervillous clefts in the human placenta: how changes in umbilical arterial pressure might influence the maternal placental circulation.

The study estimated the mean volume of the clefts between adjacent villi in the normal term human placenta, and the effect on this of increasing the fetal perfusion pressure, using a new stereological tool called the 'star volume estimator'. This enables the measurement of irregular and complex structures, including both particles and cavities, in a mathematically defined and unbiased manner. To achieve this, a total of ten term placentae delivered by caesarean section were obtained. Four fetal arteries supplying opposite quadrants of the placental disc were perfusion-fixed under standard pressures of 40, 60, 80 and 100 mmHg respectively. Stereological estimates relating to the star volume of the clefts between the villi, and to the volume density of the intervillous space were obtained. There was a significant rise in the star volume of the intervillous clefts from 26.8 x 10(4) m3 at 40 mm Hg to 75.1 x 10(4) m3 at 100 mmHg (F = 75, df = 1.38, P < 0.05). The volume density of the intervillous space remained unchanged, thus obviating the possibility of fluid leakage into the intervillous space accounting for this change. It is concluded that the fetal vasculature provides hydraulic support to the villous tree, and that changes in the umbilical perfusion pressure can therefore alter the disposition of the villi within the intervillous space. As fetal blood pressure rises, for example during acute hypoxic episodes, the villi will move apart. The enlargement of the clefts between adjacent villi will have a secondary effect upon the maternal circulation, promoting more even perfusion of the intervillous space at higher overall flow rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1992

Development of the chick chorioallantoic capillary plexus under normoxic and normobaric hypoxic and hyperoxic conditions: a morphometric study.

Fertile eggs from the domestic fowl were incubated under normobaric normoxic (21% O2), hypoxic (14% O2), and hyperoxic (40% O2) conditions in order to examine the influence of the prevailing oxygen level on the growth and maturation of the chorioallantoic membrane. Eggs were sampled at regular stages throughout incubation for morphometric analysis. Under normoxic conditions, maturation of the capillary plexus occurred in two distinct stages, both of which contributed to a reduction in the thickness of the air-blood barrier. Between days 6 and 10, the capillaries sprouted and fused to form a dense plexus. Subsequently, between days 10 and 14, this plexus invaginated into the chorionic epithelium. Differentiation of the chorioallantoic membrane appeared maximal by the end of this period. Hypoxia resulted in diminished growth of the embryo and chorioallantoic membrane, but in accelerated maturation of the capillary plexus. Hyperoxia had a less marked effect but appeared to retard the final invagination of the plexus, resulting in a thicker air-blood barrier.

Allantois↗
PubMed1992

Formation of vasculo-syncytial membranes in the human placenta.

Vasculo-syncytial membranes are localised areas of the placental villous membrane where the thickness of the barrier separating the maternal and fetal circulations is reduced to as little as 1-2 microns. Consequently, they are believed to be important sites for diffusional exchange. The morphological appearances suggest that they are caused by the obtrusion of locally dilated segments of the fetal capillaries into the trophoblast layer. This study sought quantitative evidence for the hypothesis by performing stereological analyses on vasculo-syncytial membranes at the electron microscopic level. The results confirmed that a strong relationship existed between the thickness of the capillary endothelium and that of the overlying stromal and trophoblastic tissue at these sites (r = 0.47, P < 0.001), indicating that some asymmetrical stretching or remodelling of the capillary wall was involved. Comparisons were also made between the thickness of the trophoblastic, stromal and endothelial components of the villous membrane in villi obtained from the central and from the peripheral parts of placental lobules, where vasculo-syncytial membrane formation is accentuated. The mean thickness of each component was lowest in the samples from the peripheral region, although the differences only proved to be statistically significant for the stromal layer (P = 0.01). Both sets of data lend quantitative support to the hypothesis that vasculo-syncytial membrane formation is the result of obtrusion of locally dilated segments of the fetal capillaries. The way in which this may be linked to changes in the dynamics of the fetal circulation as gestation advances is discussed.

Capillaries↗