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Biomedical subjects

S C Bell

Publications and source records attributed to S C Bell.

At least 55 records · Page 3Linked to original sources
PubMed2000

Metabolic and inflammatory responses to pulmonary exacerbation in adults with cystic fibrosis.

BACKGROUND: We hypothesized that increased resting energy expenditure in adults with cystic fibrosis was related to chronic inflammation secondary to pulmonary infection and could be modified by treatment of the underlying infection. METHOD: To determine the relationship between resting energy expenditure and the inflammatory and metabolic responses, we studied 22 adults with cystic fibrosis and chronic Pseudomonas aeruginosa infection before and after treatment of a respiratory exacerbation. Resting energy expenditure was measured by indirect calorimetry. Spirometry and circulating concentrations of C-reactive protein, neutrophil elastase alpha1-antiproteinase complex, catecholamines, non-esterified fatty acids and glycerol were determined. RESULTS: The mean (95% confidence interval)% predicted FEV1 was 28.5% (20.6, 36.4) and mean body weight 50.7 kg (47.4, 54.1). Following treatment, 1-s forced expiratory volume (FEV1) and weight increased, while C-reactive protein (P<0.0001) and neutrophil elastase alpha1-antiproteinase complex concentrations (P<0.0001) were reduced. Resting energy expenditure decreased from 6.8 (6.3, 7.2) to 6.25 (5.9, 6.6) MJ day-1 by day 15 (P<0.001). Changes in resting energy expenditure and C-reactive protein were related (r = 0.66, P< 0.0001). Weight gain was inversely related to resting energy expenditure (r = 0.43, P = 0.02) and unrelated to energy intake (r = 0.02, P = 0.47). Post-treatment reduction in norepinephrine was related to changes in heart rate (r = 0.57, P<0.01), resting energy expenditure (r = 0.51, P = 0.001) and non-esterified fatty acids (r = 0.42, P< 0.05). CONCLUSIONS: A parallel reduction in the host inflammatory and catabolic responses followed treatment of a respiratory exacerbation and may have contributed to weight gain.

Adult↗
PubMed2000

Myofibroblast differentiation in the connective tissues of the amnion and chorion of term human fetal membranes-implications for fetal membrane rupture and labour.

An area of the fetal membranes, within the rupture tear after spontaneous delivery at term, exhibits altered morphology compared to more distal sites. It is characterized by marked swelling of the amniotic and chorionic connective tissue layers, consistent with structural weakness, and a marked reduction of the thickness of both the cytotrophoblast and decidual layers. These features, albeit less extreme, have been identified in fetal membranes in the lower uterine pole in patients prior to labour. In this study of pre-labour, labour-affected and post-labour term fetal membranes, we report that these regions are associated with an alteration in the phenotype of the vimentin positive mesenchymal cell population of the chorionic connective tissue reticular layer, and are consistent with myofibroblastic differentiation, i.e. alpha-smooth muscle actin (alpha-sma) expression. In the reticular layer of the lower uterine pole biopsies in the labour-affected group the numbers and densities of alpha-sma immunoreactive positive cells were 17-fold (P=0.04) and 8.5-fold (P=0.02) higher than in mid-zone biopsies. After delivery, in rupture line biopsies the numbers and densities were 50-fold (P=0. 002) and 36-fold (P=0.003) higher compared to mid zone biopsies. The percentage of the vimentin positive population positive for alpha-sma was 2-5 per cent in mid-zone biopsies compared to 49 per cent (P=0.03) in the labour-affected 'cervical' biopsies and 69 per cent (P=0.05) in the rupture line biopsies. Within the tear sites, alpha-sma positive cells were also detected within the fibroblastic layer of the amniotic connective tissue. Although there was no significant difference between the numbers and density of alpha-sma cells in the reticular layers between mid and lower uterine pole biopsies in the pre-labour group, in a proportion of patients the biopsies were similar to labour-affected biopsies indicating that this alteration occurs prior to clinically apparent labour in these patients. The incidence of alpha-sma positive cells in the reticular layer correlated with morphological changes within the fetal membranes, for example thickness of reticular (r(2)=0.349, P=0.0006) and amniotic connective tissue layers (r(2)=0.389, P=0.0002). This suggests that cellular activities associated with myofibroblastic differentiation in the reticular layer of the chorion may be associated with the observed connective tissue changes, fetal membrane rupture and labour.

Actins↗
PubMed2000

The effect of hormone replacement therapy on the immunoreactive concentrations in the endometrium of oestrogen and progesterone receptor, heat shock protein 27, and human beta-lactoglobulin.

We determined the expression of oestrogen receptor (ER), progesterone receptor (PR), heat shock protein 27 (HSP27) and human beta-lactoglobulin in the endometrium under hormone replacement therapy (HRT). The immunohistochemical expression during the late progestogenic phase of sequential HRT was compared semi-quantitatively and using image analysis, to the early, mid-, and late luteal phase of the physiological cycle. Under sequential HRT, smaller glands were positive for the ER but larger glands with more advanced secretory features were negative. ER expression was lower in the stroma under HRT, and the difference was statistically significant compared with the early luteal phase (P < 0.05). Expression of HSP27 under HRT was lower in the epithelium but higher in the stroma compared with the physiological luteal phase. Epithelial PR expression was lower under HRT compared with the early, but not the mid- or the late luteal phase. The number of PR-positive stromal cells under HRT was lower compared with the physiological cycle, and the difference was statistically significant in comparison with the early luteal phase (P < 0.05). The glandular area expressing human beta-lactoglobulin during the late progestogenic phase was statistically significantly higher compared with the early, but lower in comparison with the mid- or the late luteal phase (P < 0.05). The study demonstrates a sub-physiological progestogenic response superimposed on evidence of a hypo-oestrogenism, and a differential response in the epithelium and stroma.

Endometrium↗
PubMed2000

Prostaglandin E(2)-dependent production of latent matrix metalloproteinase-9 in cultures of human fetal membranes.

Studies in our laboratory have shown that structural changes in cervical biopsied fetal membranes, prior to labour, coincide with differences in the expression of the gelatinase enzyme, latent matrix metalloproteinase-9 (MMP-9). Concurrently, in vivo, there is an increase in the expression of prostaglandins, notably prostaglandin E(2) (PGE(2)), which has been shown to regulate the expression of MMPs in other systems. The aim of this study was to test the hypothesis (using an in-vitro culture model) that endogenously produced PGE(2) has a role in the elevation of MMP-9 described in vivo. Non-infected fetal membranes sampled from women undergoing elective Caesarean section were stimulated with 10% (v/v) fetal bovine serum (FBS), a known inducer of prostaglandins. This activation resulted in a time-dependent increase in the secretion of PGE(2) into the media, as determined by enzyme-linked immunosorbent assay (day 1: 19 +/- 9 pg/ml/24 h to 358 +/- 54 pg/ml/24 h by day 4). A similar pattern of secretion of latent MMP-9 was observed in parallel with the increase in PGE(2) in the same culture media (day 1: 1.63 +/- 0.17 ng/ml/24 h to 4.2 +/- 1.4 ng/ml/24 h by day 4). When both molecules were compared, a significant (P: < 0.01) positive correlation (r = 0.623) was observed. Secretion of the tissue inhibitor of MMPs-9 (TIMP-1) was not significantly different between untreated (3.07 +/- 0.266 microg/ml/24 h) and FBS-treated (3. 85 +/- 0.24 microg/ml/24 h) cultures during the first 4 days in culture. Prostaglandin synthesis inhibition studies using indomethacin (100 micromol/l) resulted in a 70-80% reduction in the activated secretion of latent MMP-9. Direct PGE(2) stimulation of cultures resulted in the bell shaped dose-response curve with concentrations of 1-100 nmol/l (which are within the range secreted in culture in response to FBS), stimulating significant latent MMP-9 secretion. These results suggest a link between endogenous PGE(2) and latent MMP-9 production in human fetal membranes, raising the possibility that PGE(2) has a role in the mechanism of fetal membrane structural changes and, hence, in parturition-associated membrane rupture.

Cell Survival↗
PubMed2000

Reactive thrombocytosis after caesarean section and vaginal delivery: implications for maternal thromboembolism and its prevention.

OBJECTIVE: To assess the duration and severity of reactive thrombocytosis after caesarean section and vaginal delivery. DESIGN: A prospective cohort study. SETTING: A large teaching hospital. METHODS: Women admitted for delivery at the Leicester Royal Infirmary were recruited into the study. The platelet count was measured before delivery and postnatally on days 3, 8, 12, 16, 20 and 24. Women who had antepartum haemorrhage, postpartum haemorrhage and those delivered by instrumental delivery were excluded from the study. Sixty-five were recruited, and 45 completed the study, 20 of whom were delivered by a normal vaginal delivery and 25 by caesarean section. A random effects model was used to compare platelet counts within and between the two groups to assess the severity and the timing of reactive thrombocytosis. RESULTS: There were no statistically significant differences in booking and pre-delivery platelet counts between the two groups (mean values 248.4 x 10(9)/L and 245 x 10(9)/L in the normal vaginal group and 269.4 x 10(9)/L and 251.6 x 10(9)/L in the caesarean section group, respectively). Postnatally, a rise in the platelet count was noted in the normal vaginal delivery group, reaching statistically significant peak values, compared with booking and pre-delivery at days 8 and 12 of the postnatal period (mean value 365.8 x 10(9)/L; P < 0.001 and 369.4 x 10(9)/L; P < 0.001 respectively). In the caesarean section group, the platelet count was raised to a statistically significant high value, compared with booking and pre-delivery at day 8 of the postnatal period. The platelet count peaked at days 12 and 16 of the postnatal period (mean value 522.5 x 10(9)/L; P < 0.0001 and 526.5 x 10(9)/L; P < 0.0001, respectively) and remained significantly higher than booking and predelivery values for 24 days after the caesarean section. There was a greater rise in the platelet count in the caesarean section group compared with the vaginal delivery group. The platelet counts in the caesarean section group were significantly higher than these in the normal vaginal delivery group from day 12 to day 24 of the postnatal period. CONCLUSION: A significant rise in platelet count occurred eight to twelve days after normal vaginal delivery and caesarean section. The increase in platelet count continued to rise for 16 days after caesarean section, and it stayed significantly higher for more than 24 days after the delivery.

Cesarean Section↗
PubMed2000

Microvascular complications in cystic fibrosis-related diabetes mellitus: a case report.

CONTEXT, The prevalence of cystic fibrosis-related diabetes mellitus is increasing and is associated with increased survival from cystic fibrosis. CASE REPORT, This study describes a case of the premature onset of disabling and widespread microvascular complications resulting from cystic fibrosis-related diabetes mellitus. Previously asymptomatic retinopathy was diagnosed on recognition of diabetic nephropathy. CONCLUSIONS, The treatment of pulmonary exacerbations has become more complex due to the nephrotoxic potential of intravenous aminoglycoside drugs which are frequently used to control chronic Pseudomonas infection in cystic fibrosis.

Adult↗
PubMed1999

Identification of a cycle-modulated 200-kDa endometrial antigen by a monoclonal antibody LDS60.

We have developed a mouse monoclonal antibody, LDS60, against a cycle-dependent antigen by immunising (MF1 x BALB/c)F1 mice with a human endometrial membrane preparation. In formalin fixed paraffin embedded sections, LDS60 identified an epithelial specific antigen which exhibited a specific pattern of expression during the menstrual cycle. It was only occasionally expressed during the proliferative phase. During the early-secretory phase, there was intracytoplasmic staining in about half of the glands examined. This was in the form of small microvesicles, either near the base of the cell or supranuclear. In the mid-secretory phase the same proportion of glands exhibited staining in the form of micro-vesicles that were noted to accumulate nearer to the cell apices. In the late-secretory phase, there was no intracytoplasmic staining and the antigen was localised to the luminal border of the glandular epithelium and some staining appeared within the gland lumen of approximately 20% of glands. It is also diffusely expressed in some mucous secreting cells in the tongue, stomach and colon, as well as lung pneumocytes. The antigen has a molecular weight of approximately 200 kDa as identified by immunoblotting. This antigen exhibits similarities to MUC-1 which is involved in uterine receptivity and could therefore have a similar role. Its cycle modulation suggests that it could be used to monitor the uterine response to steroids.

Animals↗
PubMed1999

Repeatability and methodology of resting energy expenditure in patients with cystic fibrosis.

In this study, intra-individual variation of resting energy expenditure (REE) in adults with cystic fibrosis (CF) and the effect of measurement duration were determined. Twelve adults with CF and chronic Pseudomonas aeruginosa (Ps. aeruginosa) infection and 12 healthy volunteers, matched for age and sex were studied whilst clinically stable on days 1.2, and 15. Respiratory gas exchange was monitored by continuous measurement of oxygen uptake (VO2) and carbon dioxide production (VCO2) using a ventilated hood indirect calorimeter. Coefficients of variation (CVs) were 4.3% in patients and 2.4% in controls comparing days 1 and 2. The CV for patients was 5.0% and for controls 2.9% comparing days 1 and 15. The effect of measurement duration on REE was assessed in eight of the CF patients. REE remained stable for 40 min but tended to rise by 80 min. Plasma catecholamine concentrations were stable between study days in patients but fell with time in controls suggesting some adaptation to experimental procedure. The greater variability of REE in patients was related to change in serum CRP over 2 weeks. REE is a repeatable measurement in clinically stable patients with CF, though variability was greater in patients than healthy subjects. This has implications for the design and interpretation of longitudinal studies of REE in patients with chronic lung disease.

Adrenal Cortex Hormones↗
PubMed1999

Expression of mRNA encoding insulin-like growth factors I and II by uterine tissues and placenta during pregnancy in the rat.

The uterus and the placenta synthesize insulin-like growth factors (IGFs) and insulin-like binding proteins (IGFBPs). These growth factors are implicated in processes of proliferation and differentiation that occur in the uterus. To determine the patterns of expression of IGFs during rat pregnancy we used in situ hybridization with digoxigenin labeled probes on uterus from day 7 to day 16 of pregnancy. In early gestation days (7-8) both IGF mRNAs showed similar tissue distribution with relative abundance in the stroma and circular muscle layer. On days 11 and 12 expression for IGF-I mRNA was found in the mesometrial decidua and metrial gland and in the ectoplacental cone while clear expression of IGF-II mRNA could only be found in the latter. On days 13 and 14, expression for IGF-I mRNA could be detected in the mesometrial decidua and metrial gland but no expression was observed for IGF-II mRNA. A gradient of IGF-I mRNA expression could be observed in the placenta on day 16, with the trophoblastic cells of the basal zone expressing the signal with stronger intensity than in the labyrinthine zone. For IGF-II mRNA the highest expression was associated with the labyrinthine zone. Endovascular trophoblast was positive for both mRNAs. The spatial and temporal patterns of expression suggests a role for IGFs in the process of decidualization as well as in the establishment, growth and differentiation of the various trophoblast cells of the placenta.

Animals↗
PubMed1999

Structural characteristics of term human fetal membranes prior to labour: identification of an area of altered morphology overlying the cervix.

Premature rupture of fetal membranes can have serious clinical implications, especially for the initiation of preterm labour and its consequences. To account for this phenomenon many studies have attempted to identify membrane features that may be uniquely associated with the site of rupture. Our previous work has identified an area of the fetal membrane, following spontaneous term birth which exhibits alterations consistent with structural weakness. The aim of this study was to determine if these changes existed prior to labour. In formalin-fixed paraffin-embedded tissue sections an area of the fetal membrane overlying the cervix, termed the 'cervical membranes', was characterized by an increased thickness of the connective tissue layer (215% increase, P < 0.01) and decreased thickness of both the cytotrophoblast (36% reduction, P < 0.01) and decidual layers (64% reduction, P < 0.01) compared to the rest of the membrane. This resulted in the cervical membranes being significantly thinner (P < 0.05) than the rest of the membrane. Similar changes were also detected in frozen sections of fetal membranes. These regional differences have two important implications in that: (i) the cervical membrane may represent a region of structural weakness susceptible to rupture during labour, and (ii) the paracrine relationships between fetal membranes and the myometrium may be qualitatively affected within different regions of the uterus.

Amnion↗
PubMed1999

Increased incidence of apoptosis in non-labour-affected cytotrophoblast cells in term fetal membranes overlying the cervix.

A regional reduction in the cellularity of the cytotrophoblastic and decidual layers occurs in the fetal membranes overlying the cervix in the lower uterine segment prior to labour. Although the mechanism(s) involved are not known it could result from regionally increased apoptosis, the histological manifestation of programmed cell death, or decreased proliferation. Apoptosis was assessed in regionally sampled fetal membranes from women undergoing elective Caesarean section (n = 14) by the presence of apoptotic bodies by light and electron microscopy. Cell proliferation was assessed by immunocytochemical detection of the protein Ki-67. Apoptotic bodies were identified in all regions of the fetal membrane with the highest incidence found within the cytotrophoblast layer. However, this layer in fetal membranes biopsied over the cervix contained significantly more apoptotic bodies (mean +/- SD 0.085 +/- 0.020%) compared to the layer in fetal membranes obtained from the mid-zone (0.020 +/- 0.008%) apoptotic bodies. Isolated Ki-67 positive cells were detected in the cytotrophoblast layer, but no regional differences in their incidence were seen. Fetal membranes also failed to exhibit significant immunoreactivity for BCL-2 but exhibited strong BAX immunoreactivity within the decidual layer. We conclude that the regionally increased incidence of apoptosis in the cytotrophoblastic layer in the membrane overlying the cervix may account for the reduction in its cellularity but not the relative decrease in the decidual layer. Given the consequence of the loss of local function in degrading uterotonins and stabilizing the fetal membrane, the study of the regulation of apoptosis in these cells may have important implications for fetal membrane rupture and parturition.

Amnion↗
PubMed1999

The effect of hormone replacement therapy on the number and the proliferation index of endometrial leukocytes.

This study aimed to determine the changes in endometrial leukocyte subpopulations under sequential hormone replacement therapy (HRT) during the late progestogenic phase. The number of leukocytes was determined using immunohistochemistry utilizing monoclonal antibodies to CD45 (total leukocytes), CD56 (endometrial granulated lymphocytes), CD3 (T-cells), and CD68 (macrophages). Leukocyte proliferation was demonstrated using in-situ hybridization with a histone probe, and the proliferation index was determined using double labelling for Ki67 (Mib1). Compared to the corresponding phase of the physiological cycle, sequential HRT-treated endometrium exhibited a 95% increase in CD45(+) cells (P < 0.05), a 130% increase in CD56(+) cells (P < 0.05), and a 113% increase in CD3 cells. There was a non-statistically significant drop in the number of CD68(+) cells. The number of proliferating leukocytes increased in sequential HRT endometrium.

Antibodies, Monoclonal↗
PubMed1999

Alternatively spliced tenascin-C mRNA isoforms in human fetal membranes.

Tenascin-C is an extracellular matrix glycoprotein whose monomers include eight consecutive fibronectin type III-like repeats, encoded by exons 10-16, and which are subject to alternative splicing. Transcripts containing these exons are expressed during tissue wounding and active tissue remodelling. Human fetal membranes have been proposed to undergo active tissue remodelling as part of the mechanisms leading to their rupture and immunoreactive tenascin-C has been detected in this tissue. Employing reverse transcription-polymerase chain reaction (RT-PCR) and exon-specific primers, products corresponding to multiple splicing events in the alternatively spliced region have now been identified. The overall splicing pattern would indicate that the major transcripts correspond to complete exclusion of the alternatively spliced region; inclusion of only exon 16; and inclusion of exons 10-14 and 16, including or excluding exon 12. The sole site in tenascin-C susceptible to cleavage by matrix metalloproteinases (MMP)-2 and MMP-3 is found within the exon 12 encoded repeat, therefore translation of isoforms which include or exclude exon 12 may produce 'large' tenascins mediating functions ascribed to this form but susceptible or resistant to these MMPs. The demonstration of expression of 'large' tenascin mRNA isoforms supports the concept that fetal membranes at term are a site of active tissue remodelling.

Alternative Splicing↗
PubMed1999

Localization of ubiquitin and ubiquitin cross-reactive protein in human and baboon endometrium and decidua during the menstrual cycle and early pregnancy.

We have examined the distribution of ubiquitin and the related ubiquitin cross-reactive protein (UCRP) in paraffin-embedded sections of human and baboon endometrium and decidua by immunoperoxidase or immunofluorescence cytochemistry with antibodies raised against ubiquitin, UCRP, CD45, and insulin-like growth factor-binding protein-1. Anti-ubiquitin immunoreactivity was present in the nonpregnant endometrium, particularly in the glandular epithelial cells, and up-regulated in endometrial stromal cells as they decidualized at the beginning of pregnancy. Anti-UCRP immunoreactivity was absent from nonpregnant tissue but accumulated to high levels in decidual cells during pregnancy. Western blotting indicated that immunoreactivity was primarily due to the presence of ubiquitin and UCRP conjugated to other proteins, and that although levels of ubiquitin-protein conjugates do not change substantially during pregnancy, decidualization is accompanied by the appearance of conjugates of UCRP. Baboon uterine tissues demonstrated a similar distribution of the two proteins, which indicates that the baboon may be a useful model for study of the role of the ubiquitin system and UCRP in the establishment of pregnancy in humans.

Animals↗
PubMed1999

The role of observer error in antenatal dipstick proteinuria analysis.

OBJECTIVE: To determine the role of inter-observer error and the influence of training upon dipstick urine analysis. DESIGN: A two phase observational and training study. METHODS: Five standard solutions of serum albumin were used to test the accuracy of midwives and nursing auxiliaries involved in dipstick urine analysis at a maternity hospital. The standard solutions were chosen such that they should have resulted in negative (n = 2) and positive (n = 3) dipstick test results, respectively. SETTING: A teaching maternity hospital and academic department of obstetrics and gynaecology. PARTICIPANTS: Twenty midwives, 20 nursing auxiliaries and nine laboratory technicians. RESULTS: For the two nonproteinuric solutions, a higher false positive rate was observed for nursing auxiliaries (40% and 55%), compared with midwives (5% and 30%) (P = 0.020 and P = 0.20, respectively). Before training, laboratory technicians recorded high false positive rates (67% and 89%), but after training these were reduced to 0% and 22% (P = 0.25 and P = 0.023, respectively). Both nursing auxiliaries and midwives recorded false negative rates of between 10% and 45% for the three proteinuric solutions. CONCLUSIONS: Observer error may be reduced by assigning midwives to urine dipstick analysis or by the implementation of directed training. Classification of pre-eclampsia or other hypertensive diseases of pregnancy on the basis of the presence and degree of proteinuria should be confirmed with a 24-hour quantitative protein collection.

False Negative Reactions↗