Biomedical subjects

J N Bulmer

Publications and source records attributed to J N Bulmer.

At least 37 records · Page 2Linked to original sources

PubMed2001

Induction of FGF receptor 2-IIIb expression and response to its ligands in epithelial ovarian cancer.

Epithelial ovarian cancers (EOCs) arise in the Ovarian Surface Epithelium (OSE). This tissue is a simple, poorly committed mesothelium which exhibits characteristics of epithelial and mesenchymal cells when grown in culture. In contrast, EOCs frequently exhibit properties of complex epithelial tissues of the female reproductive tract, such as oviductal, endometrial and cervical epithelia, and show induction of expression of epithelial markers such as E-cadherin. Fibroblast Growth Factor Receptor 2 isoform IIIb (FGF receptor 2-IIIb) is a spliced variant of FGF receptor 2 that binds the ligands FGF-1 and FGF-7 with high affinity, and is expressed exclusively by epithelial cells. We have studied the expression of FGF receptor 2-IIIb and its ligands in primary cultures of normal human OSE, EOC cell lines and snap frozen tissue from EOCs. Expression of FGF receptor 2-IIIb mRNA is undetectable in normal OSE, but is expressed in 16/20 (80%) of EOCs. FGFs 1 and 7 mRNAs are expressed in normal OSE, whilst only 4/20 (20%) and 12/20 (60%) of EOCs demonstrated expression for these ligands respectively. However, FGF-7 protein was detected in 70% (mean level=0.7 ng/ml) of ascitic fluids obtained from patients with EOC. FGFs 1 and 7 stimulate DNA synthesis in EOC cell lines that express FGF receptor 2-IIIb. Moreover, DNA synthesis in these cell lines can be partially blocked by blocking antisera to FGFs 1 and 7. It is suggested that induction of expression of FGF receptor 2-IIIb may play a role in the development of EOCs by rendering the OSE susceptible to paracrine and/or autocrine stimulation by its requisite FGF ligands.

Adult↗

PubMed2001

Transforming growth factor-beta expression in human placenta and placental bed in third trimester normal pregnancy, preeclampsia, and fetal growth restriction.

Normal human pregnancy depends on physiological transformation of spiral arteries by invasive trophoblasts. Preeclampsia (PE) and fetal growth restriction (FGR) are associated with impaired trophoblast invasion and spiral artery transformation. Recent studies have suggested that transforming growth factor (TGF)-beta3 is overexpressed in the placenta of PE patients and that this may be responsible for failed trophoblast invasion. There are, however, no studies on TGF-betas in the placenta in FGR or in the placental bed in PE or FGR. In this study we have used immunohistochemistry, Western blot analysis, and enzyme-linked immunosorbent assay to examine the expression of TGF-beta1, TGF-beta2, and TGF-beta3 in placenta and placental bed of pregnancies complicated by PE and FGR and matched control pregnancies. The results show that TGF-beta1, -beta2, and -beta3 are not expressed in villous trophoblasts but are present within the placenta. TGF-beta1, -beta2, and, to a much lesser extent, TGF-beta3 were present within the placental bed but only TGF-beta2 was present in extravillous trophoblast. No changes in expression of either isoform were found in placenta or placental bed in PE or FGR compared with normal pregnancy. These data are not consistent with overexpression of TGF-beta3 being responsible for failed trophoblast invasion in PE. Our findings suggest that the TGF-betas do not have a pathophysiological role in either PE or FGR.

Adult↗

PubMed2001

Human trophoblast invasion and spiral artery transformation: the role of PECAM-1 in normal pregnancy, preeclampsia, and fetal growth restriction.

During early human pregnancy extravillous cytotrophoblasts invade the uterus and spiral arteries transforming them into large vessels of low resistance. Failure of trophoblast invasion and spiral artery transformation occurs in preeclampsia and fetal growth restriction (FGR); these processes are not well understood. Recent studies have suggested that cytotrophoblasts that invade spiral arteries mimic the endothelial cells they replace and express PECAM-1. It was also reported that in preeclampsia, cytotrophoblasts fail to express PECAM-1 and that failure to express endothelial cell adhesion molecules may account for failed trophoblast invasion. Despite the possible importance of adhesion molecules in trophoblast invasion, no study has systematically investigated the expression of PECAM-1 in the placental bed throughout the period of invasion, particularly in the myometrial segments where the key failure occurs. There are no studies on PECAM-1 expression in the placental bed in FGR. We have examined the expression of PECAM-1 in placental bed biopsies and placentas from 8 to 19 weeks of gestation and in the placenta and placental bed in the third trimester in cases of preeclampsia, FGR, and control pregnancies. PECAM-1 was expressed on endothelium of vessels in the placenta and placental bed but not by villous or extravillous trophoblasts in normal or pathological samples. These findings do not support a role for PECAM-1 in normal invasion or in the pathophysiology of preeclampsia or FGR.

Adult↗

PubMed2001

Malaria in pregnancy: adverse effects on haemoglobin levels and birthweight in primigravidae and multigravidae.

BACKGROUND: In areas of endemic transmission, malaria in pregnancy is associated with severe maternal anaemia and low birthweight babies. The prevalence of infection is highest in primigravidae (PG), and hence control efforts are usually geared towards this high risk group. Using a sensitive measure of placental infection, we investigated the relationship between active-acute, active-chronic and past placental infection with maternal anaemia and low birthweight in women of all gravidities. METHODS: Between January 1996 and July 1997, 912 women delivering in Kilifi District Hospital, Kenya, were recruited. Haemoglobin and peripheral malaria slides were taken prior to delivery, placental biopsies and smears were taken at the time of delivery and birthweight and maternal height and weight were measured soon after birth. Information was obtained on socio-economic and educational status. The association between placental malaria, severe anaemia and low birthweight was investigated for women of different gravidities. FINDINGS: By placental histology, the prevalence of active or past malaria in all gravidities was high, ranging from 64% in PG to 30% in gravidities 5 and above. In gravidities 1-4, active malaria infection was associated with severe maternal anaemia, adjusted OR 2.21 (95% CI 1.36, 3.61). There was a significant interaction between chronic or past malaria and severe anaemia in their effects on birthweight, whereby the risk of low birthweight was very high in women with both chronic or past placental malaria and severe anaemia: OR 4.53 (1.19, 17.2) in PG; 13.5 (4.57, 40) in gravidities 2-4. INTERPRETATION: In this area of moderate malaria transmission, women of all parities have substantially increased risk of low birthweight and severe anaemia as a result of malaria infection in pregnancy. The risk of low birthweight is likely to be particularly high in areas with a high prevalence of severe anaemia.

Adolescent↗

PubMed2001

Expression of Fas/Fas ligand by decidual leukocytes in hydatidiform mole.

Complete hydatidiform moles are entirely paternally derived and, therefore, represent a complete intrauterine allograft that might be expected to provoke an altered maternal immune response compared with that of normal pregnancy. Uterine decidua contains a large leukocyte population, of which 10%-20% are T lymphocytes. Fas ligand (FasL) expression by placental trophoblast may induce apoptosis of Fas+ lymphocytes, thereby facilitating immune tolerance and survival of the molar trophoblast. Our previous studies have shown an increase in activated CD4+ decidual T cells in molar pregnancy compared with normal pregnancy. This study was designed to characterize and quantitate Fas/FasL expression by decidual leukocytes in complete and partial hydatidiform mole compared with that in normal early pregnancy using single and double immunohistochemical labeling (i.e., avidin-biotin-peroxidase and avidin-biotin-alkaline phosphatase). A significant increase was found in Fas and FasL expression by decidual CD4+ T cells in complete (Fas+, P = 0.0106; FasL+, P = 0.0081) and partial (Fas+, P = 0.0131; FasL+, P = 0.0051) hydatidiform moles, as was a significant decrease in Fas expression by decidual CD8+ T cells in complete (P = 0.0137) and partial (P = 0.0202) hydatidiform mole compared with normal early pregnancy. The implications of altered Fas/FasL status of decidual T-cell subsets in hydatidiform mole are also discussed.

Antibodies, Monoclonal↗

PubMed2001

Heme oxygenase expression in human placenta and placental bed: reduced expression of placenta endothelial HO-2 in preeclampsia and fetal growth restriction.

In this study we tested the hypothesis that expression of heme oxygenases HO-1 and HO-2, which are responsible for the production of carbon monoxide, are reduced in the placenta and placental bed of pregnancies complicated by preeclampsia (PE) and fetal growth restriction (FGR) compared with control third-trimester pregnancies. Placental protein expression was determined by Western blotting (n=10 in each group) and immunohistochemistry (controls n=18, PE n=19, FGR n=10). Extravillous trophoblast expression was determined by immunohistochemistry of placental bed biopsy samples (controls n=17, PE n=19, FGR n=10). Western blot analysis of placental homogenates showed no overall differences in HO-2 among groups. However, immunohistochemical analysis showed a reduction in HO-2 expression in endothelial cells in both abnormal groups (PE P<0.01; FGR P<0.0005 vs. control group) but no differences in villous trophoblast staining. HO-1 was undetectable by Western blotting in control and abnormal pregnancies and immunoreactivity was very low, suggesting that there is little HO-1 in the placenta. Within the placental bed, HO-2 but not HO-1 was detected on all populations of extravillous trophoblast, but expression of HO-2 or HO-1 did not change in PE or FGR. The reduced expression of HO-2 on endothelial cells in PE and FGR may be responsible for reduced placental blood flow in these conditions. The data do not show changes in HO in the placental bed in PE or FGR.

Adult↗

PubMed2001

Cellular proliferation in the female lower urinary tract with reference to oestrogen status.

OBJECTIVE: To assess cell proliferation throughout the tissues of the female lower urinary tract and to compare cell proliferation rates in women of varying oestrogen status. DESIGN: Prospective observational study. SETTING: A large teaching hospital. SAMPLE: Fifty-nine women undergoing surgery for urogynaecological conditions of whom 23 were premenopausal, 20 were postmenopausal and taking no oestrogen supplementation and 16 were postmenopausal and receiving some form of hormone replacement therapy. Biopsies were taken during surgery from the bladder dome, trigone, the proximal and distal urethra, vagina and vesico-vaginal fascia in the region of the bladder neck. METHODS: Formalin-fixed paraffin-embedded biopsies were labelled by an avidin-biotin technique with a monoclonal antibody raised against part of the nuclear matrix known as Ki-67 antigen. MAIN OUTCOME MEASURES: Ki-67 expression was assessed in the epithelial, subepithelial and muscle or deep fascial regions of all tissues and related to oestrogen status. RESULTS: Ki-67 expression was only found in high levels in biopsies containing squamous epithelia. Significantly higher levels of Ki-67 expression were observed in the tissues of oestrogen replete women in the premenopausal and hormone replacement groups, compared with postmenopausal women receiving no oestrogen supplementation. CONCLUSIONS: Squamous epithelia of the female lower urinary tract exhibit greater levels of cell proliferation in oestrogen replete as compared with oestrogen deficient women. As these same squamous epithelia also consistently express oestrogen receptors, the findings suggest a mechanism by which oestrogen exerts its effect on the lower urinary tract and also provide an explanation for the success of oestrogen in the treatment of some conditions causing lower urinary tract dysfunction in postmenopausal women.

Cell Division↗

PubMed2000

Oestrogen and progesterone receptor expression in the female lower urinary tract, with reference to oestrogen status.

OBJECTIVE: To assess the incidence and distribution of both oestrogen and progesterone receptors throughout the female lower urinary tract, and to compare receptor expression in women of varying oestrogen status. PATIENTS AND METHODS: The study included 90 women undergoing surgery for urogynaecological conditions; 33 were premenopausal, 26 postmenopausal and taking no oestrogen supplementation, and 31 postmenopausal and receiving some form of hormone-replacement therapy. Biopsies were taken during surgery from the bladder dome, trigone, proximal urethra, distal urethra, vagina and vesicovaginal fascia in the region of the bladder neck. All biopsies were routinely fixed and processed for histopathological assessment, and were then labelled immunohistochemically with monoclonal antibodies directed against human oestrogen (NCL-ERLH2) and progesterone (NCL-PGR) receptors. Both oestrogen and progesterone receptor expression were assessed in the epithelial, subepithelial and muscle/deeper fascial regions of all tissue for overall tissue positivity for each receptor, and by semiquantitative analysis of receptor concentration using histochemical scoring of the tissues. RESULTS: Oestrogen receptors were consistently detected in the squamous epithelia and were consistently absent in the urothelial tissues of the lower urinary tract of all women irrespective of oestrogen status; there was no significant variation in histological score. Progesterone receptor expression was more variable, being mostly subepithelial, and significantly lower in postmenopausal women receiving no oestrogen replacement. CONCLUSION: These findings confirm the female lower urinary tract to be a target organ for the action of oestrogen and progesterone, and shed further light on the areas of the lower urinary tract likely to respond to hormone-replacement therapy. This may have implications for the use of oestrogen supplementation in the treatment of lower urinary tract disorders of postmenopausal women.

Biopsy↗

PubMed2000

Hemeoxygenase expression in human placenta and placental bed implies a role in regulation of trophoblast invasion and placental function.

The purpose of this study was to examine the expression of hemeoxygenases HO-1 and HO-2, which are responsible for the production of carbon monoxide (CO), in the human placenta and placental bed and to determine the role of inhibitors of HO on placental perfusion pressure. We hypothesized that HO is expressed within the placenta and that invading cytotrophoblast cells (CTB) express HO isoforms. The expression of HO-1 and HO-2 was studied on placenta and placental bed biopsies, obtained using a transcervical sampling technique, from normal human pregnancies between 8 and 19 wk gestation and at term. In the placenta, HO-2 immunostaining was prominent in syncytiotrophoblast in the first trimester and reduced toward term (P<0.0005). HO-2 endothelial immunostaining was weak in the first trimester, but increased by term (P<0.0005). Within the placental bed, HO-2 was expressed by CTB in cell columns, the cytotrophoblast shell, and cell islands. Both intravascular CTB and interstitial CTB expressed HO-2. HO-1 immunostaining was low in the placenta but intense on the CTB within the placental bed. A striking feature was the absence of HO-1 from the proximal layers of cell columns, with strong expression on the more distal CTB layers of the cell columns. In placental perfusion studies, a significant dose-dependent increase in perfusion pressure was observed in the presence of zinc protoporphyrin, an inhibitor of HO. These results suggest a role for CO in placental function, trophoblast invasion, and spiral artery transformation. Hemeoxygenase expression in human placenta and placental bed implies a role in regulation of trophoblast invasion and placental function.

Blotting, Western↗

PubMed1999

Intermittent sulphadoxine-pyrimethamine to prevent severe anaemia secondary to malaria in pregnancy: a randomised placebo-controlled trial.

BACKGROUND: In areas of endemic transmission, malaria in pregnancy is associated with severe maternal anaemia and low-birthweight babies. We studied the efficacy of intermittent treatment doses of sulphadoxine-pyrimethamine in preventing malaria and severe anaemia in pregnancy in a double-blind placebo-controlled trial among primigravid women living in Kilifi District, Kenya. METHODS: Between January, 1996, and April, 1997, 1264 primigravid women were recruited when they attended for antenatal care, and randomly assigned sulphadoxine-pyrimethamine (640) or placebo (624). Women received one, two, or three doses of study medication depending on the duration of gestation at enrolment. Primary outcome measures were severe anaemia (haemoglobin <8 g/dL) and malaria parasitaemia, assessed at 34 weeks of gestation. Analyses were based on intention to treat among women who had study blood tests at 34 weeks. FINDINGS: 30 (5.3%) of 567 women in the sulphadoxine-pyrimethamine group and 199 (35.3%) of 564 in the placebo group had peripheral parasitaemia (protective efficacy 85% [95% CI 78-90], p<0.0001). 82 (14.5%) and 134 (23.7%) had severe anaemia (protective efficacy 39% [22-52], p<0.0001). Even women who booked late and received only one dose of sulphadoxine-pyrimethamine benefited significantly from the intervention. The effects were seen both in women who owned insecticide-treated bednets and in women who did not. INTERPRETATION: Intermittent presumptive treatment with sulphadoxine-pyrimethamine is an effective, practicable strategy to decrease the risk of severe anaemia in primigravidae living in malarious areas.

Anemia↗

PubMed1999

Human trophoblast invasion and spiral artery transformation: the role of nitric oxide.

During early human pregnancy extravillous cytotrophoblasts invade the uterus and also migrate up the spiral arteries, transforming them into large vessels of low resistance. Failure of transformation has been described in pre-eclampsia, fetal growth restriction, and miscarriage. Recent evidence suggests that some maternal vessels undergo structural changes without interaction with cytotrophoblasts. The possibility arises that local vasoactive mediators such as nitric oxide result in spiral artery dilatation before their invasion. In support of this, a recent histological study in the guinea pig suggested that cytotrophoblasts expressed nitric oxide synthase (NOS) as they surrounded vessels. This study tested the hypothesis that invading cytotrophoblasts express NOS and therefore have the potential to induce vasodilatation by releasing nitric oxide. The expression of NOS on extravillous cytotrophoblasts was studied in placental bed biopsies, obtained, using a transcervical sampling technique, from normal human pregnancies between 8 to 19 weeks of gestation and in the third trimester. Whereas eNOS was expressed by syncytiotrophoblast, neither eNOS or iNOS was expressed by extravillous cytotrophoblasts at any time during invasion. The mechanisms controlling spiral artery transformation are pivotal to understanding normal and abnormal placentation. These results suggest that trophoblast-derived nitric oxide is unlikely to contribute to spiral artery dilatation.

Arteries↗

PubMed1999

Transcervical recovery of fetal cells from the lower uterine pole: reliability of recovery and histological/immunocytochemical analysis of recovered cell populations.

The aim of this work was to isolate, enumerate and attempt the identification of fetal cells recovered from the lower uterine pole. Immediately before elective termination of pregnancy at 7-17 weeks gestation, samples were recovered by transcervical flushing of the lower uterine pole (n = 108) or transcervical aspiration of mucus from just above the internal os (n = 187), and their contents examined using histological, immunohistochemical and molecular techniques. Syncytiotrophoblasts were identified morphologically in 28 out of 89 (31%) and 50 out of 180 (28%) flushings and aspirates respectively (mean 29%). Immunocytochemistry with monoclonal antibodies (mAbs) recognizing trophoblast or epithelial cell antigens on a smaller number of samples (n = 69) identified putative placental cells in 13 out of 19 (68%) and 25 out of 50 (50%) flushings and aspirates respectively (mean 55%). These included groups of distinctive cells with a small, round, hyperchromatic nucleus, strongly reactive with mAbs PLAP, NDOG1 and FT1.41.1. Smaller groups of larger, amorphous cells, usually containing multiple large, pale staining nuclei, reactive with mAb 340 and to a lesser degree with mAb NDOG5 were also observed. Taking cellular morphology and immunophenotype into consideration, the smaller uninucleate cells were likely to be villous mesenchymal cells, while the larger cells were possibly degrading villous syncytiotrophoblast. There was no significant difference in the frequency of fetal cells obtained by the two recovery methods. Squamous or columnar epithelial cells, labelled strongly with antibodies to cytokeratins or human milk fat globule protein, were observed in 97% (29 out of 30) of aspirates. The use of cervagem in a small number of patients prior to termination of pregnancy did not appear to influence the subsequent recovery of placental cells. Y-specific DNA was detected by polymerase chain reaction (PCR) in 13 out of 26 (50%) flushings and (99 out of 154) 64% aspirates analysed (mean 62%). In-situ hybridization (ISH) revealed Y-specific targets in 40 out of 69 (60%) of aspirates analysed. A comparison of PCR data obtained from transcervical recovered samples and placental tissues showed a concordance of 80% (76 out of 95), with 10 false positives. Comparing the PCR data from tissues with data derived by ISH from 41 aspirates gave a concordance of 90% with two false positives. Although syncytiotrophoblasts were much more likely to be present in samples containing immunoreactive placental cells, the detection rates of fetal-derived DNA were similar regardless of the morphological and/or immunological presence of placental cells. We conclude that the transcervical recovery of fetal cells, while promising, requires considerable additional effort being expended in further research and development, particular in the sampling procedure.

Antibodies, Monoclonal↗

PubMed1999

Elevated expression of activation molecules by decidual lymphocytes in women suffering spontaneous early pregnancy loss.

The purpose of this study was to investigate, quantify and compare the expression of activation markers by decidual leukocytes in sporadic spontaneous early pregnancy loss and apparently normal first trimester human pregnancy. Decidua was obtained from 18 therapeutic abortions and 20 sporadic spontaneous abortions at 8-12 weeks gestational age. Cryostat sections were labelled by the avidin-biotin complex-peroxidase method using monoclonal antibodies specific for CD45, CD56, CD3, human leukocyte antigen (HLA) DR, CD69, CD25 and very late antigen (VLA)1. Positive cells were quantified and the results were analysed using the Mann-Whitney statistical test. Significantly increased numbers of CD69-positive and CD25-positive cells were detected in spontaneous abortion decidua, when compared with therapeutic abortion decidua. Approximately 50% of women experiencing spontaneous miscarriage also contained significantly elevated numbers of HLA DR-positive cells within decidua. Double immunohistochemical labelling studies demonstrated that the CD25-positive and CD69-positive cells in spontaneous abortion decidua were CD3-positive T cells rather than CD56-positive granulated lymphocytes. Immunological dysfunction within endometrium may account for a proportion of sporadic spontaneous abortions.

Abortion, Spontaneous↗

PubMed1999

Immunoregulatory activity of decidua in spontaneous early pregnancy loss.

The present study aimed to address whether the immunoregulatory properties of the molecules secreted within decidua were altered in women suffering spontaneous miscarriage, compared with apparently normal fertile women. Unfractionated decidual cells from 22 women undergoing therapeutic pregnancy terminations and 25 women experiencing a sporadic spontaneous early pregnancy loss were isolated, cultured for 24 h and 72 h, and supernatants were collected. The effect of decidual supernatants on phytohaemagglutinin (PHA)-induced peripheral blood lymphocyte proliferation was investigated. Immunosuppressive activity was detected in 24 h cell culture supernatants from 91% of therapeutic abortion cases compared with only 64% of spontaneous abortion samples; 72 h supernatants from all of therapeutic abortion samples and 90% of spontaneous abortion cases suppressed lymphoproliferation. The remaining spontaneous abortion samples (36% of 24 h supernatants; 10% of 72 h supernatants) enhanced or had no effect on lymphocyte proliferation. Enhancement of lymphocyte proliferation was not observed in therapeutic abortion samples, and the association between stimulation of cell proliferation and spontaneous abortion was significant for 24 h decidual cell supernatants at 50% concentration (P = 0.02). These findings suggest that in a subgroup of women experiencing spontaneous early pregnancy loss, soluble factors within decidua display altered immune responses that may be implicated in the complex process of fetal rejection.

Abortion, Spontaneous↗

PubMed1999

Phenotypic analysis and proliferative responses of human endometrial granulated lymphocytes during the menstrual cycle.

The in vivo function of the unusual population of CD56+ CD16- endometrial granulated lymphocytes (eGLs) in human endometrium is unknown; their increased numbers in the secretory phase of the menstrual cycle suggests that they may play a role in the immunobiology of nonpregnant endometrium. In the present study, the phenotype and proliferative responses of eGLs at various phases of the menstrual cycle were compared with those in early pregnancy. Endometrial GLs were highly purified (> 98% CD56+) using immunomagnetic separation, and the expression of cell surface antigens was examined in smears using a double immunohistochemical labeling technique. Proliferative responses to mitogens and interleukin 2 (IL-2) were assessed in hanging drops in 60-well Terasaki plates. There was low to no expression of CD3, CD8, CD16, HML-1, L-selectin, and CD25 (IL-2 receptor alpha) on CD56+ cells isolated from nonpregnant and pregnant endometrium. The expression of CD2, CD49a, and CD122 (IL-2 receptor beta, IL-2Rbeta), however, increased from the proliferative to the late secretory phase of the menstrual cycle. In contrast, CD11a, CD69, and CD49d expression was high and did not vary with menstrual cycle phase; CD49d levels were significantly reduced in early pregnancy. Unlike early-pregnancy eGLs, none of the CD56+ eGL cultures throughout the menstrual cycle displayed phytohaemagglutinin (PHA)-induced lymphoproliferation. In contrast, eGLs from nonpregnant endometrium in the presence of 5 or 100 U/ml IL-2 after 48- and 120-h incubation showed significant proliferative responses, as did eGL cultures from early pregnancy. A significantly reduced number of proliferative phase eGL cultures proliferated in response to IL-2 compared to secretory phase and early-pregnancy eGL cultures. The IL-2-induced proliferative responses of CD56+ eGLs were associated with increased IL-2Rbeta (CD122) expression. These findings demonstrate 1) differential eGL expression of CD2, CD49a, and CD122 during the menstrual cycle; 2) differential IL-2-induced eGL proliferative responses during the menstrual cycle; and 3) differences between eGLs from nonpregnant and pregnant endometrium in CD49d expression and their ability to respond to PHA.

Antigens, CD↗

PubMed1999

Up-regulation of natural killer cell cytotoxicity by interleukin-2: the effect of sex and parity.

PROBLEM: Peripheral blood lymphocytes (PBLs) from some, but not all, female donors showed increased cytotoxicity in response to interleukin (IL)-2. METHOD OF STUDY: The effect of IL-2 on natural killer (NK) cell cytotoxicity was compared in nulliparous females, parous females, and males. Peripheral blood lymphocytes were preincubated for 20 or 72 hr with 5 or 100 U/ml IL-2 and cytotoxicity against K562 targets was then examined. RESULTS: In the parous females, only the 72-hr preincubation with 100 U/ml IL-2 significantly increased NK cell cytotoxicity, whereas nulliparous females also showed significantly increased cytotoxicity after a 20-hr preincubation with 100 U/ml IL-2. Neither female subject group had increased activity after preincubation for 20 or 72 hr with 5 U/ml IL-2. However, male peripheral blood lymphocytes also showed a significant increase in NK cell cytotoxicity when preincubated for 72 hr with 5 U/ml IL-2. CONCLUSIONS: The effect of IL-2 on NK cell cytotoxic activity may be related to sex and the state of parity.

Adult↗

PubMed1999

Decidual T lymphocyte activation in hydatidiform mole.

AIM: To quantify and compare decidual leucocyte subpopulations in complete and partial hydatidiform molar pregnancy with those in normal early pregnancy. METHODS: Decidual leucocytes were characterised using an avidin-biotin technique and a panel of monoclonal antibodies in formalin fixed, paraffin embedded decidual tissues from 10 normal first trimester pregnancy terminations and from 13 partial and 13 complete hydatidiform moles. Immunostained cells were fully quantitated and differences between subject groups were analysed using the Mann-Whitney test. T lymphocyte populations were further characterised using double immunohistochemical labelling. RESULTS: The numbers and percentages of CD3+ and CD4+ T cells were significantly increased in complete hydatidiform moles compared with partial moles and normal early pregnancy decidua. No differences were found in the number or percentage of CD8+ T cells. The CD8+ to CD4+ T cell ratio decreased significantly in complete mole compared with partial mole and normal decidua. The numbers and percentages of CD45RO+ cells increased significantly in both partial and complete hydatidiform mole compared with normal first trimester decidua. Double labelling confirmed that 50% of CD3+ T cells in complete and partial molar pregnancy coexpressed CD45RO, compared with 30% in normal pregnancy. Other leucocyte populations (eGLs, macrophages, B cells, and classical natural killer cells) did not differ between complete and partial mole and normal pregnancy decidua. CONCLUSIONS: The presence of an increased population of activated decidual CD45RO+ T cells in complete and partial molar pregnancy suggests altered maternal immune responses against molar trophoblast.

CD4 Lymphocyte Count↗

PubMed1998

Characterization of tubal and decidual leukocyte populations in ectopic pregnancy: evidence that endometrial granulated lymphocytes are absent from the tubal implantation site.

OBJECTIVE: To compare and quantify leukocyte populations at the tubal implantation site, in the tubal mucosa away from the implantation site and in the intrauterine decidua in women who have had an ectopic tubal pregnancy with leukocyte populations in the decidualized endometrium in women who have had a normal intrauterine pregnancy. DESIGN: Retrospective immunohistochemical study. SETTING: Department of Pathology, University of Newcastle, Royal Victoria Infirmary, Newcastle upon Tyne, Tyne and Wear, United Kingdom. PATIENT(S): Paraffin-embedded tissue blocks from 30 women who had had an ectopic pregnancy (EP) and control tissue blocks from 19 women who had undergone elective first trimester pregnancy termination. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Quantitative analysis of defined leukocyte subpopulations in the fallopian tube (at the implantation site and in the tubal mucosa away from the implantation site) and intrauterine decidua. RESULT(S): Endometrial granulated lymphocytes were absent from both the tubal mucosa away from the implantation site and the tubal implantation site. T lymphocytes and macrophages formed the predominant leukocyte subpopulations in both tubal areas. In the intrauterine decidua from women who had had an EP, endometrial granulated lymphocytes were the most abundant leukocyte population and macrophages and T cells formed the second and third major leukocyte subpopulations, respectively. No differences were detected in the number or proportion of these decidual leukocytes in women who had had a normal pregnancy vs. in those who had had an EP. CONCLUSION(S): The absence of endometrial granulated lymphocytes from the tubal implantation site suggests that the local presence of the cells is not essential for implantation and early placental development events.

Antibodies, Monoclonal↗