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Biomedical subjects

E Eng

Publications and source records attributed to E Eng.

At least 37 records · Page 2Linked to original sources
PubMed1995

Cellular proliferation and macrophage influx precede interstitial fibrosis in cyclosporine nephrotoxicity.

Chronic cyclosporine (CsA) nephrotoxicity is a major complication of solid organ transplantation, and is characterized histologically by striped tubulointerstitial fibrosis, tubular atrophy, and hyalinization of the afferent arteriole, a highly specific finding in cyclosporine injury. The salt-depleted rat model of chronic cyclosporine nephropathy mimics these lesions in humans. We conducted sequential studies of this model in groups of pair fed rats (N = 6) treated with CsA (15 mg/kg, s.q.) or an equivalent dose of olive oil. Proliferation of tubular and interstitial cells was documented early in the medulla by day 5 (3.2 +/- 2.1 vs. 0.81 +/- 0.4 cells/HPF in CsA vs. control, P < 0.02), and was maximal in areas of interstitial fibrosis by day 35 (7.9 +/- 3.7 vs. 0.52 +/- 0.2 cells/HPF in CsA vs. control, P < 0.005). The interstitial fibrosis was associated with a significant macrophage influx by day 35 (13.9 +/- 3.5 vs. 1.5 +/- 0.32 cells/HPF, CsA vs. control, P < 0.005), which correlated with increased cortical tubular staining for the macrophage adhesion protein, osteopontin. Elevated serum creatinine correlated with interstitial fibrosis at day 35 (0.85 +/- 0.11 vs. 0.40 +/- 0.03 mg/dl Cr, CsA vs. control, P < 0.005) by linear regression (r = 0.9, P < 0.05). Medullary proliferation and interstitial fibrosis correlated with decreased tubular concentrating ability, and higher urinary volume. Cortical interstitial fibrosis was maximal at day 35 and was associated with an increase in type I and type IV collagen deposition, while tubular injury was associated with increased vimentin expression. Tubular interstitial cells also expressed increased vimentin early in the medulla (day 10) and later in the cortex. Both groups remained normotensive despite significantly elevated juxtaglomerular (JG) apparatus renin expression in CsA treated animals, implicating the intrarenal-renal renin-angiotensin system in this disease. We conclude that cyclosporine nephrotoxicity is associated with early tubular and interstitial cell proliferation, and a significant macrophage influx that precedes the development of cortical interstitial fibrosis and afferent arteriolar hyalinosis. These early cellular changes correlate with functional abnormalities including decreased creatinine clearance (CCr) and decreased medullary concentrating ability, which stabilized despite progressive fibrosis. These cellular events may be important in the pathogenesis of chronic CsA nephrotoxicity.

Animals↗
PubMed1995

Modulation of experimental mesangial proliferative nephritis by interferon-gamma.

The observation that interferon-gamma (IFN-gamma) inhibits cell proliferation and collagen synthesis of a variety of cell types in culture has suggested that IFN-gamma may be useful in the treatment of fibroproliferative diseases. We administered recombinant IFN-gamma subcutaneously (10(5) U/kg/day for 3 days) to rats, beginning one day after the induction of mesangial proliferative nephritis with anti-Thy 1 antibody. IFN-gamma reduced glomerular (primarily mesangial) cell proliferation by 44% at days 2 and 4 compared to vehicle injected control rats with anti-Thy 1 nephritis (that is, proliferating cells that excluded the macrophage marker, ED-1, P < 0.001). Despite the inhibition of mesangial cell proliferation, IFN-gamma did not reduce the overall extracellular matrix deposition (by silver stain) or deposition of type IV collagen or laminin (by immunostaining) at 4 or 7 days, and glomerular type IV collagen and laminin mRNA levels were increased (1.4 and 1.7-fold) at 4 days relative to controls. The inability of IFN-gamma treatment to reduce mesangial matrix expansion may relate to the fact that IFN-gamma treated rats had a twofold increase in glomerular macrophages (that is, ED-1 positive cells, P < 0.001 at 2 and 4 days) with an increase in oxidant producing cells (day 2, P < 0.05) and a 1.6-fold increase in glomerular TGF-beta mRNA expression (4 days). This suggests that the effect of IFN-gamma to inhibit mesangial cell proliferation in glomerulonephritis may be offset by the ability of IFN-gamma to increase glomerular macrophages and TGF-beta expression. These data also show that IFN-gamma can partly dissociate the mesangial proliferative response from the extracellular matrix expansion in glomerulonephritis.

Animals↗
PubMed1995

Strengthening individual and community capacity to prevent disease and promote health: in search of relevant theories and principles.

The dominant theoretical models used in health education today are based in social psychology. While these theories have increasingly acknowledged the role of larger social and cultural influences in health behavior, they have many limitations. Theories seek to explain the causes of health problems, whereas principles of practice, which are derived from practical experience, assist intervenors to achieve their objectives. By elucidating the relationships between theory and practice principles, it may be possible to develop more coherent and effective interventions. The key research agenda for health education is to link theories at different levels of analysis and to create theory-driven models that can be used to plan more effective interventions in the complex environments in which health educators work.

Community Health Services↗
PubMed1994

Renal proliferative and phenotypic changes in rats with two-kidney, one-clip Goldblatt hypertension.

Angiotensin II (AII) is a vasoconstrictive peptide with hypertrophic and mitogenic effects on many cell types. Previous studies have shown that in vivo administration of AII in rats results in proliferation of, and phenotypic changes in, many renal cell populations, but in doses also causing hypertension. Thus, it was not possible to differentiate nonhemodynamic from hypertensive effects of AII. Therefore, we studied rats with renin-dependent, AII-mediated hypertension (the two-kidney, one-clip Goldblatt model; mean systolic blood pressure 238 +/- 48 v 140 +/- 6 mm Hg in sham-operated controls). The unclipped kidneys, which were exposed to high blood pressure, developed significant glomerular and tubulointerstitial injury, tubulointerstitial cell proliferation, dense focal interstitial monocyte-macrophage influx, increased deposition of types I and IV collagen, as well as increased cellular expression of desmin and actin, in tubulointerstitial areas when examined at 11 weeks. In contrast, clipped kidneys, protected from hypertension but with high local renin expression, had minimal abnormalities. These studies suggest that in this model increased renin, and presumably AII, does not mediate significant proliferative or phenotypic changes in the kidney in the absence of hypertension at 11 weeks.

Angiotensin II↗
PubMed1994

Measuring community competence in the Mississippi Delta: the interface between program evaluation and empowerment.

If political dynamics are included in the definition of community, health promotion programs have a greater potential to recognize that assisting people to empower their communities is as important as assisting them to improve their health. This paper reports on the evaluation methods employed for a health promotion program in a rural poor county of the Mississippi Delta that chose to define community in this way. The evaluation took an action research approach so that the methods would not contradict or interfere with the program's empowerment agenda. The methods required a close and collaborative working relationship among evaluators and local service providers, community leaders, and program staff who defined and operationalized eight dimensions of community competence, determined the units of analysis, and developed the data collection protocol. Emphasis was placed on using the data to engage the program and three communities in a dialogue on how to confront a system with the difficult issues they faced. The findings revealed that after 1 year of implementation, community competence moved from social interactions internal to communities to those more externally focused on mediating with outside institutions and officials. At the same time, measures of self-other awareness and conflict containment showed a decrease or virtual nonexistence.

Adolescent↗
PubMed1993

The Save our Sisters Project. A social network strategy for reaching rural black women.

Why are older black women screened less for breast cancer? What can be done to narrow the racial gap in mammography screening? These are the questions addressed by the Save Our Sisters (SOS) Project, a pilot demonstration study funded by the National Cancer Institute in a rural county of North Carolina. The target population is 2600 black women 50-74 years of age residing in the county. To assist these women to obtain annual mammograms, SOS has recruited and trained 64 black women who are "natural helpers" to serve as lay health advisors. The lay health advisors reach older black women through their existing kin, friendship, and job networks. Responses from 14 focus group interviews found that when it is a matter of older black women's health concerns, women turn to certain women for social support. Responses revealed factors related to the individual woman and her social network that influence rural black women's seeking breast cancer screening. These results were applied to the Social Change model for designing the training and three network intervention strategies: (1) providing social support (information and referrals, emotional caring, and tangible assistance) through interpersonal counseling with women in their social networks; (2) working as a group, planning and implementing breast cancer control and prevention activities through community-based organizations to which advisors belong (e.g., church groups, civic groups, and social groups); and (3) establishing themselves as a non-profit, community-based SOS Association to sustain project interventions after the funding period. The SOS Community Advisory Group and the advisors developed innovative methods of recruitment, implementation, and follow-up. The community programs they have initiated are: (1) the Adopt-A-Sister Program, which assists black women who cannot afford the cost of a mammogram; (2) a committee on understanding the health care system, which assists women in negotiating regulations and using health care providers; (3) a training committee, which recruits and trains additional advisors; (4) a support group for black women with diagnoses of breast cancer; and (5) a speakers bureau, which has produced a 10-minute video, brochure, and tee-shirts as community education materials.

Black or African American↗
PubMed1993

Heparin suppresses mesangial cell proliferation and matrix expansion in experimental mesangioproliferative glomerulonephritis.

Proliferation and extracellular matrix (ECM) overproduction by glomerular mesangial cells characterizes many types of glomerulonephritis and often precedes the development of glomerulosclerosis. Heparin is a potent inhibitor of mesangial cell growth in vitro. We examined whether standard heparin can inhibit mesangial cell proliferation in vivo in the mesangioproliferative anti-Thy 1.1 nephritis. Untreated control rats were compared to rats infused with heparin either early (day -2 to 1) or late (day 2 to 5) after induction of anti-Thy 1.1 nephritis. The results show that heparin treatment significantly reduced mesangial cell proliferation regardless of when it was initiated. Heparin (either early or late treatment) also reduced mesangial basic fibroblast growth factor (bFGF) expression and platelet-derived growth factor (PDGF) receptor up-regulation as reflected by immunostaining, whereas PDGF B-chain expression was reduced only by late heparin treatment. Furthermore, heparin treatment markedly inhibited the mesangial matrix expansion for a variety of ECM proteins, including laminin, type I and IV collagen, fibronectin and entactin. Heparin did not affect the initial mesangiolysis, glomerular macrophage influx, deposition of anti-Thy 1.1 IgG or fibrinogen, or the glomerular platelet influx. These results suggest that heparin, via its antiproliferative rather than anticoagulant effect, can inhibit mesangial cell proliferation, overexpression of polypeptide growth factors, and ECM protein overproduction in vivo. The beneficial effect of heparin can be demonstrated even if treatment is initiated after the development of nephritis. By virtue of these properties, heparin may be an effective agent in the treatment of human mesangioproliferative disease and in the prevention of glomerulosclerosis.

Animals↗
PubMed1993

Infusion of platelet-derived growth factor or basic fibroblast growth factor induces selective glomerular mesangial cell proliferation and matrix accumulation in rats.

Mesangial cell (MC) proliferation and extracellular matrix expansion are involved in the pathogenesis of glomerulosclerosis and renal failure. In vitro, PDGF and basic fibroblast growth factor (bFGF) regulate MC proliferation and/or matrix production. To elucidate the role of PDGF and bFGF in vivo, equimolar concentrations of recombinant PDGF-BB or bFGF or vehicle were infused intravenously into rats over a 7-d period. Rats were either nonmanipulated ("normals") or had received a subnephritogenic dose of anti-MC antibody ("anti-Thy 1.1 rats") before the infusion period. Glomerular cell proliferation (anti-proliferating cell nuclear antigen immunostaining) on days 2, 4, and 7 was unchanged in vehicle-infused normals or anti-Thy 1.1 rats. PDGF infusion increased glomerular cell proliferation 32-fold in anti-Thy 1.1 rats and an 11-fold in normals on day 2. bFGF increased glomerular cell proliferation fourfold in anti-Thy 1.1 rats but was ineffective in normals. Induction of cell proliferation in all kidneys was limited to the glomerulus. The majority of proliferating cells were identified as MC by double immunolabeling. No significant proteinuria, glomerular leukocyte, or platelet influx developed in any group. Glomerular matrix expansion with increased deposition of type IV collagen, laminin, and fibronectin, as well as upregulated laminin and collagen IV mRNA expression was confined to PDGF-infused anti-Thy 1.1 rats. These results show that PDGF and, to a lesser degree, bFGF are selective MC mitogens in vivo and that previous subclinical injury can enhance this MC response. The data thereby support a role of these cytokines in the pathogenesis of glomerulosclerosis.

Animals↗
PubMed1993

Factors involved in the regulation of mesangial cell proliferation in vitro and in vivo.

One of the central features of many human glomerular diseases is the proliferation of the smooth muscle cell-like mesangial cells. While a multitude of mitogens for mesangial cells has been proposed on the basis of in vitro experiments, the factors involved in the regulation of mesangial cell proliferation in vivo remain largely undefined. To investigate the regulation of mesangial cell proliferation in vivo we have studied the mesangioproliferative glomerulonephritis that is induced by injection of antibody directed against the Thy 1.1 antigen on the mesangial cell surface in rats. In this review, we discuss the role of three cytokines in the mesangioproliferative response, namely platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta (TGF-beta). All three cytokines are present in various inflammatory cells as well as in mesangial cells themselves, thereby allowing these factors to exert both paracrine and autocrine regulatory functions on mesangial cells. In vivo studies show that PDGF, bFGF and TGF-beta participate in either the mesangial cell proliferation or the mesangial matrix expansion that follows mesangial cell injury with anti-Thy 1.1 antibody. Based on currently available data we propose that bFGF may participate in the initiation, PDGF in the maintenance, and TGF-beta in the resolution of mesangial cell proliferation in vivo. Further analysis of the mitogens operative in vivo may ultimately result in the design of new therapeutic strategies to treat progressive glomerular mesangioproliferative diseases.

Animals↗
PubMed1992

Rat glomerular mesangial cells synthesize basic fibroblast growth factor. Release, upregulated synthesis, and mitogenicity in mesangial proliferative glomerulonephritis.

Mesangial injury and cell proliferation are frequent findings in various glomerular diseases in man. Previous studies have demonstrated that basic fibroblast growth factor (bFGF) is a potent mesangial cell mitogen in vitro. To further elucidate the role of bFGF in rat mesangial cell (RMC) proliferation, we examined whether RMC synthesize bFGF in vitro and whether bFGF is involved in mesangial proliferation in vivo. Cultured RMC expressed bFGF protein (23, 21.5, and 18 kD forms) and bFGF mRNA, and released biologically active bFGF into the culture medium after antibody- and complement-mediated injury. Normal rat glomeruli in vivo contained no detectable bFGF mRNA, but bFGF protein (23 and 21.5 kD) could be demonstrated, which immunolocalized to the mesangium. Glomerular bFGF decreased markedly during the acute phase of glomerulonephritis induced by anti-Thy 1.1 antibody, compatible with mesangial bFGF release after complement-mediated mesangiolysis. During the subsequent mesangial proliferative phase, glomerular bFGF protein and mRNA increased above normal. Intrarenal infusion of heparin did not affect the bFGF immunostaining of glomeruli at this stage, indicating a predominantly intracellular localization of the bFGF. The capability of bFGF to mediate proliferation in the anti-Thy 1.1 model was further supported by experiments in which intravenous bFGF given 24 h after a subnephritogenic dose of anti-Thy 1.1 antibody led to a 4.9- to 5.1-fold increase in glomerular cell proliferation (with > 60% of the cells identified as mesangial cells by double immunolabeling). No such increase was observed in normal rats injected with bFGF. These data show that mesangial cells produce and release bFGF after injury and that bFGF is mitogenic for injured mesangial cells in vivo. Release of mesangial cell bFGF thus may be an important mechanism involved in the initiation of mesangial cell proliferation in vivo.

Animals↗
PubMed1991

Injuries among medical laboratory housekeeping staff: incidence and worker perceptions.

Housekeepers' injury experiences in medical laboratories have not been reported previously. Review of injury incident reports for housekeepers assigned to medical research laboratories in a major university revealed an incidence rate of 46 injuries per 100 housekeepers per year from 1985 to 1988. Thirty-seven percent of the injuries were cuts and punctures, with 70% of these attributable to glass, needles, or cutting instruments. In a survey, 65% of housekeepers indicated that they do not always report their injuries, but the injury pattern they described paralleled those recorded in incident reports. Housekeepers identified behavioral and environmental factors that can contribute to laboratory injuries, including: lack of knowledge; failure to use protective equipment; carelessness; and, "sharps" (ie, sharp needles or glass) in the trash.

Accidents, Occupational↗
PubMed1991

The acceptability of childhood immunization to Togolese mothers: a sociobehavioral perspective.

A study was conducted in Togo to investigate the lack of acceptance of childhood immunization from a social science perspective. In each village focus group interviews were conducted with approximately 12 mothers to discuss their beliefs and knowledge, social and cultural norms and practices, and experiences with health services that hinder or promote the acceptability of childhood immunization. The problem of failure to complete the immunization series was explained in terms of mothers' lack of knowledge of when to return or their forgetfulness rather than inadequate knowledge about the importance of returning. Other barriers included the requirement to keep and present a vaccination card, waiting time at the clinic, lack of information about available services, and laziness. Rather than endorsing strategies that target individuals, mothers suggested increasing the level of social control exerted by decision makers in their communities (the village chief could direct the town crier to announce the passing of each week to help parents keep track of time between immunizations) and increasing the level of social support by having a meeting to support the importance of completing the vaccination series and to organize mothers who go to the clinic to inform others in their neighborhoods about vaccination.

Costs and Cost Analysis↗