Search PubMed⌕ Search

Biomedical subjects

R J Powell

Publications and source records attributed to R J Powell.

At least 91 records · Page 5Linked to original sources
PubMed1997

Treatment of severe and difficult cases of systemic lupus erythematosus with tacrolimus. A report of three cases.

OBJECTIVES: An analysis of the efficacy of tacrolimus treatment in three patients with difficult and severe systemic lupus erythematosus (SLE) whose active disease had been previously poorly controlled by cyclosporine and cyclophosphamide. METHODS: A review of patient notes. RESULTS: Two patients are well controlled after six and nine months of treatment with tacrolimus 0.06 mg/kg/day and 0.18 mg/kg/day. Previous persistent vasculitis had resolved and other features of active disease were controlled. The third patient's vasculitis had not improved significantly after two months of treatment and tacrolimus 0.17 mg/kg/day was discontinued because of nephrotoxicity. CONCLUSION: Tacrolimus may be a useful additional immunosuppressive agent in some patients whose SLE is not well controlled by conventional treatments.

Adolescent↗
PubMed1997

Correlation between CD29 density on CD8+ lymphocytes and serum IgG in systemic lupus erythematosus.

The purpose of this paper is to establish whether there is increased lymphocyte adhesion molecule density in systemic lupus erythematosus (SLE), which could alter the migration pathways and activation thresholds of lymphocytes and thus contribute to the pathogenesis of the disease. We analysed the CD11a, CD29 and CD2 bound antibody molecule (bam) density on the CD4+ and CD8+ CAMhigh (primed) lymphocytes of 28 SLE patients (8 active and 20 inactive by BILAG), using reproducible flow cytometric measurements, standardized with fluorescent beads and antibodies of known fluorescein: protein ratios. In a second patient cohort (17 patients), we investigated whether CD29 density on CD8+ cells correlated with measures of humoral (serum IgG) or cellular (urine neopterin) activation. In the first cohort, 36% of patients had elevated CD29 (beta 1 integrin) density on CD8+ cells. In the second cohort, CD29 density on CD8+ cells was found to be closely associated with total plasma IgG (r = 0.71, P = 0.001), but not with urine neopterin, disease activity (BILAG) or drug treatment. We conclude that CD29 on CD8+ cells is associated with B cell activation in SLE.

Antigens, CD↗
PubMed1997

Clinical spectrum of familial Hibernian fever: a 14-year follow-up study of the index case and extended family.

OBJECTIVE: To determine the clinical spectrum and natural history of the disease "familial Hibernian fever" (FHF). DESIGN: We ascertained the disease status in all 54 living members and 9 deceased members of the extended family and conducted a detailed study of those affected. MATERIAL AND METHODS: All family members with FHF were clinically assessed and investigated fully, including human leukocyte antigen (HLA) typing. Medical records were studied for relevant clinical features, drug therapy, and complications. All previously obtained histologic specimens were reviewed. Three typical case histories are presented. RESULTS: The updated family tree confirmed an autosomal dominant mode of inheritance in 16 living members with FHF. In addition to the febrile attacks, abdominal pain and localized myalgias were almost invariably present. Episodic erythematous patches, conjunctivitis, and unilateral periorbital edema were also notable features. Of 10 affected male family members, 8 had inguinal hernias (in comparison with 1 of 21 unaffected male family members). No association with HLA status was noted. Secondary amyloidosis was found in one affected member. CONCLUSION: The characteristic clinical features and natural history of FHF distinguish it from other periodic fever syndromes. The discovery of amyloidosis related to FHF alters the prognosis associated with this condition and emphasizes the need to search for effective treatment strategies. The high prevalence of inguinal herniation may provide clues about its pathogenesis.

Adult↗
PubMed1997

Oral bacterial vaccine vectors for the delivery of subunit and nucleic acid vaccines to the organized lymphoid tissue of the intestine.

Bacterial vaccine vectors have the potential to deliver a number of antigens from bacterial, protozoan and viral pathogens. To further develop the utility of bacterial vaccine vectors we are currently evaluating three model systems: 1. A Salmonella-ETEC Vaccine Vector; 2. A Salmonella-HIV Vaccine Vector, and 3. Novel Live Bacterial Nucleic Acid Vaccine Vectors. Through our studies, and those of others, significant progress has been made toward bacterial vaccine vector systems that effectively deliver subunit and nucleic acid vaccines to the organized lymphoid tissue of the intestine. The practical reality of these findings is discussed.

AIDS Vaccines↗
PubMed1996

Optimization of live oral Salmonella-HIV-1 vaccine vectors for the induction of HIV-specific mucosal and systemic immune responses.

Recent evidence suggests that live oral Salmonella-HIV vaccine vectors have the potential to elicit HIV-specific T cell-mediated immunity in both the mucosal and systemic compartments. We are using the mouse-typhoid model to identify Salmonella::HIV vaccine vector constructs that elicit HIV-specific mucosal and systemic immune responses. Oral immunization of mice with a Salmonella strain that expresses recombinant gp120 (rgp120) in the cytoplasm of the vector elicits a modest gp120-specific T cell proliferation response in the spleen. However, such Salmonella constructs did not stimulate the development of gp120-specific serum IgG or cytotoxic T lymphocytes (CTLs). Interestingly, the majority of cytoplasmically-expressed rgp120 forms inclusion bodies in Salmonella. We believe that in this form rgp120 is highly susceptible to protease degradation by the vector. As such, cytoplasmic rgp120 may not persist in the host after vaccination, resulting in the modest immunogenicity of rgp120 in these constructs. To circumvent this problem we constructed Salmonella strains that express rgp120 on the surface of the vector. Preliminary data suggest that surface-expressed rgp120 is significantly more immunogenic in both the mucosal and systemic compartments than cytoplasmic rgp120. These results, therefore, support the proposal that Salmonella vectors will be a safe and inexpensive means for delivery of HIV antigens to, and the elicitation of HIV-specific T cells in, the mucosal and systemic compartments.

Administration, Oral↗
PubMed1996

Effect of aprotinin on smooth muscle cell proliferation, migration, and extracellular matrix synthesis.

Aprotinin (AP) is a plasmin inhibitor commonly used to limit bleeding during reoperative coronary bypass surgery. The effect on smooth muscle cell (SMC) behavior and the development of intimal hyperplasia has not been evaluated. This study examines the effect of AP on SMC proliferation, migration, and extracellular matrix synthesis. Bovine aortic SMCs (three to five passages) plated at 5 x 10(4) cells/ml were treated with 1.0, 10, 100, and 1000 microg/ml AP. Proliferation was measured as micrograms of DNA per well, after 3 days in culture. SMC migration was measured after treatment with mitomycin C (20 microg/ml, to study migration in the absence of proliferation) by means of a fence assay. Extracellular matrix was quantitated utilizing a tritiated proline assay and corrected for cell density (cpm/microg DNA). Data are presented as means +/- SEM; ANOVA and post hoc Tuckey test were used to test for significant differences. AP stimulated SMC proliferation at dosages of 100 microg/ml (353 +/- 6 microg DNA, SMC control vs 440 +/- 11, 100 microg/ml; P < 0.05) and 1000 microg/ml (353 +/- 6, SMC control vs 503 +/- 14, 1000 microg/ml; P < 0.01). AP concentrations less than 100 microg/ml had no effect on SMC proliferation. A dose-response relationship existed between AP and SMC migration. AP doses as low as 10 microg/ml increased SMC migration from 66 +/- 4 mm2 (control SMC) to 90 +/- 4 mm2 (P < 0.02) while the maximal dose of AP (1000 microg/ml) produced an almost twofold increase in migration (66 +/- 4, SMC control vs 113 +/- 3, 1000 microg/ml group; P < 0.0001). AP had no effect on extracellular matrix synthesis. AP stimulated vascular SMC migration and proliferation but not matrix synthesis in vitro. These data suggest that AP could augment the development of intimal hyperplasia following bypass surgery.

Animals↗
PubMed1996

Endothelial cell modulation of smooth muscle cell morphology and organizational growth pattern.

Intimal hyperplasia is characterized by smooth muscle cell (SMC) dedifferentiation from a contractile to a synthetic phenotype prior to migration and proliferation. Regulatory mechanisms controlling SMC phenotype are not well known. This study examined the effect of endothelial cells (ECs) on SMC morphology in coculture. Subcultured bovine ECs and SMCs were plated on opposite sides of a 13 microns thick, semipermeable membrane (0.45 micron pores, Cyclopore) to allow potential humoral and cellular cross-membrane communication. SMCs were studied (5 wells/group) in coculture opposite confluent ECs (EC/SMC) and alone (SMC controls). After 4 days of culture in Dulbecco's modified Eagle medium/2.5% calf serum, SMCs were harvested. The ratio of protein/DNA was measured as an index of SMC hypertrophy (synthetic SMC phenotype). SMCs were examined with light and scanning electron microscopy to evaluate cell surface area, cellular morphology, and macroscopic growth characteristics. Flow cytometry was used to determine the cellular RNA/DNA ratio. SMC control cultures had a significantly greater protein-to-DNA content than SMCs cocultured with ECs (175 +/- 9 vs. 115 +/- 7 micrograms protein/micrograms DNA; p < 0.001). SMC control cultures also had 6.5 times greater cell surface area (5.8 +/- 0.3 x 10(3) microns2) than cocultured SMCs (0.9 +/- 0.1; p < 0.001). In SMC control cultures, SMC hypertrophy and rapid "hill and valley" formation were observed. In contrast, SMCs from the EC/SMC group exhibited a more spindle-shaped, contractile-appearing phenotype with more uniform, evenly distributed cells and no hill and valley formation. SMC control cultures also had a higher RNA/DNA ratio. Thus the presence of confluent ECs substantially altered the morphology and growth characteristic normally observed for SMCs in vitro. This coculture system provides a model to further study EC-SMC interaction, which could have important in vivo consequences.

Animals↗
PubMed1996

Matrix-specific effect of endothelial control of smooth muscle cell migration.

PURPOSE: Smooth muscle cell (SMC) migration is a critical element in the development of intimal hyperplasia. The effect of endothelial cells (ECs) on SMC migration and the modulation of this cell-to-cell interaction by extracellular matrix is not well understood. METHODS: To examine this relationship SMCs and ECs were cocultured on opposite sides of a semipermeable membrane and were compared with SMCs cultured alone. To assess migration SMCs were plated at confluent density into the center of the membrane with a steel fence. After the fence was removed, SMCs were treated for 2 hours with mitomycin C (20 micrograms/ml) to assess migration independent of proliferation. Cell migration was measured with morphometry. Experiments were performed on plastic and membranes coated with fibronectin or type I collagen (n > or = 8/group). Cell adhesiveness was quantitated by cell attachment and spreading assays. RESULTS: ECs stimulated SMC migration by 187% when compared with SMCs cultured alone on plastic and by 160% when cultured on fibronectin (p < 0.01). Type I collagen stimulated migration of SMCs cultured alone and prevented EC stimulated migration in cocultured SMCs (p < 0.01). Cell adhesiveness was significantly increased in cocultured SMCs compared with SMCs cultured alone regardless of whether cells were cultured on plastic (EC/SMC, 13.5 +/- 0.6 SMCs/high power field vs SMC, 8.9 +/- 0.5, p < 0.01), fibronectin (16.3 +/- 0.8 vs 12.3 +/- 0.7, p < 0.01) or type I collagen (15.5 +/- 1.0 vs 12.4 +/- 0.6, p < 0.01). ECs increased SMC cell spreading on plastic and fibronectin when compared with SMCs cultured alone. No difference in SMC cell spreading was seen in the presence or absence of ECs when cells were cultured on type I collagen. EC-SMC contact was not required; EC-conditioned media alone increased SMC migration by 75% when compared with SMCs cultured alone. Our data suggest that ECs increase SMC migration by a diffusable molecule that may also alter SMC adhesion molecule expression. Extracellular matrix composition can attenuate these effects.

Animals↗
PubMed1996

Peripheral blood lymphocyte adhesion molecule deployment in the immune response.

Using precise and reproducible flow cytometric measurements, the surface densities of the cell adhesion molecules (CAMs) CD29, CD2 and CD11a were studied on the CAMhigh (primed) subsets of peripheral blood CD4+ and CD8+ lymphocytes in 56 healthy subjects; 18 patients with acute bacterial infections, 19 with acute viral infections and 18 with chronic inflammatory conditions. By Mann-Whitney analysis, with significant P values adjusted for multiple comparisons to less than 0.0007, patients with viral infections were found to have increased CD11a on CAMhigh cells (an increase in median values of 13.7% for CD4+ lymphocytes and 15.8% for CD8+ lymphocytes); patients with chronic conditions have increased CD29 on CD8+CAMhigh lymphocytes (an increase in the median of 19%); and patients with bacterial infections have increased CD2 on CD8+CAMhigh cells (an increase in the median of 8%). There were marked individual increases in CD29 density: eight (15%) patients had CD29 gender-adjusted density on CD4+ cells greater than the control mean + 3 standard deviations (SD). CD29 densities on CD8+ cells were elevated to greater than control mean + 3 SD in 12 (22%) patients. By multiple regression analysis CD11a density on CD8+ and CD4+ cells and CD2 density on CD4+ cells were found to be associated with HLA-DR expression, but not with CD25 expression. Using standardized intercepts the authors demonstrated that there are very few circulating CDllahighCD25+ cells, suggesting that these are rapidly extravasated. This study demonstrates that in disease, lymphocyte adhesion molecules are not deployed in concert and there are characteristic deployment patterns for different types of immune response.

Acute Disease↗
PubMed1996

Incidence of ovarian failure in systemic lupus erythematosus after treatment with pulse cyclophosphamide.

OBJECTIVE: To investigate the incidence of ovarian failure after pulse cyclophosphamide treatment in systemic lupus erythematosus (SLE) and to compare this with two control groups: SLE patients treated with azathioprine, and a healthy age matched population. METHODS: All women patients with SLE treated with pulse cyclophosphamide in our department were identified and questioned concerning menstrual history. All the hospital notes were reviewed and details recorded on dose of cyclophosphamide, duration of treatment, side effects and lowest pretreatment neutrophil and leucocyte counts during the course of treatment. Disease controls were recruited from our department and healthy controls from the local family health services authority (FHSA) register. RESULTS: Incidence of ovarian failure in the premenopausal cyclophosphamide treated group was 54% and the incidence of premature menopause (occurring before age 40 years) was 41%. Increasing age at start of treatment showed a linear trend with incidence of ovarian failure (p = 0.01). Using logistic regression, increasing duration of treatment was related to incidence of ovarian failure (p = 0.047 in those treated age 35 years or younger). An association between the lowest neutrophil count throughout the treatment period, when taken immediately before each planned cyclophosphamide pulse, and the incidence of ovarian failure was also demonstrated (p = 0.04 in those treated before age 40 years). CONCLUSION: Ovarian failure--in particular, premature failure after treatment with pulse cyclophosphamide--is common. Factors associated with increased risk include greater age at start of treatment, longer period of treatment, and greater degree of marrow suppression as assessed by the neutrophil count immediately before each planned cyclophosphamide pulse.

Adolescent↗