Biomedical subjects

F Boswell

Publications and source records attributed to F Boswell.

15 recordsLinked to original sources

PubMed1999

Expression of intercellular adhesion molecules ICAM-1 and ICAM-2 in human endometrium: regulation by interferon-gamma.

The purpose of this study was to localize intercellular adhesion molecule (ICAM)-1 and ICAM-2 in human endometrium and myometrium throughout the menstrual cycle, and to determine whether the expression of these molecules is regulated by interferon (IFN)-gamma. ICAM-1 and ICAM-2 distribution was examined in endometrial biopsies by immunocytochemistry, and Northern blotting was used to quantify ICAM-1 and ICAM-2 mRNA expression in isolated endometrial glands. Stromal fibroblast cultures were exposed to IFN-gamma and the effect on expression of ICAM-1 and ICAM-2 was determined by immunocytochemistry and Northern blotting. ICAM-1 was localized in vivo to the apical surface of the glandular epithelium, the vascular endothelium and endometrial stromal cells throughout the menstrual cycle. Stromal expression of ICAM-1 was up-regulated in menstrual specimens. Northern blotting confirmed the presence of ICAM-1 mRNA in isolated endometrial glands. The expression of ICAM-1 antigen and message was increased in stromal cell culture after incubation with IFN-gamma in a time-dependent manner, suggesting that this cytokine stimulates the expression of ICAM-1 in the endometrial stroma. ICAM-2 antigen expression was restricted to the vascular endothelium. ICAM-2 mRNA was absent in endometrial glands. The widespread distribution of ICAM-1 in human endometrium suggests that this molecule is involved in the process of menstruation, the functioning of glands, blood vessels and stroma, and in regulating leukocyte trafficking into the tissue. ICAM-2 is restricted to the vascular endothelium where it might modulate leukocyte invasion of the stroma and myometrial connective tissue.

Antigens, CD↗

PubMed1998

The neutrophil and preeclampsia.

Endothelial injury is common to all pathological features of preeclampsia. Neutrophil activation has been implicated in the pathophysiology of preeclampsia and requires binding and transmigration of neutrophils through the endothelium. This occurs via an interaction of endothelial adhesion molecules and surface receptors on neutrophils. Upon activation, neutrophil granules are released, the contents of which are capable of mediating vascular damage. In addition, leukotrienes are synthesized, and superoxide is generated in a respiratory burst. These products also provoke vascular damage. Neutrophil recruitment to the endothelium involves express of P-selectin and released of platelet activating factor from the endothelium. In preeclampsia there is evidence of an increase in neutrophil activation with up-regulation of neutrophil integrin expression and increased regulation of the protease elastase. Furthermore, these markers of neutrophil activation correlate with established markers of disease severity. The primary mechanism of neutrophil activation is unknown, but neutrophils in preeclampsia appear to have normal motor activity. Several potential mechanisms of neutrophil activation have been identified. They include up-regulation of cellular adhesion molecules on the endothelial surface, increased generation of tumor necrosis factor-alpha, and endothelial activation from hyperlipidemia. In additional to activation of neutrophils in preeclampsia, there may be involvement of the interleukin-6 and endothelin-1 in "priming" neutrophils for subsequent superoxide production. Activated neutrophils are likely to play a large part in the arteriopathy and endothelial damage associated with preeclampsia, but it is unclear whether neutrophil activation is the cause or the consequence of endothelial damage.

Biomarkers↗

PubMed1997

Circulating cell adhesion molecule concentrations in diabetic women during pregnancy.

OBJECTIVE: To determine whether circulating concentrations of defined cell adhesion molecules, which are thought to reflect endothelial expression, are increased in insulin-dependent diabetic women during pregnancy. METHODS: Pregnant diabetic women demonstrating good glycemic control and without major complications before pregnancy were studied at 8-12 (n = 15), 18 (n = 15), 28 (n = 16), 32 (n = 16), and 36 (n = 16) weeks' gestation. A subgroup of ten diabetic women was sampled longitudinally through all five gestational ages. The diabetic women were compared with healthy nondiabetic women sampled cross sectionally at 12 (n = 20), 28 (n = 19), and 36 (n = 19) weeks' gestation. Nonpregnant diabetic (n = 22) and nonpregnant nondiabetic women (n = 28) also were studied. Plasma concentrations of the cell adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular endothelial cell adhesion molecule-1 (VCAM-1) were measured by enzyme-linked immunosorbent assay. RESULTS: Significantly higher median (range) concentrations of E-selectin (63.0 [20.2-107.0] ng/mL) and ICAM-1 (281.5 [171.6-778.4] ng/mL) but not VCAM-1 (459.7 [301.0-909.7] ng/mL) were found in nonpregnant diabetic women compared with nonpregnant nondiabetic women (43.5 [18.1-93.2], 243.6 [174.4-329.2], and 476.0 [253.8-929.4] ng/mL, respectively). During pregnancy these significant differences between diabetic and control groups were lost. The median (range) concentration of E-selectin (50.0 [21.2-96.3] ng/mL) was significantly lower in pregnant compared with nonpregnant diabetic women. The plasma concentrations of E-selectin and ICAM-1 did not change significantly with gestation in either diabetic or nondiabetic pregnant groups. Vascular endothelial cell adhesion molecule-1 concentration changed significantly with gestation in the diabetic pregnant group only. CONCLUSION: Circulating concentrations of defined vascular cell adhesion molecules are not increased abnormally in diabetic women with good glycemic control during otherwise uncomplicated pregnancy.

Adult↗

PubMed1997

Placental expression of vascular endothelial growth factor in placentae from pregnancies complicated by pre-eclampsia and intrauterine growth restriction does not support placental hypoxia at delivery.

In view of the pathological placental features of pre-eclampsia and intrauterine growth restriction (IUGR), and the angiogenic effects of vascular endothelial growth factor (VEGF), the aim of this study was to determine the expression of VEGF in placentae from normal pregnancies and to compare the results with placentae from pregnancies complicated by pre-eclampsia and intrauterine growth restriction (IUGR). ELISA was used to measure circulating VEGF immunoreactivity in umbilical vein serum samples and immunohistochemistry was used to determine tissue expression of the protein. Since VEGF is known to be upregulated by hypoxia, the expression pattern of VEGF would provide further clues to the oxygen status in the placentae at the time of sampling, presently a subject under great debate. The geometric mean concentration of VEGF immunoreactivity in umbilical vein serum of normal pregnant women was 112.46 pg/ml, in women with pre-eclampsia 50.23 pg/ml and in IUGR alone 175.35 pg/ml. These values were not statistically different from each other. Immunolocalization of VEGF in normal term villous placenta was observed in the syncytiotrophoblast with less intense staining in stromal cells. No qualitative differences in localization of staining between the groups (normal pregnancies, pre-eclampsia, pre-eclampsia plus IUGR, and IUGR) was found. Intensity of staining in stromal cells was also similar in the groups studied. However, intensity of VEGF immunostaining in syncytiotrophoblast was significantly reduced in the three pathological groups (P < 0.02) compared with the control group. These results suggest that reduced VEGF may be responsible, at least in part, for the impaired vascular development which occurs in these conditions. Our results are therefore not consistent with villous placental hypoxia at the time of sample collection.

Adult↗

PubMed1997

The activity of the methylpiperazinyl fluoroquinolone CG 5501: a comparison with other fluoroquinolones.

The in-vitro activity of CG 5501 against a wide range of recent clinical isolates was compared with that of three fluoroquinolones. CG 5501 inhibited 90% of the species of the family Enterobacteriaceae at 0.5 mg/L or less, exceptions being Enterobacter spp. (MIC90 2 mg/L) and Serratia spp. (MIC90 4 mg/L). Ninety per cent of Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter spp. were inhibited by 16, 4 and 1 mg/L respectively. CG 5501 had high activity against Gram-positive cocci, 90% of staphylococci being inhibited at 2 mg/L. Methicillin-resistant Staphylococcus aureus strains were generally ciprofloxacin-resistant yet were all susceptible to 4 mg/L or less of CG 5501. Isolates of Streptococcus pneumoniae were eight-fold more susceptible to CG 5501 (MIC90 0.5 mg/L) than to ciprofloxacin (MIC90 4 mg/L) and the former had a similar activity to that of trovafloxacin and sparfloxacin. Enterococcus faecalis was generally two- to four-fold more susceptible to CG 5501 or trovafloxacin than to ciprofloxacin. CG 5501 and trovafloxacin had high activity against Bacteroides fragilis (MIC90 0.25 mg/L). Five strains of Chlamydia spp. were inhibited by < or =0.12 mg/L of CG 5501; sensitive and multiresistant strains of Mycobacterium tuberculosis were inhibited by < or =0.5 mg/L of CG 5501. The high activity and breadth of its antibacterial spectrum suggests that CG 5501 should be useful in a wide range of clinical infections.

Anti-Bacterial Agents↗

PubMed1997

Suppression of serum vascular endothelial growth factor immunoreactivity in normal pregnancy and in pre-eclampsia.

OBJECTIVE: To determine whether vascular endothelial growth factor (VEGF) concentrations are altered in pre-eclampsia. DESIGN: Serum was prepared from peripheral venous blood and stored at -70 degrees C. Serum VEGF concentrations were measured by ELISA. SETTING: University of Glasgow Department of Obstetrics and Gynaecology, Royal Infirmary, Glasgow. PARTICIPANTS: Twenty-two healthy nonpregnant volunteer women, 34 normal pregnant women and 34 women with pre-eclampsia were studied. RESULTS: Serum concentrations of VEGF were significantly lower in normal pregnant women (median value 12.89 pg/mL) than in nonpregnant women (median value 166 pg/mL; P < 0.0001). In pre-eclampsia VEGF concentrations were significantly lower (median value 2.34 pg/mL) than normal pregnancies (P < 0.0001). Postpartum concentrations of VEGF in the group complicated by pre-eclampsia (median value 76.42 pg/mL) were not significantly different from nonpregnant values (P = 0.2). CONCLUSIONS: Our results show that serum concentrations of VEGF are suppressed in pregnancy and further reduced in pre-eclampsia. Further studies to elucidate the mechanisms which lead to a reduction in VEGF concentrations may provide new clues to the aetiology of this disorder.

Adult↗

PubMed1995

Expression of cell adhesion molecules in placentae from pregnancies complicated by pre-eclampsia and intrauterine growth retardation.

Platelets and neutrophils are involved in maternal placental vascular damage in pre-eclampsia. Recruitment of these cells is probably mediated by cell adhesion molecules expressed at the uteroplacental bed. It remains controversial as to whether platelets and neutrophils mediate damage to trophoblast or villous vasculature. The purpose of this study was to determine the expression of cell adhesion molecules in placentae from normal pregnancies and pregnancies complicated by pre-eclampsia and intrauterine growth retardation (IUGR). Immunostaining for platelet endothelial cell adhesion molecule (PECAM) and intercellular adhesion molecule-1 (ICAM-1) was localized mainly to the endothelium of stem villi, intermediate villi, terminal villi and decidual vessels. Scattered staining for ICAM-1 was also evident in the stroma and fetal membranes. The endothelium of stem villi, intermediate villi and terminal villi were all negative for vascular cell adhesion molecule-1 (VCAM-1) and E-Selectin. PECAM, ICAM-1 and ICAM-2 mRNA were all detectable in normal placentae using northern blotting analysis whereas mRNA for E-Selectin and VCAM-1 were both undetectable. There were no differences in cell adhesion molecule immunostaining or mRNA expression in placentae from pregnancies complicated by pre-eclampsia and IUGR inconclusion, expression of cell adhesion molecules in placentae from pre-eclampsia and IUGR are consistent with a normal physiological role in vascular function.

Antigens, CD↗

PubMed1995

The in-vitro activity of CP 99,219, a new naphthyridone antimicrobial agent: a comparison with fluoroquinolone agents.

The in-vitro activity of a new fluoroquinolone, CP 99,219 was compared with that of ciprofloxacin, DU 6859, sparfloxacin and levofloxacin. CP 99,219 showed generally similar in-vitro activity to the other compounds tested against the Enterobacteriaceae (MIC90 of all agents < 0.5 mg/L except Morganella morganii). It was found to be more active than ciprofloxacin, sparfloxacin and levofloxacin against the strains of Acinetobacter calcoaceticus tested (MIC90 1 mg/L). CP 99,219 was found to be four-fold more active against strains of Stenotrophomonas maltophilia than ciprofloxacin (MIC90 1 and 8 mg/L, respectively). Haemophilus influenzae and Neisseria spp. were highly susceptible to all the agents tested. CP 99,219 was more active than ciprofloxacin, sparfloxacin and levofloxacin against Gram-positive organisms, but less active than DU 6859. The enhanced anti-Gram-positive activity of CP 99,219 was most marked against the nine strains of methicillin-resistant Staphylococcus aureus tested. The MIC90 of CP 99,219 of these strains was 1.0 mg/L compared with 64 mg/L for ciprofloxacin. Against Bacteroides fragilis, CP 99,219 (MIC90 0.25 mg/L) and DU 6859 (MIC90 0.03 mg/L) were more active than the other quinolones. Chlamydia spp. were susceptible to < or = 0.12 mg/L of CP 99,219. Mycobacterial strains tested were less susceptible to CP 99,219 than to ciprofloxacin. The protein binding of CP 99,219 was 87.9% at 1 mg/L.

4-Quinolones↗

PubMed1994

The cell adhesion molecule, VCAM-1, is selectively elevated in serum in pre-eclampsia: does this indicate the mechanism of leucocyte activation?

OBJECTIVE: To determine whether circulating levels of cell adhesion molecules, markers of endothelial damage and leucocyte activation, were increased in pre-eclampsia. DESIGN: Serum was prepared from peripheral venous blood and stored at -70 degrees C. The cell adhesion molecules, VCAM-1, E-Selectin and ICAM-1, were measured by ELISA. SETTING: Department of Obstetrics and Gynaecology, Royal Infirmary, Glasgow. SUBJECTS: Sixteen primigravid women with pre-eclampsia were recruited for the study. The preeclampsia group were compared with 18 healthy primigravid women with uncomplicated pregnancies. RESULTS: The pre-eclamptic group had significantly higher serum levels of the cell adhesion molecule VCAM-1 (t = 3.673; P < 0.001). There were no significant differences in the adhesion molecules ICAM-1 or E-Selectin. CONCLUSIONS: Endothelial damage and dysfunction are common to all the pathological features of pre-eclampsia. This study shows that concentrations of cell adhesion molecules, which indicate leucocyte-endothelial attachment and activation, are elevated in the serum of patients with pre-eclampsia. Such increases in soluble circulating cell adhesion molecules may reflect increased expression of these molecules on the endothelium and thereby explain the mechanism for leucocyte activation in pre-eclampsia.

Adult↗

PubMed1994

Increased concentrations of cytokines interleukin-6 and interleukin-1 receptor antagonist in plasma of women with preeclampsia: a mechanism for endothelial dysfunction?

OBJECTIVE: To determine if plasma concentrations of defined cytokines are increased in women with preeclampsia, and to correlate any increases with the elevated concentrations of the vascular cell adhesion molecule (VCAM)-1. METHODS: Twenty primigravidas with preeclampsia were compared to 20 healthy primigravidas. Plasma levels of cytokines, tumor necrosis factor-alpha (TNF alpha), interleukin (IL)-6, IL-8, IL-1 beta, IL-1 receptor antagonist (IL-1ra), granulocyte macrophage-colony-stimulating factor (GM-CSF), and VCAM-1, were measured by enzyme-linked immunosorbent assay. RESULTS: Concentrations of IL-6 and IL-1ra were significantly higher (P < .01) in preeclamptic women (2.56 and 251.85 pg/mL, respectively) compared to normal pregnant patients (2.06 and 142.00 pg/mL, respectively). There were no significant changes in concentrations of TNF alpha, IL-8, GM-CSF, and IL-1 beta in preeclamptic patients (14.09, 50.52, 125.8, and 2.08 pg/mL, respectively) compared to normal patients (11.96 44.46, 121.3, and 2.01 pg/mL, respectively). Serum concentrations of VCAM-1 were increased in women with preeclampsia (preeclamptic group 841.9 +/- 49.7 ng/mL, control group 560.2 +/- 47.9 ng/mL; t = 3.673, P < .001). Interleukin-6 and IL-1ra concentrations correlated with VCAM-1 concentrations (IL-6: r = 0.539, z = 2.9, P < .005; IL-1ra: r = 0.451, z = 2.428, P < .02). CONCLUSIONS: Increased cytokine concentrations may contribute to the endothelial damage that occurs with preeclampsia and may explain the mechanism underlying leukocyte activation in this disorder. The increased cytokine concentration may also be responsible for the endothelial adhesion that accompanies preeclampsia.

Adult↗

PubMed1994

Mechanical stretch increases proto-oncogene expression and phosphoinositide turnover in vascular smooth muscle cells.

OBJECTIVE: To determine whether changes in haemodynamic load, simulated in vitro by mechanically stretching cultured vascular smooth muscle cells, could be transduced into biochemical signals similar to those produced by growth factors. DESIGN: A system was developed which was capable of stretching cultured vascular smooth muscle cells from 0 to 20%. The effect of stretching quiescent vascular smooth muscle cells on both c-fos messenger RNA (mRNA) expression and release of total inositol phosphates was determined over a time interval of 0-360 min. METHODS: Rat mesenteric artery vascular smooth muscle cells were grown using standard cell culture methods. Induction of the proto-oncogene, c-fos, was determined by Northern blotting. Phosphoinositide breakdown was assessed by measuring [3H]-inositol phosphates released from prelabelled cells. RESULTS: A 20% fixed stretch resulted in a rapid induction of c-fos mRNA which reached maximal levels by 15 min. The amount of c-fos mRNA detected was dependent on the degree of stretch, with maximum induction obtained for 15 and 20% stretch. The effects of mechanical stretch were also assessed on phosphoinositide turnover by measuring [3H]-inositol phosphates released from prelabelled cells. A 20% fixed stretch of vascular smooth muscle cells for 20 min resulted in a 3.2-fold increase in total [3H]-inositol phosphates released compared with unstretched cells. CONCLUSIONS: Our results show that mechanical stretch increases proto-oncogene expression and phosphoinositide turnover in vascular smooth muscle cells in vitro. These observations suggest that mechanical stretch and growth factors share common signal transduction pathways which may be important in the development of vascular hypertrophy.

Animals↗

PubMed1992

Angiotensin II increases proto-oncogene expression and phosphoinositide turnover in vascular smooth muscle cells via the angiotensin II AT1 receptor.

OBJECTIVES: The aim of this study was to determine which angiotensin II receptor (AT receptor) mediates proto-oncogene expression and phosphoinositide metabolism in vascular smooth muscle cells in vitro. DESIGN: The AT receptor antagonists DuP753 (losartan), an AT1 antagonist, and PD 123319, an AT2 antagonist, were used to characterize AT receptors on cultured vascular smooth muscle cells derived from the rat mesenteric artery and to identify which receptor subtype mediates the angiotensin II-induced increase in proto-oncogene expression and phosphoinositide metabolism. METHODS: Rat mesenteric artery vascular smooth muscle cells were grown using standard cell culture methods. Proto-oncogene induction was measured using Northern blotting. Phosphoinositide breakdown was assessed by measuring [3H]-inositol phosphates released from prelabelled cells. RESULTS: Receptor-binding studies revealed that the AT1 receptor predominated on vascular smooth muscle cells. Incubation of quiescent cells with 0.1 mumol/l angiotensin II resulted in a 65% increase in total [3H]-inositol phosphates released compared with unstimulated cells and in a rapid accumulation of c-fos messenger RNA (mRNA). Pre-incubation of the cells with 10(-5) mol/l PD 123319 had no effect on either total inositol phosphates release or c-fos mRNA induction. Both responses, however, were totally abolished by pre-incubation of the cells with 10(-5) mol/l losartan or saralasin. CONCLUSIONS: Angiotensin II acts through the AT1 receptor to increase c-fos expression and phosphoinositide turnover in vascular smooth muscle cells. These mechanisms may be important in angiotensin II-induced smooth muscle hypertrophy.

Angiotensin II↗

PubMed1990

Prevalence of human parvovirus (B19) and rubella virus infections in urban and remote rural areas in northern Brazil.

Sera from inhabitants of Belém, Pará (542 sera), Brazil and of members of 3 Brazilian tribes--Tiriyo/Alto Paru (near Surinam) (212 sera), Xicrin (128 sera), and Mekranoiti (121 sera)--of different age and sex groups were tested for the presence of specific antibody against human parvovirus (B19) (RIA) and rubella virus (latex agglutination test). Parvovirus (B19) IgG was found in 42.6% of the population sample from Belém but in only 4.7 to 10.7% of the members of the tribes. Rubella virus antibody was found in 72.7% of the sera from Belém but approaching a prevalence of 85-90% in age groups above 20 years. In the tribes rubella virus antibody was detected in 36.9 to 72.6% of all sera. There were remarkable sex differences of antibody prevalence in several age groups of the population from Belém and of the tribal populations. About a quarter of the skin rashes in Belém that were not attributable to infections with rubella, measles, or arboviruses were caused by recent B19 infections.

Adolescent↗

PubMed1985

Posterior fluorescein streaming.

Two patients with chronic branch retinal vein occlusions and recurrent vitreous hemorrhages were evaluated with fluorescein angiography. In both patients fluorescein studies revealed a unique pattern of superior fluorescein flow. Possible mechanisms for this process are discussed.

Aged↗

PubMedDate not supplied

Treatment of endothelial cells with serum from women with preeclampsia: effect on neutrophil adhesion.

OBJECTIVE: The purpose of our study was to determine whether the previously reported neutrophil activation that occurs in the maternal circulation of women with preeclampsia is due to a factor (or factors) in serum that increases neutrophil adhesion to endothelial cells. METHODS: The extent of neutrophil adhesion to endothelial cells incubated with serum from women with preeclampsia (n = 12) was compared with serum from normal, pregnant women matched for maternal age and gestational age at blood sampling (n = 12). Preeclampsia was defined as persistent diastolic blood pressure above 90 mmHg, with proteinuria greater than 0.3 g per 24 hours, in patients who were normotensive before 20 weeks' gestation. The ability of serum (with and without heat inactivation of the complement system) from both groups of patients to stimulate neutrophil adhesion to endothelial monolayers was tested in a 15-minute quantitative assay using fluorescence-labeled neutrophils. The extent of neutrophil adhesion was quantified indirectly from fluorescence counts. RESULTS: No significant differences were found regarding neutrophil-endothelial cell adhesion in response to media alone, serum from women with preeclampsia, and serum from normal, pregnant women. This was also the case when the serum was heat inactivated to destroy the complement system. However, heat inactivated serum produced a significantly greater extent of adhesion compared with serum containing an intact complement system, regardless of whether the patient had preeclampsia. CONCLUSION: This study found no evidence of a factor in serum from women with preeclampsia that could alter neutrophil-endothelial cell adhesion via a direct effect on the endothelium. However, our data suggest that adhesion may be regulated in an inhibitory manner by the complement system.

Adult↗