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S Frimpong

Publications and source records attributed to S Frimpong.

7 recordsLinked to original sources
PubMed2003

HIV infection of women in African countries.

BACKGROUND: The increase in human immunodeficiency virus infection among women of childbearing age increases the potential risk for vertical transmission of infection to their newborns. AIM: This paper discusses literature reviewed on human immunodeficiency virus infection of women in Africa with reference to Ghana, West Africa. The paper provides an epidemiological overview of human immunodeficiency virus infection of women in Ghana and Africa and the potential risk for vertical transmission and associated contributing factors. Literature reviewed was retrieved from the Cumulative Index of Nursing and Allied Health Literature and United States National Library of Medicine databases. CONCLUSION AND IMPLICATIONS FOR PRACTICE: Findings from the review of literature suggest that human immunodeficiency virus infection of African women is a major public health problem which must be addressed and considered a priority in the next decade. Leadership in African countries including nurses and policy-makers will have to do more to make a difference to the epidemic. Measures to reduce transmission of human immunodeficiency virus are discussed.

Africa↗
PubMed2000

Selectins (CD62L, CD62P) and megakaryocytic glycoproteins (CD41a, CD42b) mediate megakaryocyte-fibroblast interactions in human bone marrow.

Previous in vitro studies are in keeping with the finding that isolated and enriched megakaryocytes attach to bone marrow fibroblasts and generate an increased growth of these cells. This process was assumed to depend on a close spatial relationship between both cell types which supports the paracrine effect of platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-beta1. Moreover, adhesion molecules including beta1 integrin receptors and fucosylated structures were determined to play an important role in these complex interactions. However, up to now the influence of megakaryocyte expressed glycoproteins CD41a and CD42b in these processes was not investigated. In addition, the role of megakaryocytic CD62P and also of CD62L, both adhesion molecules of the selectin group, could also be of interest. Following isolation and enrichment of bone marrow megakaryocytes and fibroblasts, both cell populations were characterized regarding their expression of these factors by applying immunocytochemical techniques. Additionally, their influence on adhesion of megakaryocytes to fibroblasts as well as fibroblast growth was evaluated by comparative megakaryocyte-fibroblast co-cultures and inhibition studies using specific monoclonal antibodies (mabs). Fibroblast monocultures served as controls. In these experiments, selectin-specific antibodies significantly reduced megakaryocyte attachment to fibroblast feeder layers and fibroblast growth in the co-cultures. The effect of CD41a and CD42b specific antibodies was limited to megakaryocyte-dependent fibroblast growth. These results elucidate the involvement of the selectins CD62P and CD62L in the basal activation of megakaryocytes inducing their attachment to bone marrow fibroblasts. In contrast, the megakaryocyte glycoproteins CD41a and CD42b exert their effect on the megakaryocyte dependent fibroblast growth. Altogether, it is tempting to speculate that the various interactions of these mediators reflect certain steps in the complex pathomechanisms causing the evolution of (reactive) myelofibrosis in hematopoietic neoplasias accompanied by megakaryocytic proliferation.

Bone Marrow↗
PubMed1999

Polycythemia vera megakaryocytes store and release lysozyme to a higher extent than megakaryocytes in secondary polycythemia (polyglobuly).

Lysozyme, a myelomonocytic marker not only exerts bacteriolytic, but also immunomodulatoric properties and was found to bind to the glycosaminoglycan serglycin, an important constituent of the extracellular matrix (ECM). Pathological serum lysozyme levels were described in chronic myeloproliferative disorders (CMPDs) and other hematological conditions. In this context it is remarkable that in polycythemia rubra vera (PV), characterized by a proliferation particularly of the megakaryo- and erythropoiesis, serum lysozyme levels behave independently of the numbers of myelomonocytic cells in peripheral blood. To elucidate whether megakaryopoiesis might be the source of the increased serum lysozyme, we performed an experimental study on isolated and enriched megakaryocytes derived from bone marrow of patients with PV. Findings were compared to a group of patients with reactive (smoker's) polyglobuly (PG). In confirmation of previous results, quantification of serum lysozyme levels showed a slight elevation in the cohort of PV patients which was not correlated with the leukocyte count. Applying an immunohistochemical assay we were able to demonstrate intracytoplasmic lysozyme storage in megakaryocytes. Moreover, performing the reverse hemolytic plaque assay (RHPA), a technique which enables detection of secreted proteins at the single cell level, we found that 54% of the PV, but only 3% of the PG megakaryocytes spontaneously secreted lysozyme. After rhIL-3 treatment the secretion of lysozyme remained unchanged in PV but increased to 14% in PG. These findings suggest that the extent of megakaryocytic lysozyme secretion might discriminate PV from reactive conditions. Although a direct involvement of lysozyme in the regulation of aberrant megakaryopoiesis in PV is not likely, the results of the present study point to the possibility that lysozyme could be involved in the interactions of PV megakaryocytes with ECM. Moreover, the response to rhIL-3 significantly discriminates PV megakaryocytes from megakaryocytes of the PG group.

Female↗
PubMed1999

Megakaryocyte induced fibroblast proliferation is enhanced by costimulation with IL-6/IL-3 and dependent on secretory and adhesion events.

Experimental data are in keeping with the finding that megakaryocytes isolated from normal human bone marrow may promote fibroblast growth. This effect can be significantly enhanced by interleukin (IL)-3. In this context it has been demonstrated that IL-3 induces the release of platelet-derived growth factor (PDGF) and transforming growth factor beta1 (TGFbeta1) from megakaryocytes, factors known to enhance fibroblast proliferation. The present in vitro study was performed to elucidate the action of several other cytokines which are able to influence the different steps of megakaryocyte maturation and function like stem cell factor (SCF), IL-6, and leukemia inhibitory factor (LIF) as well. Following an appropriate experimental design we were able to show that none of the mentioned cytokines enhanced megakaryocyte dependent fibroblast proliferation in the coculture assays. On the other hand, IL-6 in combination with IL-3 surpassed the IL-3 dependent action significantly. However, the combined IL-3/IL-6 effect was not explainable by an increased PDGF/TGF-beta secretion of the megakaryocytes. In transwell experiments the inhibition of cell-to-cell contact via tissue culture inserts generated a conspicuous impairment of fibroblast growth in the IL-3/IL-6 treated cocultures. This reversal surpassed even the effect on the untreated and IL-3 stimulated cocultures. Hence, a direct contact of both cell types probably inducing adhesion phenomenons and warranting a certain threshold of local PDGF/TGF-beta concentration is a prerequisite for the proliferative effect on fibroblasts in the costimulation experiments. These results are of special interest regarding the evolution of myelofibrosis in chronic myeloproliferative disorders (CMPDs) because (1) various progenitor cells including the megakaryocytic lineage are hypersensitive towards IL-3 and (2) an abnormal secretion of IL-6 is described for megakaryocytes in these disorders.

Cell Adhesion↗
PubMed1999

Polycythemia vera megakaryocytes but not megakaryocytes from normal controls and patients with smokers polyglobuly spontaneously express IL-6 and IL-6R and secrete IL-6.

Polycythemia rubra vera (PV) represents a clonal hematological disorder defined by an abnormal expansion of erythroid precursors and megakaryopoiesis, in particular. Ample evidence has been provided that the IL-6/1L-6R complex may be responsible for the proliferation of normal and neoplastic megakaryocytes in vitro and this fact lead us to the hypothesis, that defects in the regulation of IL-6 synthesis take part in the pathogenesis of PV. The study was carried out to determine the IL-6 serum levels and the megakaryocytic IL-6 production in patients with PV and to compare these data with the situation in hematologically healthy donors as well as in patients suffering from spurious polycythemia--smokers polyglobuly (PG). For this purpose, IL-6 serum levels were measured by ELISA and the megakaryocytic production studied by immunohistochemistry, reverse hemolytic plaque assay (RHPA) together with reverse transcription/polymerase chain reaction (RT-PCR) in highly enriched megakaryocyte preparations. In additional experiments, the influence of IL-3 stimulation and the expression of IL-6R were tested. Serum levels of IL-6 did not differ between the three groups under study. In contrast, immunohistochemistry revealed a raised proportion of megakaryocytes expressing IL-6 in PV as compared to normal donors and patients suffering from PG. The percentage of megakaryocytes actively secreting this cytokine as detected by the RHPA was 20 times greater than in both the other groups. This phenomenon was further substantiated by the fact that IL-6 mRNA could only be shown in PV megakaryocyte preparations. The regulation of IL-6 secretion appears to be abnormal in PV. Whereas in the normal and in the PG group IL-3 stimulation exerts a marked increase in megakaryocytic IL-6 secretion, PV megakaryocytes responded with a paradoxical down-regulation of IL-6 synthesis combined with the loss of IL-6R. Our data describe for the first time an abnormally raised IL-6 production by PV megakaryocytes and point towards fundamental regulatory alterations of the IL-6 synthesis in this disease.

Bone Marrow↗
PubMed1998

Evidence for integrin receptor involvement in megakaryocyte-fibroblast interaction: a possible pathomechanism for the evolution of myelofibrosis.

Megakaryocytes are assumed to be functionally linked with the evolution of myelofibrosis, complicating chronic myeloproliferative disorders. It has already been shown that megakaryocytes will promote fibroblast growth in vitro when in spatial proximity. Here, we demonstrate that the integrin receptors alpha3beta1 and alpha5beta1 are involved in this megakaryocyte-fibroblast interaction. Upon addition of anti-alpha3 and -alpha5 antibodies to megakaryocyte-fibroblast cocultures, fibroblast growth was significantly impaired, and megakaryocyte attachment to the fibroblast feederlayer was significantly reduced. Unilateral blocking of megakaryocytes with anti-alpha3 or -alpha5 antibodies resulted in a suppression of adhesion, probably reflecting the prominent function of fibronectin receptors on the megakaryocyte surface. Moreover, the oligopeptide RGDS (Asp-Gly-Asp-Ser) caused a significant reduction of fibroblast growth as well as megakaryocyte adhesion. This feature reinforces that fibronectin receptors are involved. In addition, fibroblast proliferation was impaired by the application of fibronectin antibodies recognizing the cell-binding domain. However, no effect was observable with respect to megakaryocyte adhesion. In conclusion, our in vitro studies demonstrate the involvement of beta1-integrins, in particular the fibronectin receptor in the megakaryocyte-dependent fibroblast proliferation and therefore suggest a pivotal role of megakaryocytes in the complex pathomechanism causing myelofibrosis.

Adult↗