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Biomedical subjects

P Simmons

Publications and source records attributed to P Simmons.

At least 55 records · Page 3Linked to original sources
PubMed1990

Mechanisms of cytomegalovirus-mediated myelosuppression: perturbation of stromal cell function versus direct infection of myeloid cells.

Infection with cytomegalovirus (CMV) continues to be one of the most common complications following allogeneic bone marrow transplantation. To study the role of CMV in the suppression of hemopoiesis that frequently accompanies infection, we investigated the effect of CMV on the growth of isolated committed myeloid progenitors and on hemopoiesis in long-term bone marrow cultures. Laboratory strain AD169 had no effect on the growth and development of progenitor cells. In contrast, 40% of clinical isolates of CMV inhibited colony formation by up to 100%. In long-term bone marrow cultures all CMV isolates resulted in myelosuppression, which in the majority of cases was associated with the infection of stromal elements. Analysis of RNA from stromal cells infected with AD169 and one clinical isolate demonstrated a specific deficiency of granulocyte colony-stimulating factor transcripts. For a small proportion of the clinical isolates tested in long-term bone marrow cultures, suppression of hemopoiesis was correlated with infection of developing granulocytes. These studies suggest that CMV can impair hemopoiesis either through infection of stromal cells and consequent perturbation of growth factor production or by direct infection of myeloid cells.

Antigens, Viral↗
PubMed1989

A technique for spot application of fibrin glue during open heart operations.

Several techniques have been described for preparing and applying fibrin glue to control surgical bleeding. However, these methods tend to be cumbersome, expensive, or messy. Furthermore, commercial kits have not been approved by the Food and Drug Administration because of the potential risk of hepatitis contamination. Therefore, we have devised a modified, simpler technique that enables the precise, pinpoint application of fibrin glue. The risk of hepatitis transmission is substantially reduced by using cryoprecipitate plasma instead of fibrinogen from pooled donors. This technique is especially well suited for anastomoses of small vessels or for sealing suture holes in nonporous grafts.

Aprotinin↗
PubMed1988

Quantitative evaluation of real-time ultrasound features of the breast.

Semi-quantitative diagnostic features were extracted by a visual analysis of the echographic images of selected cases of breast disease and the results stored in a computer database. The long term aim is to create an environment suitable for the use of multivariate statistical methods systematically to evaluate ultrasound interpretive criteria and diagnostic performance in relation to factors such as scanning instrumentation and other diagnostic techniques. Eventually it is hoped that it will be possible to generate a system for computer assisted diagnosis and training. The results of this pilot study serve to demonstrate the feasibility of the approach and a univariate analysis is used to provide a preliminary ranking of diagnostic features. Features found to be particularly valuable for distinguishing benign from malignant solid lesions were the regularity and definition of the edge of the tumour, the mobility of the tumour and measures of echo heterogeneity within and posterior to the tumour mass.

Breast↗
PubMed1987

Cellular interactions and genetic restriction.

These studies emphasize the limitations of in vitro colony assays utilizing heterogeneous cell populations for the identification of cell-cell interactions that may involve genetic restriction. Obviously, different strategies are required to determine if Class II molecules have any role, alone or in combination with other determinants, in mediating hematopoietic cell-cell interactions. In this report, we present preliminary data derived from two approaches designed to address this issue. First, clonal cell lines developed to mimic Class II expression of normal precursors have been used to study structure-function relationships of HLA-D region gene products. Second, the lymphocyte adhesion assay has been adopted to study binding of precursors to marrow stroma. We hypothesize that the strategies should make it possible to identify hematopoietic cell-cell interactions and determine to what extent Class II molecules participate in these interactions.

Animals↗
PubMed1986

Perturbed hemopoiesis and the generation of multipotential stem cell clones in src-infected bone marrow cultures is an indirect or transient effect of the oncogene.

Multipotential stem cell lines, derived specifically from long-term bone marrow cultures infected with a recombinant retrovirus carrying v-src, lack v-src. Stable consequences thus result from transient actions or indirect effects of v-src on other cells, with the latter possibility being favored by its mosaic expression in marrow cultures.

Animals↗
PubMed1985

The role of stromal cells and growth factors in haemopoiesis and modulation of their effects by the src oncogene.

In the haemopoietic system the mature blood cells have only a finite lifetime. For example, a circulating granulocyte in the peripheral blood has an approximate half-life of 7 h (Cartwright, Athens & Wintrobe, 1964; Dancey, Dubelbeiss, Harker & Finch, 1976) whilst the lifetime of an erythrocyte is approximately 120 days (Wickramasinghe & Weatherall, 1982). This constant 'death' of mature functional haemopoietic cells means that new blood cells must replace those that are removed. The process of haemopoiesis provides the mature functional blood cells to replace those lost as a consequence of performing their biological functions (e.g. lymphocytes and macrophages in the immune response) or through apparent old age and breakdown (e.g. erythrocytes that are 110-120 days old). The major questions that we are required to answer about this process are 'where do all these new cells come from?', 'what regulates their production?' and 'how is this mechanism of control lost in haemopoietic disorders such as leukaemia, hyperproliferative diseases and anaemias?'. Recent work in the field of haemopoiesis has given some clues to the answers to the questions, which provide an intriguing insight into not only haemopoiesis itself but the possible lesions associated with the various blood disorders.

Animals↗
PubMed1984

Hepatitis B core antigen synthesised in Escherichia coli: its use for antibody screening in patients attending a clinic for sexually transmitted diseases.

Hepatitis B core antigen (HBcAg) synthesised in Escherichia coli by recombinant DNA techniques was compared with HBcAg prepared from infected liver tissue. The two antigens were used in radioimmunoassays (RIA) to detect antibody to HBcAg (anti-HBc) in sera from patients attending a clinic for sexually transmitted diseases. Out of 2151 sera tested, 260 were anti-HBc positive with both HBcAg preparations but seven were positive with the liver-derived antigen alone. Reasons for these discrepant results are discussed. The slight loss of sensitivity of the anti-HBc RIA using E. coli HBcAg was not considered significant when compared with the potential advantages of a synthetic antigen. The presence of other hepatitis B markers in the 267 anti-HBc positive sera was determined: 25 contained HBsAg, 220 anti-HBs and, of the 22 that were HBsAg/anti-HBs negative, 12 contained anti-HBe. In the 10 remaining sera, anti-HBc was the only hepatitis B marker that could be found.

Escherichia coli↗
PubMed1984

Glucose production and utilization in children with glycogen storage disease type I.

Glucose turnover rates were estimated with [2H2]glucose in five children with glycogen storage disease type I (GSD I) during sequential withdrawal of an infusion of glucose to determine whether their hypoglycemia was the result of decreased glucose production or increased rates of glucose utilization. Plasma glucose concentrations were 78 +/- 5 mg/dl during infusion of glucose at 6 mg X kg-1 X min-1 and decreased to 53 +/- 3 and 45 +/- 7 mg/dl during the 3 and 1.5 mg X kg-1 X min-1 glucose infusions, respectively. Total glucose flux during the 6 mg X kg-1 X min-1 glucose infusion was 7.3 +/- 0.7 mg X kg-1 X min-1 and decreased with reduction in the rate of glucose infused. Endogenous glucose production increased with each decrease in the rate of exogenous glucose infused. Following discontinuation of glucose infusion, endogenous glucose production was 3.9 +/- 0.3 mg X kg-1 X min-1, a value that was lower (P less than 0.05) than that observed in overnight-fasted normal children (6.3 +/- 0.3 mg X kg-1 X min-1) but not statistically different from the Ra of normal children fasted for 30 h (4.1 +/- 0.5 mg X kg-1 X min-1). Thus, children with GSD have glucose production rates that are 40% lower than those of normal children fasted overnight but equal to those of normal children fasted 30 h. Rates of glucose utilization during the 6 mg X kg-1 X min-1 glucose infusion were higher (0.05 less than P less than 0.1) than those of overnight-fasted normal children, despite lower plasma glucose concentrations when expressed on a body weight basis but not when expressed on the basis of estimated brain weight.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1984

Haemopoietic stem cells and the problem of self-renewal.

Haemopoiesis occurs in association with a complex stromal cell network in which all levels of haemopoietic cell development can be found. In order to understand the interaction between stromal cells and growth factors with the processes of self-renewal and differentiation, we have carried out a series of experiments attempting to define the circumstances in which self-renewal occurs in long-term marrow cultures. We have found that highly purified (FACS sorted) CFU-S do not undergo significant self-renewal in vitro when inoculated onto marrow stromal cells that can support self-renewal of unfractionated CFU-S. We have examined the effects of expression of the src oncogene on self-renewal of CFU-S. We have found that, following infection of long-term cultures with a retrovirus carrying the src oncogene, there is expression of src in certain of the stromal cells. There is also a selection for CFU-S that have an extended self-renewal capacity in vivo and in vitro. These CFU-S are non-leukaemic and can reconstitute haempoiesis in irradiated mice. Cells from src-infected cultures can also be induced to proliferate and form cell lines in vitro in the presence of interleukin 3 (IL-3). The cell lines produced are multipotential and non-leukaemic. From such data we conclude that expression of the src oncogene has (directly or indirectly) permanently altered the stem cells in such a way that they can undergo extensive self-renewal in situations that are unfavourable for growth and self-renewal of normal stem cells.

Animals↗