PubMed Health⌕ Search

Biomedical subjects

S E Ferguson

Publications and source records attributed to S E Ferguson.

15 recordsLinked to original sources
PubMed2003

Heparin for pregnant women with acquired or inherited thrombophilias.

BACKGROUND: Thrombophilias, which are associated with a predisposition to thrombotic events, have been implicated in adverse obstetrical outcomes such as intrauterine growth restriction, stillbirth, severe early onset pre-eclampsia, and placental abruption. Heparin administration in pregnancy may reduce the risk of these events. OBJECTIVES: The objective of this review was to assess the effects of heparin on pregnancy outcomes for women with a thrombophilia. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (July 2002), MEDLINE, EMBASE, CINAHL, Scidex (via OVID Technologies - July 2002) and reference lists and personal files. SELECTION CRITERIA: Randomized controlled trials comparing heparin with placebo or no treatment, or randomized controlled trials comparing any two treatments. Quasi randomized studies would be included. DATA COLLECTION AND ANALYSIS: Data would be abstracted from identified studies and recorded on a paper form by two reviewers. MAIN RESULTS: No studies were included. REVIEWER'S CONCLUSIONS: There are no completed trials to determine the effects of heparin on pregnancy outcomes for women with a thrombophilia.

Anticoagulants↗
PubMed2001

Maternal plasma homocysteine levels in women with preterm premature rupture of membranes.

Homocysteine is a sulfur-containing amino acid produced by the breakdown of methionine. Plasma homocysteine levels can be elevated due to a variety of genetic and nutritional factors. Poor nutrition from diets low in folate and vitamin B12 can lead to hyperhomocysteinemia. Mildly elevated levels of homocysteine have been implicated in a number of disease processes such as atherosclerotic vascular disease and adverse obstetrical outcomes. High levels of plasma homocysteine are also associated with abnormal collagen cross-linking. Due to homocysteine's effects on connective tissue integrity, it is hypothesized that hyperhomocysteinemia in pregnancy is associated with preterm premature rupture of membranes (PPROM). Hyperhomocysteinemia, therefore, could be a treatable cause of this important public health concern.

Amino Acid Metabolism, Inborn Errors↗
PubMed1999

The effects of different culture media, glucose, pyridine nucleotides and adenosine on the activity of 11beta-hydroxysteroid dehydrogenase in rat Leydig cells.

11Beta-hydroxysteroid dehydrogenase (11betaHSD) reversibly converts glucocorticoids into inert 11-ketosteroids. The direction of the reaction has been found to vary with the cell type and sub-cellular preparation used. We have investigated if the directionality of 11betaHSD can be influenced by the nature of the culture medium and compounds added during incubation of rat testis Leydig cells. We found that when the cells were cultured in Dulbecco's Modified Eagle Medium (DMEM) that the dehydrogenase (11betaDH) activity was higher than the reductase (11KSR) activity (11betaDH:11KSR ratio approximately 2:1). When glucose was omitted from the DMEM a higher 11betaDH:11KSR ratio (approximately 33:1) was obtained. However, when the cells were cultured in a combination of DMEM/Ham's F12 (1:1, v/v), a ninefold increase in 11KSR activity was obtained whereas 11betaDH activity was inhibited by 64% compared with cells incubated in DMEM alone. Consequently, the predominant activity changed from a dehydrogenase to a reductase (11betaDH:11KSR ratio 1:15). Addition of the individual components of the Ham's F12 medium to DMEM showed that only pyruvate and/or the amino acids were able to mimic the effects of DMEM/Ham's F12. Similar differential effects were found when NAD+, NADH or adenosine were added to the Leydig cells incubated in DMEM (three to fivefold increases and 20-50% decreases in 11KSR and 11betaDH activities, respectively). In contrast, NADP+ was found to increase 11betaDH activity (up to threefold) but NADPH had no effect on 11KSR activity. Cells incubated with DMEM/Ham's F12, NAD+, NADP+ and adenosine were found to have higher ATP levels (four to sixfold) than those incubated in DMEM alone. These results illustrate that the relative 11betaDH and 11KSR activities of 11betaHSD in Leydig cells are markedly and differentially altered by the nature of the incubation medium and compounds added.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed1996

CD28 is required for germinal center formation.

Previous studies have demonstrated that the T cell costimulatory molecule, CD28, is important in the development of humoral immunity. CD28-deficient mice exhibit defects in isotype switching and are more susceptible to pathogens that depend on an effective Ab response. To determine the basis of these defects, we have examined B cell responses of CD28-deficient mice at the microenvironmental level. Early in a normal T-dependent immune response, small numbers of B cells undergo activation in the T cell-rich zone of secondary lymphoid tissues and then migrate to B cell areas. These migrant B cells found developing germinal centers by proliferative expansion, during which individual cells acquire mutations in their rearranged Ig genes. B cell mutants retaining higher affinities for Ag undergo positive selection in germinal centers, resulting in the establishment of the memory B cell compartment. In the present study, we demonstrate that although potentially Ag-reactive cells within the lymphoid follicle accumulate following antigenic challenge, these cells fail to undergo proliferative expansion to form germinal centers and do not acquire somatic mutations in CD28-deficient animals. Thus, the CD28 activation pathway is required for Ab responses to T-dependent Ags. cell compartment. In the present study, we demonstrate that although potentially Ag-reactive cells within the lymphoid follicle accumulate following antigenic challenge, these cells fail to undergo proliferative expansion to form germinal centers and do not acquire somatic mutations in CD28-deficient animals. Thus, the CD28 activation pathway is required for Ab responses to T-dependent Ags.

Animals↗
PubMed1994

Regulation of RAG-2 protein expression in avian thymocytes.

The recombinase-activating genes, RAG-1 and RAG-2, have been shown to be necessary to initiate the process of V(D)J recombination during the ontogeny of lymphocytes. While much is known about the end products of this rearrangement process, little is known about the function or regulation of the components of the recombinase system. To this end, we have generated a monoclonal antibody to the chicken RAG-2 protein. Chicken thymocytes were found to express high levels of RAG-2, part of which is phosphorylated. Within thymocytes, RAG-2 is expressed primarily within the nucleus. RAG-2 protein levels are high in the CD4- CD8- and CD4+ CD8+ immature thymocytes but absent at the single-positive CD4+ CD8- or CD4- CD8+ stage of thymocyte development. Mitogenic stimulation of thymocytes with phorbol myristate acetate and ionomycin results in down-regulation of RAG-2 expression. Consistent with these data, in vivo levels of RAG-2 are markedly lower in proliferating thymocytes than in smaller, G0/G1 cells. Down-regulation of RAG-2 expression appears to occur before cells enter S phase, suggesting that RAG-2 function may be limited to noncycling cells.

Animals↗
PubMed1993

Peripheral B cell maturation. II. Heat-stable antigen(hi) splenic B cells are an immature developmental intermediate in the production of long-lived marrow-derived B cells.

HSAhi B cells comprise 5 to 10% of adult mouse splenic B cells and are phenotypically and functionally immature. To assess their origin and relationship to mature, heat-stable Ag (HSA)lo B cells, we determined HSA and surface IgD phenotype among splenic B cells throughout development, as well as during reconstitution of lethally irradiated adults given adult B-depleted bone marrow. In each case, HSAhi splenic B cells predominate during the earliest stages of B cell genesis. Furthermore, 5-bromo-2'-deoxyuridine labeling experiments indicate rapid turnover within both the marrow and peripheral HSAhi pools, and adoptive transfer studies show that peripheral HSAhi splenic B cells differentiate to HSAlo within 4 days. Finally, splenic HSAhi B cells reconstitute both primary and memory humoral responses. Together, these data indicate that splenic B cells in the HSAhi subset are an intermediate maturational stage in the adult periphery.

Animals↗
PubMed1993

Arachidonic acid metabolism in cells transfected with sense and anti-sense cDNA to annexin I.

Thymic epithelial cell line TEA3A1 produce prostaglandin E2 (PGE2) and express high levels of annexin I. In order to study the relationship between the levels of annexin I expression and the arachidonic acid metabolism, TEA3A1 cells transfected with expression vector containing full length annexin I cDNA in either sense or anti-sense orientation was studied. In the anti-sense cells where the level of annexin I was reduced, the PGE2 production was significantly lower. On the other hand, PGE2 production was significantly higher in sense cells where the production of annexin I was also higher than in control cells. Our results show that increased PGE2 production in sense cells was accompanied by higher levels of PLA2 enzymatic activities. These results suggest that the production of annexin I is positively associated with the phospholipase A2 enzymatic activity and the prostaglandin production in thymic epithelial cells.

Animals↗
PubMed1992

Peripheral B cell maturation. I. Immature peripheral B cells in adults are heat-stable antigenhi and exhibit unique signaling characteristics.

Whether recently generated peripheral B cells in adults are functionally equivalent to immature B cells in the neonatal spleen is unknown. We have identified a splenic B cell subpopulation in adults whose phenotypic and in vitro characteristics closely resemble those of neonatal B cells. These cells are defined by the cell surface phenotype heat-stable Aghi (HSAhi), and make up 10 to 15% of the adult splenic B cell pool. HSAhi B cells in adults bear the immature phenotype B220lo sIgMhi, and are 50% sIgD+. Furthermore, after sublethal irradiation, the initial wave of newly generated splenic B cells in self-reconstituting adults express a similar phenotype. In keeping with previous data on neonatal B cells, HSAhi cells from either normal or self-reconstituting mice are refractory to stimulation with anti-IgM antibodies, yet proliferate upon LPS stimulation, and generate primary antibody responses if given appropriate T cell help. In contrast to neonatal cells, HSAhi adult B cells are refractory to stimulation with PMA plus ionomycin. Together, these data suggest that peripheral HSAhi B cells in adults correspond to recently generated B cells, whose signaling characteristics are distinct from previously described B cell subsets.

Animals↗
PubMed1991

Layered collagen fabric of cerebral aneurysms quantitatively assessed by the universal stage and polarized light microscopy.

We evaluated the effectiveness of the Universal stage, an instrument for measuring three-dimensional orientation of birefringent materials, for studying the collagen fabric in the wall of brain aneurysms. Vessels from autopsy were fixed at normal arterial distending pressure with 10% formalin, and prepared for polarized light microscopy, with paraffin embedding and staining with picrosirius red for birefringent enhancement. Quantitative data were obtained from tangential and oblique sections (7 microns thickness) of an intact 8 mm aneurysm, a 1.5 mm aneurysm, and a tangential section (3 microns thickness) of a cerebral artery. Sections of full-size aneurysms seen through the microscope, adjusted either for plane or circularly polarized light, revealed distinctive layers of collagen across the aneurysmal wall, which at higher magnification were further subdivided. Three-dimensional measurements, numbering 1,082, were made by use of the Universal stage attachment to the polarizing microscope. They were plotted by computer-controlled graphics on Lambert projections and analyzed by circular statistics. When assessed layer by layer, the collagen spanned a full range of orientations relative to the tangential plane. The circular standard deviation, a measure of the spread of alignment about the mean, was as low as 10 degrees for coherently organized collagen and as high as 40 degrees for the least coherently organized collagen, values characteristic of either the organized tunica media, or the least organized tunica adventitia of cerebral arteries. Although there was a marked thinning of the wall of one aneurysm, there was no evidence of structural weakness based only on the directional organization assessed by our measurements.

Autopsy↗
PubMed1989

Analysis of a novel VHS107 haplotype in CLA-2 and WSA mice. Evidence for gene conversion among IgVH genes in outbred populations.

Gene conversion has been suggested as the basis for many VH allelic differences, particularly in the murine VHS107 family. Whether conversion among IgVH genes is likely to have occurred in outbred populations has not been directly addressed. The CLA-2/Cn and WSA strains, which were recently and independently derived from a feral population exhibiting low responsiveness to PC, provide the opportunity to approach this question. In previous studies, the heavy chain cDNA sequence of a PC-specific hybridoma derived from CLA-2/Cn suggested gene conversion events within the VHS107 family. Accordingly, we have examined the germline VHS107 genes of CLA-2/Cn and WSA. The results indicate that: (a) The CLA-2 and WSA strains bear an identical but novel VHS107 family haplotype, which lacks a V3 element and contains a V1, a V13, and two V11 genes; (b) low PC responsiveness in these populations is unlikely due to an inability to express the V1 member of the VHS107 gene family; and (c) when compared with the other known VHS107 haplotypes, the proportion of differences consistent with gene conversion greatly exceeds that expected by random base substitution. Thus, gene conversion events appear to have occurred with considerable frequency in the evolution of the murine VHS107 family, especially among the V3, V13, and V11 members.

Alleles↗
PubMed1988

Interaction and sequence diversity among T15 VH genes in CBA/J mice.

Nucleotide sequences of the four genes composing the T15 heavy chain variable region (VH) family of the CBA/J mouse have been determined. Comparison of these sequences with their published BALB/c and C57BL/10 homologues reveals that nucleotide differences found between given alleles of two strains, i.e., CBA/J and BALB/c, are observed in other family members of the same strain. We suggest that these patterns of sequence variation are most readily explained by gene interaction (conversion). Additionally, the sequence of a CBA/J hybridoma, 6G6, proposed to have been generated by gene conversion, is directly encoded by the CBA/J V11 gene indicating that the putative conversion has occurred meiotically in the germline. These results are consistent with the premise that gene correction is occurring frequently among members of this family and that such processes may contribute significantly to the evolution of Ig variable region genes even in the relatively short time frame of inbred strain derivation.

Alleles↗
PubMed1983

Properties of porcine liver and testicular steroid sulphotransferases: reaction conditions and influence of naturally occurring steroids and steroid sulphates.

Sulphotransferase activity has been assayed in porcine liver and testis cytosol using either 3'-phosphoadenosine-5'-phospho [35S]sulphate (PAPS) or unlabelled PAPS as sulphate donors. In porcine liver the sulphotransferase for DHA was linear for up to 10 min, the optimum pH was 7.7 and optimum temperature, 37 degrees C. The apparent Km value was found to be 91 mumol/l and the activity was inhibited non-competitively by 5 alpha-androst-16-en-3 beta-yl sulphate, with all concentrations used (0.02-25 mumol/l) inhibiting the enzyme to the same extent. Time courses for sulphoconjugation of pregnenolone and 5 alpha-androst-16-en-3 beta-ol were linear for up to at least 10 min or up to only 5 min, respectively. The optimum pH values and temperatures were pH 8.0 and 37 degrees C in each case. The porcine testicular sulphotransferase activity for DHA as substrate was linear with time up to 10 min, the apparent Km for the reaction was 2 mumol/l and apparent Vmax 10 nmol/l/mg/min. 5 alpha-Androst-16-en-3 beta-yl sulphate (11.3-45.2 mumol/l) failed to inhibit the enzyme activity. The time-course for the reaction, when pregnenolone was used as substrate, was also linear up to 10 min at the optimum pH 8.0 but, in contrast to the reaction when DHA was the substrate, had an apparent Km of 20 mumol/l and was inhibited by pregnenolone sulphate, 5 alpha-androst-16-en-3 beta-yl sulphate, DHA and 5 alpha-androst-16-en-3 beta-ol, but not by DHA sulphate. 5 alpha-Androst-16-en-3 beta-yl sulphate inhibited the reaction non-competitively and to the same extent at concentrations over the range 11.3-45.2 mumol/l. These data suggest that DHA and pregnenolone may not be sulphoconjugated by the same sulphotransferase. With 5 alpha-androst-16-en-3 beta-ol as substrate, the time-course for its sulphate formation was linear up to 15 min, and this reaction could explain the quantities of 5 alpha-androst-16-en-3 beta-yl sulphate that are found endogenously in porcine testis. Our results further suggest that these quantities could well inhibit the sulphation of pregnenolone in porcine testis in vivo, and the possibility of control of sulphoconjugation in this tissue is discussed. Having regard to the smaller quantities of 5 alpha-androst-16-en-3 beta-yl sulphate present in porcine liver, our results suggest that the sulphation of DHA there may not be so much affected.

Androstenols↗
PubMed1982

Sulphoconjugation of steroids in porcine liver. Partial purification of the cytosolic sulphotransferases for pregnenolone and 5 alpha-androst-16-en-3 beta-ol.

Steroid sulphotransferase activities for 5 alpha-androst-16-en-3 beta-ol and pregnenolone in porcine liver cytosol have been assayed using 3'-phosphoadenosine-5'-phospho[35S]sulphate as sulphate donor. 5 alpha-Androst-16-en-3 beta-ol sulphotransferase activity was obtained from porcine liver cytosol by gel filtration chromatography; activity was linear with time up to about 5 min., the optimum pH was near 8.0 and optimum temperature 37 degrees C. Pregnenolone sulphotransferase activity was partially purified from porcine liver cytosol using DEAE-cellulose chromatography with an ionic gradient of KC1. This enzyme activity was linear with time up to 10 min and had optimum pH and temperature of 8.0 and 37 degrees C, respectively.

Animals↗