PubMed Health⌕ Search

Biomedical subjects

A M Oliver

Publications and source records attributed to A M Oliver.

At least 19 recordsLinked to original sources
PubMed2001

Antigen receptor proximal signaling in splenic B-2 cell subsets.

Splenic marginal zone (MZ) and follicular mantle (FO) B cells differ in their responses to stimuli in vitro and in vivo. We have previously shown that MZ cells exhibit greater calcium responses after ligation of membrane IgM (mIgM). We have now investigated the molecular mechanism underlying the difference in calcium responses following ligation of mIgM and studied the response to total B cell receptor ligation in these two subsets. We compared key cellular proteins involved in calcium signaling in MZ and FO cells. Tyrosine phosphorylation and activity of phospholipase C-gamma 2 and Syk protein tyrosine kinase were significantly higher in MZ cells than in FO cells after mIgM engagement, providing a likely explanation for our previous findings. Tyrosine phosphorylation of CD22 and expression of Src homology 2-containing inositol phosphatase and Src homology 2-containing protein tyrosine phosphatase-1 were also higher in the MZ cells. Expression and tyrosine phosphorylation of Btk, BLNK, Vav, or phosphatidylinositol 3-kinase were equivalent. In contrast, stimulation with anti-kappa induced equivalent increases in calcium and activation of Syk in the two subsets. These signals were also equivalent in cells from IgM transgenic, J(H) knockout mice, which have equivalent levels of IgM in both subsets. With total spleen B cells, Btk was maximally phosphorylated at a lower concentration of anti-kappa than Syk. Thus, calcium signaling in the subsets of mature B cells reflects the amount of Ig ligated more than the isotype or the subset and this correlates with the relative tyrosine phosphorylation of Syk.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2001

Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens.

The rate of pathogen elimination determines the extent and consequences of an infection. In this context, the spleen with its highly specialized lymphoid compartments plays a central role in clearing blood-borne pathogens. Splenic marginal zone B cells (MZ), by virtue of their preactivated state and topographical location, join B1 B cells to generate a massive wave of IgM producing plasmablasts in the initial 3 days of a primary response to particulate bacterial antigens. Because of the intensity and rapidity of this response, combined with the types of antibodies produced, splenic MZ and B1 B cells endowed with a "natural memory" provide a bridge between the very early innate and the later appearing adaptive immune response.

Animals↗
PubMed1999

IgMhighCD21high lymphocytes enriched in the splenic marginal zone generate effector cells more rapidly than the bulk of follicular B cells.

Ag encounter will recruit Ag-specific cells from the pool of mature B lymphocytes in the spleen and activate them to perform effector functions: generation of Ab-forming cells (plasma cells) and presentation of Ag to T cells. We have compared the ability of mature follicular and marginal zone cells to develop into effector B cells. The generation of marginal zone B cells and their localization in the marginal sinus area are T cell and CD40 ligand independent, suggesting that they do not represent a postgerminal center population. Compared with mature recirculating follicular B cells, they express several characteristics of previous antigenic experience, including higher levels of B7.1 (CD80) and B7.2 (CD86) when freshly isolated and following in vitro stimulation. After a brief 6- to 8-h in vitro stimulation with LPS or anti-CD40 Abs, marginal zone B cells become potent APCs. In addition, their ability to proliferate and differentiate into plasma cells in response to low doses of T-independent polyclonal stimuli (LPS) is far greater than that of follicular B cells. These findings indicate a functional heterogeneity within splenic mature B lymphocytes, with marginal zone B cells having the capacity to generate effector cells in early stages of the immune response against particulate Ags scavenged efficiently in this special anatomical site.

Animals↗
PubMed1999

Independently ligating CD38 and Fc gammaRIIB relays a dominant negative signal to B cells.

CD38 is expressed on a variety of hematopoietic cells and has a unique enzymatic activity that converts nicotinamide adenine dinucleotide (NAD) into cyclic ADP-ribose (cADPR) and then into ADPR. CD38 is expressed at increasingly higher levels on B cells at each stage of B cell differentiation, and is then down-regulated on germinal center B cells and mature plasma cells. Crosslinking of CD38 on the surface of mature, resting B cells induces B-cell proliferation, which is enhanced by co-signals such as IL-4 and LPS. CD38-induced proliferation is abrogated by Fc gammaRIIB ligation and this inhibition can be effected by the addition of anti-Fc gammaRII Ab midway through a 48 h in vitro culture indicating that it delivers a potent negative signal to CD38 activated B cells. The suppressive signal was shown to occur through the Fc gammaRIIB because CD38-induced B-cell activation was not inhibited by the ligation of Fc gammaRIIB in Fc gammaRII-deficient B cells. These results indicate that Fc gammaRIIB can act as a regulatory molecule that modulates CD38 signals in vivo.

ADP-ribosyl Cyclase↗
PubMed1997

Mouse CD38 is down-regulated on germinal center B cells and mature plasma cells.

Germinal center formation is the result of antigenic stimulation of B cells in a T cell-rich area. B cells cycle through the germinal centers, and a small percentage survive to become plasma cells or memory B cells. The transformation from a mature B cell into a germinal center B cell and finally into a terminally differentiated B cell is not well understood. Human CD38 is highly expressed on both germinal center B cells and plasma cells, and is useful in delineating these B cell subsets and in understanding the signaling events involved in the development of these B cells. To determine whether CD38 expression on activated germinal center B cells and postgerminal center B cells influences germinal center differentiation, we studied the expression of CD38 in the mouse. CD38 is expressed on follicular B cells in the Peyer's patches but is down-regulated on germinal center B cells located within the Peyer's patches. CD38dim/-B220+ germinal center B cells are also found in the spleens of immunized but not control mice, suggesting that Ag-stimulated germinal center formation is involved in the production of CD38dim/-B220+ B cells. Furthermore, mature plasma cells isolated from in vitro LPS cultures do not express CD38, but do contain high levels of cytoplasmic Ig. These results are in contrast to studies in humans in which CD38 is not found on follicular B cells but is highly expressed on germinal center B cells and plasma cells.

ADP-ribosyl Cyclase↗
PubMed1997

Marginal zone B cells exhibit unique activation, proliferative and immunoglobulin secretory responses.

Mouse splenic B cells can be separated based on their distinctive expression of cell surface antigens. Marginal zone (MZ) B cells are CD38high CD21high CD23low/-, while follicular (FO) B cells are CD21int CD23int and newly formed (NF) B cells are CD21dim/- CD23-. Exploiting these phenotypic distinctions, we isolated the three B cell subsets and assessed their other phenotypic differences and functional capabilities in vitro. FO B cells proliferate more than the other B cell subsets in response to either IgM or CD38 cross-linking. MZ B cells proliferate better than FO B cells when stimulated with lipopolysaccharide (LPS), sub-optimal levels of LPS and CD38 cross-linking or CD40 ligation. When NF, FO and MZ B cells were stimulated with either LPS or LPS and interleukin-4, MZ B cells secreted more IgM and IgG3 than the other two subsets. Similarly, calcium fluxes measured within MZ B cells are larger in amplitude and more sustained after B cell receptor cross-linking than those found in the other two subsets. Collectively, these results indicate that CD38high CD21high CD23low/- MZ B cells are specially suited to play a unique role in response to antigens delivered to the MZ area.

Animals↗
PubMed1994

The pulmonary artery catheter: a diagnostic adjunct for fat embolism syndrome.

Available objective tests for fat embolism are neither sensitive nor specific. We performed frozen-section analysis of blood aspirated from a pulmonary artery catheter in a trauma victim with fat embolism syndrome and found marked levels of pulmonary microvascular blood fat. The amount of fat detected in this patient with long bone fractures was higher than that observed in a pilot study of this technique in cardiopulmonary bypass patients. This technique provided diagnostic support of our clinical findings. The procedure may prove useful in patients with an equivocal diagnosis of fat embolism or when the cause of posttraumatic acute pulmonary insufficiency is unknown.

Aged↗
PubMed1994

Death from adult respiratory distress syndrome and multiorgan failure following acute upper airway obstruction.

In adults with acute epiglottitis, transient noncardiogenic pulmonary edema may follow relief of upper airway obstruction, but typically does not progress to more severe pulmonary derangements. We describe a patient with post-obstructive pulmonary edema whose course was complicated by ARDS, multiorgan failure, and death. Recognition of UAO and expedient treatment depends heavily on the judgment and skills of the clinician and the available resources of the institution. Physicians caring for patients with AE should be aware of the potential for delayed morbidity and mortality following upper airway obstruction, even after establishing an adequate artificial airway. This case provides additional justification for aggressive airway management and intensive care support of patients with AE in order to avoid serious complications.

Acute Disease↗
PubMed1991

Survival assessment of cultured epidermal allografts applied onto partial-thickness burn wounds.

Cultured epidermal allografts (C.E.A.) were applied to 6 partial thickness burns. Biopsies were obtained at intervals between 8-100 days after grafting. In the second week clinical re-epithelialisation of the allografted sites was confirmed histologically. Blood group- and sex-mismatch studies showed that the allografted cells were not present between 8-100 days post-grafting, suggesting that the newly formed epithelium was of host origin.

Adult↗
PubMed1991

The differentiation and proliferation of newly formed epidermis on wounds treated with cultured epithelial allografts.

Fifteen patients, eight with burn or scald wounds and seven with split-thickness donor sites, were treated with cultured epithelial allografts. Skin was obtained from HIV-negative donors undergoing circumcision and sheets of epithelium were cultured using the 3T3 feeder method. Multiple post-operative biopsies were performed at various time intervals and stained with a panel of monoclonal antibodies against cytokeratins, involucrin, transferrin receptor and epidermal growth factor receptor. Fresh cultured epithelial sheets, normal skin, standard treated donor sites and burns treated with autografts were also studied. Cytokeratin-10 expression was not observed at treated sites until 4 weeks post-grafting, when normal suprabasal levels were observed. Cytokeratins 13 and 16, usually observed in highly proliferative states such as psoriasis, were observed in epithelial-treated sites for up to 6 months. Other proliferation markers such as Ki67 and transferrin receptor were only expressed 2-3 weeks post-operatively. Involucrin, a marker of keratinocyte terminal differentiation, was expressed throughout newly formed epidermis until 15 weeks, when the normal pattern of granular expression was observed. These results indicate that although the cultured 'allograft' does not survive, it may modulate the proliferation and differentiation of spontaneously regenerating epithelium.

Adult↗
PubMed1991

Adhesion molecule expression in psoriatic skin lesions and the influence of cyclosporin A.

Normal skin of healthy individuals and both lesional and uninvolved skin from patients with psoriasis before and after receiving cyclosporin A (CsA; 2.5 or 5 mg/kg per day) was examined by immunocytochemistry for differences in expression of adhesion-relevant epitopes. Normal, lesional and uninvolved skin all showed staining of basal keratinocytes for CD29 (the common beta chain of the beta 1-integrin family). No other adhesion molecule investigated was detected on structural components of normal skin. In uninvolved skin, weak expression of CD54 (intercellular adhesion molecule 1, ICAM-1) was noted on vascular endothelium. Uninvolved keratinocytes were found to stain with anti-CD58 (leucocyte function-associated antigen 3, LFA-3) and there was weak expression of CD11b (alpha chain of complement C3bi receptor) and CD11c (alpha chain of p150, 95 molecule) but not CD11a (leucocyte function-associated antigen 1, LFA-1, alpha chain) on those cells. In lesional skin, in addition to expression of CD58, there was also enhanced expression of CD11c. Weak expression of CD54 on keratinocytes was also observed. Lesional blood vessels were found to stain strongly with anti-CD54, CD29 and CD58. CD11a was expressed only on infiltrating mononuclear cells. CsA treatment produced marked clinical improvement, accompanied by the loss of CD54 expression on keratinocytes. However, despite the loss of T cells from lesional skin with CsA treatment, CD54 persisted on blood vessels. CsA was found to have no effect on keratinocyte expression of CD29, CD58 or CD11b and c. The persistence of CD54 on vascular endothelium and of adhesion molecule expression on keratinocytes, despite resolution of the skin lesions, may explain the universal and rapid recurrence of psoriasis on cessation of CsA administration.

Adult↗
PubMed1990

The cytokeratin expression of cultured human foetal keratinocytes.

Skin samples taken from foetuses of 15-19 weeks gestational age and keratinocytes were cultured by the 3T3 feeder method or in serum-free MCDB 153 medium on 16 mm coverslips. Keratinocytes taken from paediatric circumcisions and patients undergoing plastic surgery were also cultured using the 3T3 feeder method. A panel of monoclonal antibodies against a number of cytokeratins and differentiation markers were used in the PAP technique to analyse the cells. Cryostat sections taken from the donor skin samples were stained simultaneously. Foetal skin expressed the cytokeratins 7, 13 and 19 that were not observed postnatally. This cytokeratin expression as maintained in both culture conditions and also observe in paediatric and adult keratinocytes. Cytokeratin 7 was expressed on a greater proportion of foetal cells than in vivo, whereas the expression of 13 and 19 decreased. All keratinocytes expressed vimentin, transferrin receptor and Ki67 (proliferating cell antigen), while a small proportion expressed involucrin throughout culture, indicating their high level of differentiation and proliferation. No differences were observed between low and high density cultures. Foetal keratinocytes cultured in MCDB 153 did not reach confluence and stronger staining of differentiation markers was observed in these cells. These results show that the in vivo differences in cytokeratin expression of foetal and adult keratinocytes disappear in the culture.

Cells, Cultured↗
PubMed1990

Macrophage heterogeneity in human fetal tissue. Fetal macrophages.

The immunophenotype of the macrophage population in human fetal tissue was studied, using a panel of monoclonal antibodies against cells of the macrophage/monocyte lineage. Using a double-labelling technique two main populations were observed in tissue from 14 weeks of estimated gestational age (EGA); EBM11+ DR+ and EBM11+ DR- cells of which a small proportion were also RFD7+. Most macrophages were negative with 3.9, an antibody specific for the adhesion molecule P150.95 and LP9 which is specific for a lysosomal enzyme. The exception to this was a small population of positive cells in the thymus. Small numbers of 3.9+ cells were also infrequently observed in tissue at and above 17 weeks of EGA, while occasional RFD9+ cells were only observed in most tissues, before this time. The higher percentage of macrophages were DR+ DQ- DP-, with a few DQ+ cells appearing at 15 weeks of EGA. In the thymus, DQ+ cells outnumbered DP+ cells especially in the medulla. These results indicate the heterogeneous and immature nature of the fetal macrophage population and point to the importance of age, tissue-specific factors and probable immune mediators in macrophage differentiation.

Antibodies, Monoclonal↗