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Biomedical subjects

B Thilaganathan

Publications and source records attributed to B Thilaganathan.

At least 73 records · Page 4Linked to original sources

Neutrophil and monocyte beta 2-integrin expression in maternal and fetal blood.

OBJECTIVE: The aim of this study was to investigate fetal and maternal leukocyte beta 2-integrin expression throughout pregnancy. STUDY DESIGN: In a cross-sectional study of 173 fetuses at 18 to 40 weeks' gestation, 114 women with normal singleton pregnancies at 6 to 40 weeks, and 25 adult volunteers, flow cytometry was used to determine neutrophil and monocyte expression of beta 2-integrins. RESULTS: The surface density of beta 2-integrins on fetal neutrophils and monocytes increased significantly with gestation, except for the expression of fetal monocyte CD11b, which did not change. There were no significant changes in maternal beta 2-integrin expression with gestation. During the third trimester fetal expression of CD18, CD11b, and CD11c on neutrophils and CD11b on monocytes was lower, and maternal expression of CD11a on neutrophils and CD18, CD11a and CD11c on monocytes was higher than were the control adult values. CONCLUSIONS: These data demonstrate that pregnancy is associated with changes in the expression of maternal beta 2-integrins and illustrate the pattern of immunophenotypic maturation of fetal beta 2-integrins on neutrophils and monocytes.

CD11 Antigens↗

Altered band 3 structure and function in glycophorin A- and B-deficient (MkMk) red blood cells.

The anion transport activity of the human erythrocyte anion transporter (band 3; AE1) has been examined in both normal and glycophorin A (GPA)-deficient (MkMk) human red blood cells (RBCs). The sulfate transport activity of MkMk cells (from two ethnically diverse sources) was approximately 60% that of normal erythrocytes under the transport assay conditions used. However, MkMk and normal RBCs contained similar amounts of band 3. The reduction in sulfate transport activity was shown to be caused by an increase in the apparent Km for sulfate in MkMk RBCs, suggesting the band 3 in the MkMk RBCs has a lowered binding affinity for sulfate anions. The size of the N-glycan chain on band 3 of the MkMk cells was larger than that on band 3 from normal RBCs. In contrast, the size of the N-glycan chain on the glucose transporter (GLUT1) from MkMk cells was smaller than that on GLUT1 from normal cells. The possible role of GPA in the biosynthesis and anion transport activity of band 3 in normal RBCs is discussed.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Abnormal immunological development in fetuses with trisomy 18.

Flow cytometry was used to enumerate the lymphocyte subpopulations in fetal blood obtained by cordocentesis from eight trisomy 18 fetuses at 20-36 weeks' gestation. Compared with values in chromosomally normal fetuses, in trisomy 18 the mean T- and natural killer (NK) cell counts were significantly lower (t = -7.63, P < 0.001 and t = -3.58, P < 0.01, respectively); the mean B-cell count was not significantly different (t = -1.32). These findings demonstrate that in trisomy 18 there is abnormal intrauterine development of the immune system.

B-Lymphocytes↗

Platelet size and glycoprotein Ib and IIIa expression in normal fetal and maternal blood.

OBJECTIVE: Our purpose was to study platelet size and surface glycoprotein expression in normal fetal and maternal blood throughout pregnancy. STUDY DESIGN: A cross-sectional study was performed at the Harris Birthright Research Centre for Fetal Medicine, King's College Hospital Medical School, London. Fetal and maternal blood samples were obtained from uncomplicated pregnancies at 8 to 42 weeks' gestation (n = 101 and n = 117, respectively) and from 30 nonpregnant controls. Flow cytometry was used to determine platelet size and glycoprotein Ib and IIIa expression both before and after stimulation with adenosine diphosphate. RESULTS: Mean platelet size in both fetal and maternal blood was significantly lower than that of nonpregnant controls and decreased with advancing gestation. The surface density of glycoprotein Ib in maternal and fetal platelets was significantly lower than in nonpregnant controls but did not change with gestation. Adenosine diphosphate stimulation of maternal platelets resulted in increased percentage expression and surface density of all glycoproteins, whereas stimulation of control platelets resulted in increased surface density of glycoprotein Ib and percentage expression of glycoprotein IIIa. Adenosine diphosphate stimulation of fetal platelets resulted in increased surface density of glycoprotein Ib and IIIa. CONCLUSION: Pregnancy is associated with increased thrombocytopoiesis in both the mother and fetus. Maternal platelet glycoprotein expression and responsiveness to adenosine diphosphate stimulation is increased. Fetal platelets are phenotypically mature from at least 12 weeks' gestation and respond in an adultlike fashion to stimulation with adenosine diphosphate.

Adenosine Diphosphate↗

Labor: an immunologically beneficial process for the neonate.

Leukocyte counts and lymphocyte subpopulations were measured in umbilical cord blood obtained from normal pregnancies delivered either vaginally or by elective cesarean section. In the group delivered vaginally there were significantly higher median values for neutrophils, monocytes, and natural killer cells. The leukocytosis associated with labor is selective for mediators of nonspecific or innate immunity. Labor may be an immunologically beneficial process for the neonate.

Antigens, CD↗

Predicting the severity of rhesus alloimmunization: monocyte-mediated chemiluminescence versus maternal anti-D antibody estimation.

Anti-D haemolytic antibody concentration and chemiluminescence (CLT) opsonic index was measured in maternal blood obtained from 20 alloimmunized pregnancies at 17-28 weeks undergoing intrauterine fetal blood sampling for the estimation of fetal haemoglobin concentration. The fetal haemoglobin concentration was significantly associated with the maternal serum CLT opsonic index (r = -0.566, P < 0.01) but not with the maternal anti-D concentration (r = -0.329). The data of this study indicate that measurement of maternal serum CLT opsonic index may be more accurate than anti-D quantification in providing non-invasive prediction of the degree of fetal anaemia.

Anemia↗

Subpopulations of CD34-positive haemopoietic progenitors in fetal blood.

Flow cytometry was used to determine the percentage and number of circulating CD34+ cells in fetal blood from 100 pregnancies at 13-38 weeks gestation. When expressed as a percentage of the total number of lymphocytes, the proportion of CD34+ cells decreased exponentially from a mean of 11.1% (9.2 x 10(7)/l) at 13 weeks to 1.0% (3.0 x 10(7)/l) at 38 weeks (r = 0.751, P < 0.0001). The use of primitive fetal blood CD34+ progenitor cells for prenatal somatic gene therapy may have distinct advantages over postnatal somatic gene therapy.

Antigens, CD↗

Fetal immunological and haematological changes in intrauterine infection.

OBJECTIVE: To study fetal immunological and haematological changes to intrauterine infection. DESIGN: In 37 pregnancies at risk of intrauterine infection, fetal blood obtained by cordocentesis at 20 to 36 weeks gestation was used for differential leucocyte counts, platelet count, enumeration of lymphocyte subpopulations, and neutrophil adhesion receptor expression. SETTING: Harris Birthright Research Centre for Fetal Medicine, London. RESULTS: All four fetuses with viral infections had platelet counts below the 5th centile and three had natural killer (NK) cell counts greater than the 95th centile of the normal range. Similarly, all five fetuses with bacterial or candidal infection had neutrophil counts greater than the 95th centile of the normal range; lymphocyte subpopulations were normal. CONCLUSIONS: In pregnancies complicated by intrauterine infection, fetuses exhibit NK cell lymphocytosis and thrombocytopenia in response to viraemia, and neutrophilia in response to bacteraemia from at least 21 weeks gestation.

Bacterial Infections↗

Fetal lymphocyte subpopulations in red blood cell iso-immunised pregnancies.

OBJECTIVE: To study the association between fetal anaemia and alterations in lymphocyte subpopulations. DESIGN: Cross-sectional study. SETTING: The Harris Birthright Research Centre for Fetal Medicine, King's College Hospital Medical School, London. SUBJECTS: Forty-three red blood cell iso-immunised pregnancies undergoing cordocentesis at 19 to 38 weeks gestation. MAIN OUTCOME MEASURES: Fetal blood haemoglobin concentration, erythroblast count and lymphocyte subpopulations. RESULTS: The mean T (CD3+), B (CD19+), T-helper (CD4+), T-suppressor/cytotoxic (CD8+) and natural killer (NK: CD16+/CD56+) cell counts in the anaemic fetuses were significantly lower than the appropriate normal mean for gestation (CD3+: t = -3.25, P < 0.01; CD19+: t = -2.14, P < 0.05; CD4+: t -4.03, P < 0.001; CD8+: t = -3.39, P < 0.01 and CD16+/CD56+: t = -3.49, P < 0.01). Furthermore, there was a significant association between the decrease in T lymphocyte number and the degree of fetal anaemia (r = 0.342, P < 0.05). CONCLUSIONS: Fetuses from red blood cell iso-immunised pregnancies exhibit nonselective lymphopenia that is proportional to the degree of anaemia.

Anemia↗

Umbilical cord blood erythroblast count as an index of intrauterine hypoxia.

The relation of umbilical cord blood arterial pH, Apgar score, leucocyte count, and erythroblast count at delivery with the diagnosis of fetal distress in labour was studied prospectively in three groups of singleton pregnancies delivering at term vaginally (55 infants), by elective caesarean section (39 infants), or by emergency caesarean section for abnormal intrapartum fetal heart rate patterns (55 infants). In the emergency caesarean section group the umbilical cord blood arterial pH was significantly lower and the leucocyte and erythroblast counts were higher than in the elective caesarean section group. Comparison of the emergency caesarean section and spontaneous vaginal delivery groups showed significant differences for pH and erythroblast count, but not for leucocyte count. In the spontaneous vaginal delivery group erythroblastosis was associated with umbilical cord blood pH, whereas leucocytosis was associated with the length of labour. The five minute Apgar score was > or = 7 in all infants. This study suggests that leucocytosis is a non-specific response of the fetus to labour, whereas erythroblastosis reflects fetal tissue hypoxia.

Erythroblasts↗

Management of the third stage of labour in women at low risk of postpartum haemorrhage.

OBJECTIVE: To compare active management with physiological management of the third stage of labour in women at low risk of postpartum haemorrhage. DESIGN: Randomised allocation of women in labour at low risk of postpartum haemorrhage to either physiological or active management of the third stage. SETTING: Labour ward in a district general hospital. PATIENTS: 193 Women with spontaneous vaginal delivery at term completed the study. Exclusion criteria were induction or augmentation of labour, antepartum or previous postpartum haemorrhage, premature rupture of membranes, previous caesarean section, raised blood pressure, cervical lacerations and third degree tears. INTERVENTIONS: Active management with syntometrine and controlled cord traction; or physiological management, where the cord was not clamped and the placenta was delivered by maternal effort. MEASUREMENTS: Blood loss was measured subjectively at delivery and estimated objectively by comparing the haemoglobin in labour with that on the third postpartum day. The duration of the third stage was also measured as was the incidence of retained placenta and blood transfusion. RESULTS: There was no significant difference in the estimated blood loss or haemoglobin drop between the two groups (P > 0.5). In addition the duration of the third stage was significantly longer in the physiological group (P < 0.001). Out of 90 women having physiological management, 7 received oxytocics for presumed postpartum haemorrhage. Only one case in the active group required further oxytocics and one other case in this group required a manual removal of placenta. CONCLUSIONS: This preliminary study confirms that active management results in a reduction in the length of the third stage of labour. However, it suggests that active management does not reduce blood loss when compared to physiological management in the woman at low risk of postpartum haemorrhage.

Delivery, Obstetric↗

Fetal plasma interferon gamma concentration in normal pregnancy.

OBJECTIVE: Our purpose was to investigate changes with gestation in fetal plasma interferon gamma concentration. STUDY DESIGN: A cross-sectional study at the Harris Birthright Research Centre for Fetal Medicine, London, was performed. Enzyme-linked immunoassay was used to measure plasma concentration in 54 fetal blood samples obtained by cordocentesis or cardiocentesis at 12 to 37 weeks' gestation. RESULTS: The concentration of interferon gamma in fetal plasma decreased exponentially from a mean of 1.2 U/ml at 12 weeks' gestation to a mean of 0.5 U/ml at 37 weeks (r = 0.460, p < 0.001). CONCLUSIONS: The presence of high levels of fetal interferon gamma in the first trimester suggests that it may play an important role in early fetal immunologic development. Furthermore, this study has established reference ranges for interferon gamma that may be of value in the prenatal diagnosis of congenital infection.

Cross-Sectional Studies↗

Abnormal fetal immunological development in Down's syndrome.

OBJECTIVE: To investigate the intrauterine development of the immune system in Down's syndrome. DESIGN: Cross sectional study. SETTING: Harris Birthright Research Centre for Fetal Medicine, London, UK. SUBJECTS: 16 fetuses with Down's syndrome and 104 fetuses with a normal karyotype at 17-24 weeks gestation. MAIN OUTCOME MEASURE: Flow cytometry was used to enumerate T (CD3+), B (CD19+) and NK (CD3- & CD16+/CD56+) lymphocyte subpopulations in fetal blood obtained by cordocentesis. RESULTS: The median numbers of T, B and NK lymphocytes in fetuses with Down's syndrome (1.52 x 10(9)/l, 0.08 x 10(9)/l, and 0.10 x 10(9)/l, respectively) were significantly lower than in the chromosomally normal fetuses (T lymphocytes: 1.98 x 10(9)/l, z = 3.04, P < 0.01; B lymphocytes: 0.50 x 10(9)/l, z = 5.84, P < 0.0001; and NK lymphocytes: 0.19 x 10(9)/l, z = 3.14, P < 0.01). CONCLUSION: These data demonstrate that in Down's syndrome, there is abnormal intra-uterine development of the immune system.

B-Lymphocytes↗

Fetal immunodeficiency: a consequence of placental insufficiency.

OBJECTIVE: To study the effect of placental insufficiency on fetal lymphocyte subpopulations. STUDY DESIGN: Cross sectional study of 19 growth retarded fetuses undergoing cordocentesis at 24 to 37 weeks gestation. Flow cytometry was used to enumerate fetal blood lymphocyte subpopulations. RESULTS: The mean T (CD3+), B (CD19+), T-helper (CD4+), T-suppressor/cytotoxic (CD8+) cell counts and the CD4 to CD8 ratio in the growth retarded fetuses were significantly lower than respective normal mean for gestation (CD3+: z = 3.66, P < 0.001; CD19+: z = 2.18, P < 0.05; CD4+: z = 3.76, P < 0.001; CD8+: z = 2.26, P < 0.05; and CD4/CD8: z = 2.27, P < 0.05). There were significant associations between the decrease in the T lymphocyte subpopulations and the degree of fetal acidaemia. CONCLUSIONS: Growth retarded fetuses demonstrate immune abnormalities that could be attributed to intrauterine starvation.

CD4-CD8 Ratio↗