School of Paediatrics & Reproductive Health

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Tissue oxygenation and red cell 2,3-diphosphoglycerate in normal and abnormal pregnancy
(Blackwell Science, 1976) MacLennan, A.H.; Emerson, P.M.; Hunter, D.J.S.; Darley, J.H.
Maternal tissue oxygenation was reflected by the level of red cell, 2,3-diphosphoglycerate (DPG) was measured before, during and after normal pregnancy. Following an initial fall at the beginning of pregnancy there was a significant rise in the mean level of DPG during pregnancy with an abrupt fall in the puerperium. The mean red cell DPG level in the third trimester of pregnancies complicated by pre-eclampsia and diabetes was not statistically different from the normal but the mean value of all pregnancies in which the fetus was stillborn or growth retarded was significantly lower (p less than 0-001). The possible mechanism of the changes in normal and abnormal pregnancy is discussed and it is suggested that the measurement of red cell DPG in the third trimester of pregnancy may prove to be a useful parameter of placental oxygenation.
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Goals and potential value of alternative teratogenicity tests
(Karger, 1985) Kochhar, D.; Hickey, T.
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Serum relaxin and pelvic pain of pregnancy
(Elsevier Science, 1986) Maclennan, A.; Green, R.; Nicolson, R.; Bath, M.
Serum relaxin immunoreactivity was measured by means of a porcine relaxin radioimmunoassay in 35 patients with severe pelvic pain and pelvic joint instability during late pregnancy. Results were compared with a control group of 368 samples obtained throughout pregnancy from normal singleton pregnancies. Most of the relaxin concentrations in the study group were above the 95% confidence limits of the median for the corresponding gestational age in the control group. The difference in relaxin levels between the study and control groups in the third trimester was highly significant. Relaxin levels in patients with pelvic pain were close to normal non-pregnant levels by the third postnatal day. The highest relaxin levels during pregnancy were found in the patients who were the most incapacitated clinically. The results suggest that there may be an association between high serum relaxin levels and pelvic pain and joint laxity during late pregnancy.
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Serum relaxin in pregnancy
(Elsevier Science, 1986) Maclennan, A.; Nicolson, R.; Green, R.
Serum relaxin immunoactivity was measured by means of a porcine radioimmunoassay in a cross-sectional study of 302 normal singleton pregnancies. Concentrations in the third trimester were lower than in early and mid pregnancy. At term, relaxin levels in patients who went into spontaneous labour within a week of sampling were significantly lower than in those who did not. However, relaxin levels were highest during labour and fell almost to non-pregnant levels by the third postnatal day. Levels in twin pregnancies in the third trimester were higher than those in singleton pregnancies. Serial samples from 4 patients with a history of premature labour showed declining, very low levels in the only patient who subsequently had a preterm delivery. These results are compatible with the proposed roles of relaxin during pregnancy: namely, to maintain myometrial quiescence, facilitate uterine stromal remodelling during uterine growth, and promote cervical ripening at the onset of parturition.
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Zellweger syndrome amniocytes - morphological appearance and a simple sedimentation method for prenatal-diagnosis
(Springer Nature, 1988) LAZAROW, P.B.; SMALL, G.M.; SANTOS, M.; SHIO, H.; MOSER, A.; MOSER, H.; ESTERMAN, A.; BLACK, V.; DANCIS, J.
Zellweger syndrome is the prototype of a growing group of genetic diseases caused by an absence or deficiency of peroxisomes. The defect causes the enzyme catalase to remain in the cytosol instead of being packaged into peroxisomes. This mislocalization can be easily detected by sedimentation analysis. Amniocytes were homogenized and then centrifuged to pellet organelles. Catalase was found to sediment with the peroxisomes in the homogenates of normal cells, but to remain in the supernatant with Zellweger syndrome amniocyte homogenates. This striking difference is unambiguous and reproducible, and provides a simple method for prenatal diagnosis. Moreover, it allows one to differentiate diseases in which peroxisomes are deficient from other peroxisomal diseases in which the organelle is intact, but one enzyme is defective. Electron microscopic observations support the biochemical determinations. Normal amniocytes contain small peroxisomes in which a weak cytochemical reaction for catalase may be demonstrated. Zellweger amniocytes appear to lack these organelles, although some cells have rare structures that might be residual or abnormal peroxisomes.
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Granulocyte macrophage colony stimulating factor (GM-CSF) in the murine reproductive tract: stimulation by seminal factors
(CSIRO Publishing, 1990) Robertson, S.A.; Seamark, R.F.
The activity of GM-CSF during early pregnancy in the murine uterine lumen in vivo and in media conditioned by uterine cells in vitro has been assessed. GM-CSF was detected in uterine luminal fluid recovered by lavage on the morning after syngeneic mating (median level 5.7 CFUc U/uterus) and following mating with vasectomized (5.1 U/uterus) or allogeneic males (4.4 U/uterus), with significantly lesser (P less than 0.05) amounts recovered from the uteri of superovulated, mated mice. By contrast, GM-CSF was only detectable (greater than 0.5 U/uterus) in the luminal fluid of three of 22 unmated oestrous mice examined. No activity was detected in secretions from male accessory glands including seminal vesicle, epididymis, prostate and coagulating gland (less than 0.5 U/gland). GM-CSF was found at higher levels in supernatants from cell monolayers prepared by tryptic digest of the uteri of Day 1 mated mice than those from unmated oestrous mice (P less than 0.05). Little GM-CSF was detected in supernatants from ovariectomized mice. An alpha-GM-CSF polyvalent antibody neutralized the FD5/12 bioassay response confirming the identity of the lymphokine. The interleukins IL-2 and IL-3 were not detected in uterine luminal fluid nor in media conditioned by cell monolayers. We postulate that elevated uterine GM-CSF activity after mating is elicited by a non-sperm associated, non-MHC component of the ejaculate and synthesized by a hormone-responsive endometrial cell population. This cytokine may have an embryotrophic role or contribute to priming of the uterus for implantation.
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Lymphokines, including interleukin-2, alter gonadotropin-stimulated progesterone production and proliferation of human granulosa-luteal cells in vitro
(Endocrine Society, 1991) Wang, L.; Robertson, S.A.; Seamark, R.F.; Norman, R.J.
The effects of human interleukin-1 (IL-1) and IL-2 on human granulosa-luteal cell progesterone production were examined with or without hCG stimulation in vitro. Human granulosa-luteal cells were recovered from follicular fluid obtained from women undergoing in vitro fertilization procedures and cultured for up to 7 days before supernatant progesterone level measurement. Lymphokine-rich conditioned medium was prepared from mitogen-stimulated human peripheral blood leukocytes (HPL-CM). The influence of HPL-CM on both granulosa-luteal cell progesterone production and cell growth was inhibitory. In contrast, supernatants of the IL-2-producing cell line MLA-144 (MLA-CM) stimulated both basal progesterone secretion and cell proliferation. Human recombinant IL-2 (from 0.1-100 IU) alone did not change progesterone levels, compared to control values, after 24 h of cell culture. However, 1, 10, and 100 IU IL-2 significantly inhibited progesterone secretion from cells stimulated by 5 IU hCG (P less than 0.01). The enhanced progesterone levels stimulated by forskolin were also significantly inhibited by 10 IU IL-2 (P = 0.01). This effect was not mediated through decreased cAMP, since the forskolin-enhanced cAMP level was not influenced by IL-2, IL-1, with or without hCG, did not show any effect on progesterone production during either 24 or 48 h of cell culture. It is concluded that 1) human recombinant IL-2 significantly inhibits progesterone production stimulated by hCG in human granulosa-luteal cells; 2) IL-2 also had a marked inhibitory effect on forskolin-induced progesterone release, but did not influence the increased cAMP level stimulated by forskolin; 3) the inhibitory influence of IL-2 on progesterone synthesis may be down-stream in the signal transduction pathway from cAMP activation; and 4) HPL-CM and MLA-CM produced inhibitory and stimulatory effects, respectively, on both basal and hCG-stimulated progesterone levels as well as on granulosa-luteal cell proliferation. These activities cannot be completely attributed to IL-2, and other mediators of leukocyte origin may, therefore, exist.
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Determination of the optimal ratio of linoleic acid to α-linolenic acid in infant formulas
(Elsevier, 1992) Clark, K.J.; Makrides, M.; Neumann, M.A.; Gibson, R.A.
The fatty acid composition of erythrocyte total lipids taken from a group of term infants 10 weeks after being fed a commercial infant formula with a high ratio of linoleic acid (18:2n-6) (LA) to alpha-linolenic acid (18:3n-3) (ALA) (19:1; LA, 14%; ALA, 0.7%; group A, n = 10) was compared with the fatty acid composition of erythrocytes from infants fed formulas that contained LA/ALA ratios reduced by either increasing ALA (4:1; LA, 13%; ALA, 3.3%; group B, n = 11) or decreasing LA (3:1; LA, 3.5%; ALA, 1.1%; group C, n = 8). Results were compared with those in an age-controlled group (n = 9) of breast-fed infants. Decreasing the LA/ALA ratio increased n-3 C20 and C22 fatty acid incorporation (formula B = 8.98% +/- 0.65%; formula C = 9.30% +/- 0.95%) relative to formula A (5.97% +/- 0.76%; p less than 0.05). Although docosahexaenoic acid (22:6n-3) (DHA) incorporation was highest in infants fed formulas B and C (4.78% +/- 0.45% and 4.48% +/- 0.49%, respectively) relative to formula A (3.47% +/- 0.46%; p less than 0.05), it did not reach levels found in breast-fed infants (6.55% +/- 1.23%; p less than 0.05). In addition, levels of arachidonic acid (20:4n-6) (AA) were lower in all formula-fed groups (p less than 0.05) relative to those in breast-fed infants. Based on some equations, it is predicted that AA levels in tissues of infants fed lower LA/ALA ratios would be reduced even further. Because both AA and DHA are probably essential for normal neural development of the infant, formulas with LA/ALA ratios below 4:1 are likely to result in fatty acid profiles notably different from those of breast-fed infants.
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Granulocyte-macrophage colony stimulating factor (GM-CSF): one of a family of epithelial cell-derived cytokines in the preimplantation uterus
(CSIRO Publishing, 1992) Robertson, S.A.; Seamark, R.F.
Granulocyte-macrophage colony stimulating factor (GM-CSF) is one of a number of lympho-haemapoietic cytokines, including CSF-1, interleukin-6 (IL-6) and leukaemia inhibitory factor (LIF) now known to be synthesized by epithelial cells in the murine uterus. GM-CSF synthesis is regulated primarily by the ovarian steroid hormone oestrogen, but is also subject to modulation by factors including a seminal component of seminal vesicle origin which stimulates a 20-fold increase in luminal fluid content at mating, and bacterial lipopolysaccharide (LPS) and the T-lymphocyte and natural killer (NK) cell product interferon-gamma (IFN gamma). In the non-pregnant mouse GM-CSF synthesis peaks at oestrus. Synthesis is maintained at comparable or moderately higher levels during the preimplantation period of pregnancy and in the non-decidualized endometrium during mid gestation. An embryotrophic activity is suggested by studies in vitro that indicate that GM-CSF stimulates attachment and outgrowth of blastocysts. It is postulated that GM-CSF is of major importance to the physiology of pregnancy through its role as a component of a local cytokine circuit acting to recruit and regulate function of endometrial leukocytes, and by its action as interlocutor and important effector arm in embryo-maternal interactions during gestation.
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Uterine epithelial cells synthesize granulocyte-macrophage colony-stimulating factor and interleukin-6 in pregnant and nonpregnant mice
(Society for the Study of Reproduction, 1992) Robertson, S.A.; Mayrhofer, G.; Seamark, R.F.
Cytokine secretion by endometrial cells from estrous and mated mice was measured using specific bioassays. The granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-6 (IL-6) contents of uterine intraluminal fluid were elevated greater than 20-fold and 250-fold respectively following mating, and both cytokines were synthesized in abundance in vitro by uterine cells harvested at estrus and on Day 1 of pregnancy. Synthesis was not impaired in genetically lymphocyte-deficient nude, SCID, or beige mice. To determine the cellular origin of the cytokines, a panning technique employing monoclonal antibodies against a range of leukocyte and other lineage markers was used to isolate uterine cell subsets in vitro. These experiments identified glandular and/or luminal epithelial cells as the major source of GM-CSF and IL-6 in estrous and pregnant uteri. Stromal fibroblasts also synthesized IL-6, as did macrophages in mated mice. Epithelial cells harvested from midgestation uteri secreted GM-CSF and IL-6 in quantities similar to those of cells from estrous and mated mice. Bioactivities of both cytokines derived from epithelial cells were neutralized by specific antibodies, and size-exclusion chromatography of conditioned media from uterine cells revealed peaks of GM-CSF and IL-6 bioactivity with M(r) 23,000 and 23,000-26,000, respectively. Bioassay of luminal fluids and culture supernatants were negative for the cytokines interleukin-1, interleukin-2, interleukin-3, and tumor necrosis factor-alpha. These studies identify murine uterine epithelium as a potent source of the cytokines GM-CSF and IL-6, which we postulate have potentially important functions in pregnancy through actions on target cells in both the uterus and the conceptus.
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Cytokines in rodent reproduction and the cytokine-endocrine interaction
(Current Biology, 1992) Robertson, S.A.; Brannstrom, M.; Seamark, R.F.
Insights derived from recent studies employing rodent models demonstrate that the synthesis of pluripotent cytokines is an important function of resident cells in the female reproductive tract. Through steroid hormone regulated secretion of these mediators, resident cells appear to coordinate the recruitment and action of leukocytes that are centrally implicated in the dramatic remodelling processes characteristic of reproductive events.
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Localization of leukocyte subsets in the rat ovary during the periovulatory period
(Society for the Study of Reproduction, 1993) Brannstrom, M.; Mayrhofer, G.; Robertson, S.A.
The ovulatory process has been compared with inflammation because several classical inflammatory mediators appear to participate in this process. One component of the inflammatory reaction is the migration of leukocytes to the site of inflammation and the subsequent activation of these cells. We have reported recently that perfusion of leukocytes into the rat ovary in vitro enhances the number of LH-induced ovulations, which suggests an active role of leukocytes in ovulation. In the present study we characterize immunohistochemically the distribution of macrophages, T lymphocytes, and granulocytes in the ovaries of untreated immature rats and of eCG-hCG-primed rats killed prior to hCG injection, at ovulation, and at 33-36 h post-ovulation. Macrophages, identified with monoclonal antibodies ED1 and ED2, were the major leukocyte population and were found primarily in the medullary region surrounding the blood vessels. The density of the cells in this region increased continuously during development to sexual maturity and until after ovulation. Macrophages were also present in the thecal layer of the preovulatory follicles, and the numbers of these cells increased about 5-fold in this area in ovulating follicles (12 h after hCG) compared to preovulatory follicles (before hCG). A portion of macrophages in both areas expressed major histocompatibility complex (MHC) class II antigens (OX6+); these cells were present mostly in the medullary region, with no apparent change in density during the periovulatory period. Neutrophilic granulocytes comprised a lesser proportion of the total leukocyte population in the medullary region but were abundant in the thecal layer. The density of neutrophils increased 3-fold in the medullary region and 8-fold in the thecal region in ovulatory compared to preovulatory follicles. T lymphocytes (OX52+) were evenly distributed at relatively low density in the medulla and the stroma of the cortex. Most T lymphocytes expressed the CD8 antigen (OX8+) and hence were of the MHC class I-restricted phenotype. Few T lymphocytes were present in the thecal layer. In summary, macrophages, neutrophilic granulocytes, and T lymphocytes are present in the ovary at ovulation. There is a selective increase in the numbers of macrophages and neutrophilic granulocytes in the medullary region and in the thecal layer as the ovulatory period progresses, indicating that these cells may actively be involved in the tissue remodeling occurring at ovulation.
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The trophoblast as an integral component of a macrophage-cytokine network
(Nature Publishing Group, 1993) Guilbert, L.; Robertson, S.A.; Wegmann, T.G.
The trophoblast, an epithelial cell of fetal origin that forms the physical barrier between the mother and developing conceptus, becomes a component of the host immune system during pregnancy. Of the classical immune cells, it most closely resembles the macrophage, also present in high numbers in the pregnant uterus. The macrophage and trophoblast, as cell classes, share characteristics such as phagocytosis, cyncytialization, invasiveness, expression of the proteins CD4, CD14, IgG receptor (FcR), non-specific esterase, granulocyte macrophage-CSF (GM-CSF), colony stimulating factor 1 (CSF-1), interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor (TNF-α), transforming growth factors (TGF), platelet-α derived growth factor (PDGF) and receptors for these cytokines. In the uterus both cell types appear regulated by a common element, the uterine epithelium, that secretes cytokines such as CSF-1, GM-CSF, TNFα, TGFβ, IL-6, and leukaemia inhibitory factor (LIF) that target both macrophages and trophoblasts. The common characteristics and regulation that make teleological sense in terms of co-ordinating local uterine immunity during pregnancy may also be important in transmission of congenital diseases such as AIDS. The production by the uterine epithelium of a number of cytokines previously only associated with mononuclear phagocyte production and function predicts the existence of a similar, but broader, shared cytokine network encompassing trophoblast and the principal immune regulatory cell, the T lymphocyte.
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Erythrocyte docosahexaenoic acid correlates with the visual response of healthy, term infants
(International Pediatric Research Foundation, 1993) Makrides, M.; Simmer, K.; Goggin, M.; Gibson, R.A.
Recent studies have reported that formula-fed preterm infants score lower on visual and developmental tests relative to breast-fed preterm infants. This phenomenon has been associated with the presence of docosahexaenoic acid (DHA), an omega-3 fatty acid, in breast milk and its absence from infant formula. To investigate the possibility that DHA status of healthy, term infants is also related to neuronal function of the visual pathway, we studied the erythrocyte fatty acid profiles of 16 infants at 22.3 +/- 3.9 wk of age and related these to maturity of the visual pathway as assessed by visual-evoked potentials. Healthy, term infants fed breast milk had better visual-evoked potential acuity (p < 0.05) and higher DHA levels (p < 0.001) than infants who received infant formula as their major energy source. There was a positive correlation between erythrocyte DHA and visual-evoked potential acuity (p < 0.01). The data are preliminary and the long-term effects as yet unknown. However, our results suggest that there is an urgent need to evaluate the dietary fatty acid supply of formula-fed term infants.
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Leukocyte subpopulations in the rat corpus luteum during pregnancy and pseudopregnancy
(Society for the Study of Reproduction, 1994) Brannstrom, M.; Giesecke, L.; Moore, I.C.; van den Heuvel, C.J.; Robertson, S.A.
Leukocytes including monocyte/macrophages, granulocytes, and T lymphocytes were localized in the corpus luteum (CL) of pregnant and pseudopregnant rats using monoclonal antibodies reactive with lineage-specific antigens. Neutrophilic granulocytes and monocytes/macrophages were found to be the most abundant leukocyte populations in the CL during both pregnancy and pseudopregnancy. The density of neutrophilic granulocytes (MCA 149-reactive cells) increased approximately 2-fold after mating, to peak on Day 9 of pseudopregnancy (214 +/- 13 positive cells/0.125 mm2 grid area) and Day 10 of pregnancy (216 +/- 12/grid area), and then declined in later stages of CL life. In pregnant rats, monocytes/macrophages positive for the monoclonal antibody ED1 were most numerous during early CL life when they were approximately 6-fold more plentiful than at luteolysis (153 +/- 14/grid area at Day 5 vs. 25 +/- 2 at 2 days postpartum). In pseudopregnant rats, the density of ED1-positive cells declined approximately 5-fold during the life span of the CL (124 +/- 17/grid area at Day 2 vs. 20 +/- 2 at Day 13) prior to a second, somewhat lesser peak at luteal regression (84 +/- 12 at Day 15). Fewer monocyte/macrophages within the CL were found to express antigen reactive with the monoclonal antibody ED2, which is characteristically a marker for tissue-macrophages (7% of the density of ED1-positive cells at Day 5 in the pregnant group and 13% at Day 2 in the pseudopregnant group); and while there was an approximately 60% reduction in the number of ED2-positive cells during pregnancy, these cells were found not to fluctuate significantly in number over the course of CL life in pseudopregnant animals.In contrast, the number of major histocompatibility complex class II (OX6)-reactive cells increased approximately 4.5-fold and 2.5-fold in pseudopregnant and pregnant rats, respectively, suggesting that luteal regression is accompanied by enhanced macrophage activation. T lymphocytes (OX52- positive cells) were found to have a consistently sparse distribution within the CL (1% of the density of ED₁-positive cells at Day 5 in the pregnant group and 2% at Day 2 in the pseudopregnant group). These data indicate that leukocytes of the myeloid lineages comprise substantial and dynamic populations within the rat CL, and suggest that these cells may have roles both in regulating steroidogenesis and in the tissue remodeling that accompanies CL development and demise during pregnancy.
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Isolation and characterization of ovine IGFBP-4: protein purification and cDNA sequence
(BioScientifica, 1994) CARR, J.M.; GRANT, P.A.; FRANCIS, G.L.; OWENS, J.A.; WALLACE, J.C.; WALTON, P.E.
Three different molecular mass forms of IGF-binding proteins (IGFBPs) were purified from ovine plasma by IGF-I affinity chromatography and reverse-phase HPLC: a 46 kDa doublet and 29 kDa and 24 kDa forms. Amino-terminal sequence analysis confirmed that these proteins were ovine (o)IGFBP-3 (46 kDa) and two molecular size variants of oIGFBP-4. oIGFBP-3 and the 29 kDa form of oIGFBP-4 were shown to be N-glycosylated. Isoelectric points were determined to be at approximately pH 6 for oIGFBP-3 and at pH 7 and pH 7.5 for the 29 and 24 kDa forms of oIGFBP-4 respectively. The two different molecular mass variants of oIGFBP-4 had similar IGF-binding properties. Compared with human IGFBP-3 and oIGFBP-3, the two variants of oIGFBP-4 exhibited lower relative binding to amino-terminally modified IGF-I analogues in a competitive IGF-binding assay. The full protein sequence of oIGFBP-4, as deduced from the cDNA sequence, showed a high degree of identity with rat (90%), human (96%) and bovine (98%) IGFBP-4. The cDNA sequence also showed homology over regions of the 3' non-coding sequence, particularly in comparison with bovine IGFBP-4 (96%). Northern analysis of mRNA for oIGFBP-4 indicated a 2.6 kb major transcript and two minor transcripts of approximately 2.1 and 1.8 kb. oIGFBP-4 mRNA transcripts were detected in adult ewe liver > kidney > lung >> heart and also in several fetal tissues, thus suggesting tissue-specific and developmental regulation. The availability of purified oIGFBP-4 and oIGFBP-3 as well as DNA probes for oIGFBP-4 will enable further study of the properties and functions of these proteins, as well as the establishment of specific assays for these IGFBPs.
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Rat ovary produces cytokines during ovulation
(Society for the Study of Reproduction, 1994) Brannstrom, M.; Norman, R.J.; Seamark, R.F.; Robertson, S.A.
To examine the production of cytokines by the ovary during ovulation, ovaries were obtained from immature rats and from eCG/hCG-primed immature rats at different stages of the ovulatory process (before hCG injection, 10 h after hCG, and 20 h after hCG) and were perfused in vitro for 5 h. Large quantities of interleukin (IL)-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) bioactivity and smaller amounts of tumor necrosis factor-alpha (TNF alpha) and IL-1 bioactivity were found in the perfusate. IL-2 and IL-3 were not detectable in the perfusion media. The GM-CSF content was significantly higher in the perfusate of ovulating ovaries (obtained 10 h after hCG) compared to the earlier stages. Studies on preovulatory ovaries (prior to hCG injection) revealed that GM-CSF release was not influenced by LH, but was markedly increased when recombinant human IL-1 beta (4 ng/ml) was added to the perfusion medium. IL-6 was released in similar amounts from ovaries at all stages. The identity of bioactive GM-CSF was confirmed by neutralization with a specific polyclonal antibody against murine GM-CSF. Size-exclusion chromatography of perfusion medium revealed peaks of GM-CSF and IL-6 bioactivity at approximate molecular masses of 21-23 kDa and 24-25 kDa, respectively. This study demonstrates that the rat ovary produces IL-6, GM-CSF, TNF alpha, and IL-1 prior to and during the ovulatory process and that there are temporal fluctuations in GM-CSF release with a peak in output at ovulation.
Open Access
Cytokine receptor expression in human lymphoid tissue: analysis by fluorescence microscopy
(Hindawi Publishing Corporation, 1994) Zola, H.; Ridings, J.; Weedon, H.; Fusco, M.; Byard, R.; Macardle, P.
A highly-sensitive flourescence method, capable of detecting cytokine receptors present at low concentrations (around I DO molecules per cell) by flow cytometry, was adapted for use on tissue sections. This method was used to examine the expression of several cytokine receptors in lymphoid ti ss ues. lL-2 receptors were distributed broadly, with higher concentrations in T cell areas. lL-1 receptor Type I was detected in T cell areas and in the follicular mantle, and was strongly expressed on vasc ular endothelium. IL-6 receptor was found at very low concentration, both within and outside germinal centres. The gp 130 molecule, which is involved in the functional receptor complex for IL-6 and several other cytokines, was present at higher concentrations, particularly in the germinal centre. Analysis of receptor expression in secondary lymphoid tissue provides evidence bearing on the physiological roles of cytokines, as these tissues contain cells at various stages of physiological activation located in well-defined functional zones.
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Paediatric surgery in Cambodia
(Australasian Medical Pub. Co., 1995) Dewan, Paddy A.
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Improving diagnosis of Huntington's disease by analysis of an intragenic trinucleotide repeat expansion
(Australasian Medical Pub. Co., 1995) Firgaira, F.; Turner, D.; Haan, E.; Suthers, G.

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