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K R Page

Publications and source records attributed to K R Page.

33 records · Page 2Linked to original sources
PubMed1987

Critical role of iodination for T cell recognition of thyroglobulin in experimental murine thyroid autoimmunity.

We have used two clonotypically distinct thyroglobulin (Tg)-specific, I-Ak restricted monoclonal T cell populations to investigate the role of thyroid peroxidase-catalyzed iodination in Tg recognition by autoreactive T cells. The results showed that these T cells could recognize Tg only it it was sufficiently iodinated. Unlike normal mouse Tg, noniodinated mouse Tg was unable to induce significant thyroid lesions but could trigger the production of Tg autoantibodies. In these experiments, the importance of T cell recognition of iodination-related epitopes was emphasized by the inability of serum antibodies to distinguish Tg on the basis of iodine content, whether they were induced with normal or noniodinated Tg. Therefore, thyroid peroxidase-dependent modification of Tg would appear to be central to its recognition by autoreactive T cells and hence its capacity to induce autoimmune thyroid lesions.

Amitrole↗
PubMed1987

Calcium transport across the isolated dually perfused human placental lobule.

1. Movements of 45Ca and 3H2O in maternal to fetal (M----F) and fetal to maternal (F----M) directions across the dually perfused isolated human placental lobule were measured under steady-state conditions. 2. M----F values of the clearances (CR) and extractions (ER) of 45Ca relative to 3H2O were 0.371 +/- 0.056 and 0.492 +/- 0.086 (mean +/- S.E. of mean) respectively. The corresponding values for F----M movements were 0.277 +/- 0.017 and 0.251 +/- 0.010 respectively. The F----M perfusion flow ratio (QF/QM) was 0.34 +/- 0.01 throughout. Comparison with previously published data indicated a significant degree of membrane limitation to Ca transfers. 3. There was evidence of a mismatch between tissues receiving a fetal and those receiving a maternal perfusion. 4. The relative extraction ER was markedly and reversibly enhanced when perfusate total Ca was reduced from 2.4 to 0.1 mM. The effect was present in both M----F and F----M transfers and provided evidence for carrier-mediated uptake of Ca on both aspects of the placental barrier. Small and transient decreases in the relative clearance CR were observed on changing from 2.4 to 0.1 mM-Ca in M----F and to a lesser extent F----M transfers while transient increases were seen on changing from 0.1 back to 2.4 mM-Ca. 5. Measurement of net changes in Ca levels in closed-circuit studies indicated a significant release of both ionized (Ca2+) and total (CaT) Ca into the fetal perfusate at total Ringer solution concentrations of 1.4, 1.9 and 2.4 mM-Ca. Release of Ca into the maternal circuit was also observed using 1.4 mM-Ca Ringer solution but when 1.9 and 2.4 mM-Ca Ringer solution was used a net uptake occurred. 6. These findings strongly suggest that mechanisms by which Ca is transferred from M----F circulations in vivo are at least partly preserved in the in vitro human placental preparation. They indicate that this preparation is suitable for the study of these mechanisms and their regulation by hormonal and other factors.

Biological Transport↗
PubMed1986

Evidence of saturable uptake mechanisms at maternal and fetal sides of the perfused human placenta by rapid paired-tracer dilution: studies with calcium and choline.

Rapid uptake and efflux of 45Ca2+ and [3H]choline at the maternal and fetal interfaces of the syncytiotrophoblast in the dually-perfused human placenta was investigated by application of the single circulation paired-tracer dilution method (Yudilevich, Eaton, Short & Leichtweiss 1979). Cotyledons were perfused with Krebs-bicarbonate containing dextran (30 g/l; MW = 60-70,000) at 20 and 6 ml/min on maternal and fetal sides, respectively. The paired-tracer (test substrate and extracellular marker) technique consisted of an intra-arterial injection of a tracer bolus, followed by venous sampling over 5-6 min. There was a rapid (sec) uptake of 45Ca2+, followed by backflux (efflux into the ipsilateral circulation) which, over 5-6 min, was 59-100% on the fetal side. It was more variable but generally lower on the maternal interface. At 0.1 mM calcium, 45Ca2+ maximal uptake (Umax) was about 53% on the fetal side but on the maternal side it was variable and averaged 17%. At 2.4 mM calcium fetal side Umax was reduced to 40%. However, on the maternal side the effect was not consistent. Unidirectional influx (nmol/min per g) appeared to be not different on the two sides of the placenta. For [3H]choline (in choline-free perfusates) Umax was about 50% and 30% on fetal and maternal sides, respectively; tracer backflux was variable on the maternal side and averaged 50% on the fetal side. [3H]Choline uptake was highly inhibited by either 1.0 mM choline or the specific competitive inhibitor, hemicholinium-3 (0.1 mM). Specific transplacental transfer of 45Ca2+ (i.e. in excess of the extracellular marker) was not significant in either direction. For [3H]choline there was an apparent small excess (about 4%) preferential towards the fetal circulation. These findings in the human placenta are similar to those demonstrated previously in the guinea-pig placenta which suggested the existence of specific transport systems for choline and calcium on both sides of the syncytiotrophoblast.

Biological Transport, Active↗
PubMed1984

The effect of prostaglandin D2 on the blood vessels of the perfused isolated cotyledon of the human placenta.

Prostaglandin D2 was shown to constrict the blood vessels of the isolated perfused cotyledon of the human placenta. Its potency was less than that of prostaglandin F2 alpha but similar to prostaglandin E2. As it is known to dilate uterine blood vessels it may, by its differential action on the foetal and maternal vascular beds, play a role in the local regulation of utero-placental blood flow.

Dinoprost↗
PubMed1983

Effect of angiotensin II and 5-hydroxytryptamine on the vessels of the human foetal cotyledon.

1 The actions of angiotensin II (AT II) and 5-hydroxytryptamine (5-HT) on the vessels of the human isolated, perfused, cotyledon were examined in vitro. 1 The cotyledonary vessels were shown to respond to both AT II and 5-HT over the range 10(-8) to (10(-4) M. 3 The preparation was found to be more responsive to AT II than 5-HT. 4 The findings confirm that the responsiveness of the cotyledonary vessels differs from the vessels of the umbilical cord, and that this behaviour does not depend upon the integrity of the endothelium associated with these vessels.

Angiotensin II↗
PubMed1981

A Teorell oscillator system with fine pore membranes.

A Teorell membrane oscillator system has been investigated theoretically and experimentally. Instead of the broad pore (e.g., glass sinter) membranes used by Teorell and other investigators, we used membranes of a hydrodynamic permeability lower by factor of 10(3)-10(5) and a fixed ion concentration higher by a factor of 10(2)-10(5). A system with such membranes was thought to be a more adequate analogue of excitable biological tissues (for which the Teorell oscillator had been presented as a model). Stationary state voltage-current curves were recorded, and flip-flops were only found in membranes whose hydrodynamic permeability was above a certain value. A theoretical description, agreeing closely with the experimental findings, is given in terms of the Nernst-Planck-Schlögl equations; flip-flops are predicted only if the hydrodynamic permeability is above the fixed ion concentration is below a critical value. These values depend on the hydrostatic pressure and on the ratio of the cation and anion diffusion coefficient in the membrane, and they are found to be far beyond (approximately 3 orders of magnitude) the data for membranes used by others in similar experiments. Although our theoretical analysis demonstrates that the Teorell mechanism is ineligible as a source of excitability in those biological systems for which sufficient data ate available to permit comparison, the membrane properties for which the theory predicts flip-flops are such that it cannot be excluded a priori.

Electric Conductivity↗
PubMed1979

Fetal swallowing and voiding in relation to hydramnios.

Fetal swallowing and voiding were measured using colloidal gold and an ultrasonic scanner, respectively. Subjects in the study were in their 38-40th week of pregnancy. Cases were divided into 3 groups: normal, hydramnios, and oligohydramnios. The normal group had a mean swallowing rate of 198 ml/day and a mean voiding rate of 23.6 ml/hr. No significant differences were found among these rates and the corresponding rates in the other 2 groups. It is concluded that mechanisms other than fetal swallowing and voiding can contribute to the control of amniotic fluid volume at term.

Amniotic Fluid↗
PubMed1976

Bulk flows through human fetal membranes.

Bulk water flows across term human amnio-chorion are studied in vitro. The hydrodynamic permeability is found to vary with both hydrostatic and osmotic pressure. The coefficient characterizing flows generated by hydrostatic pressure is substantially larger than that characterizing osmotic flows. The measurements are utilised to predict in vivo bulk flows across the amnio-chorion. These lead to the prediction that at most a flux of 34-83 ml/day may occur across amnio-chorion directed outwards from the amniotic cavity, the principal contribution to this arising from the effects of hydrostatic pressure.

Amnion↗
PubMedDate not supplied

Uptake of zinc by human placental microvillus border membranes and characterization of the effects of cadmium on this process.

The uptake of Zinc (Zn) by microvillus border membrane vesicles formed from the trophoblast of term human placentae is markedly increased over brief periods of incubation with much slower increases persisting for up to 2 h of incubation. Zinc is both bound to membrane components and transported into intravesicular osmotically active space. Uptake is saturable, temperature dependent from 4 to 37 degrees C with a Q10 of 1.7, and is inhibited by the sulphydryl agent DTNB. About 20 per cent of the uptake is susceptible to inhibition by Cadmium (Cd) at concentrations from 5 to 50 microM, a significant part of the action of this metal being on the transmembrane component of Zn uptake.

Cadmium↗
PubMedDate not supplied

A quantitative study on the effects of maternal smoking on placental morphology and cadmium concentration.

The aim of this study was to quantify the effects of maternal cigarette smoking on placental morphology, paying particular attention to variables known to be influential in facilitating oxygen diffusion. Structural quantities were estimated by stereological analyses of placental samples drawn from non-smoking and smoking women whose smoking habits were assessed both subjectively (from volunteered cigarette consumption) and objectively (by determining levels of plasma cotinine, a major metabolite of nicotine). Concentrations of placental cadmium were also measured. In the smoking group, maternal and fetal haematocrits were elevated and mean birthweight was reduced. Within placentae, the most significant alterations were increases in cadmium levels, the relative volumes of maternal intervillous space, the relative surface areas of fetal capillaries and decreases in the relative and absolute volumes of fetal capillaries. Findings indicate that changes in capillary volume are the result of a decrease in mean capillary diameter rather than total length. The mean thickness of the trophoblast component of the villous membrane was also increased in the smoking group. Although increased haematocrits suggest that fetuses of smoking mothers suffer hypoxic stress, these morphological changes are likely to compromise, rather than assist, transplacental oxygen transfer. This is in marked contrast to the adaptive changes seen in pregnancies associated with preplacental hypoxia and suggests that other factors might be compromising the fetoplacental unit. Finally, although the morphological changes associated with maternal smoking seem to be the result of an all-or-none, rather than dose-dependent, effect, the available evidence is not conclusive.

Cadmium↗