Search PubMed⌕ Search

Biomedical subjects

L C Paul

Publications and source records attributed to L C Paul.

At least 55 records · Page 3Linked to original sources
PubMed1997

alpha-smooth muscle actin and collagen deposition in dysfunctional renal transplants.

In normal kidneys, alpha-smooth muscle actin and collagen type III expression is restricted to vascular smooth muscle cells and perivascular fibrous tissues, respectively, but in pathological conditions their expression or deposition is more extensive. Using immunohistochemistry, we examined the expression of alpha-smooth muscle actin and type III collagen in 31 human renal transplant biopsy specimens obtained from patients with graft dysfunction. We found that dysfunctional renal transplants have increased alpha-smooth muscle actin and collagen III expression in the glomerulus and interstitium, but only glomerular alpha-smooth muscle actin expression correlates with graft function and prognosis.

Actins↗
PubMed1997

The marital context of end-stage renal disease: illness intrusiveness and perceived changes in family environment.

End-stage renal disease (ESRD) is associated with illness-induced disruptions (i.e. illness intrusiveness) that challenge patients and their families to accommodate and adapt. We advance previous research in ESRD by examining the extent to which illness intrusiveness extends to marital, non-marital, and family life among patients and their spouses. We also investigate whether gender and mode of renal replacement therapy moderate these effects. A sample of 19 ESRD patients and their spouses completed the Illness Intrusiveness Ratings Scale and the Family Environment Scale (FES) (completed with reference to two time frames, currently and before ESRD) in structured individual interviews. As hypothesized, ESRD patients reported significantly higher illness intrusiveness than their spouses, but this discrepancy was greater in relation to aspects of non-marital as compared to marital life. Significant moderating effects were observed for gender on the FES Relationship subscale and mode of renal replacement on the FES Personal Growth subscale. Spouses reported significantly more family emphasis on norms and the regulation of family members' behavior (FES System Maintenance) than patients. A pattern of significant correlations linked patient ratings of illness intrusiveness with both premorbid and current family environment. The pattern of findings is consistent with previous clinical reports that women and spouses are more likely than their male and patient counterparts to shoulder much of the burden of adapting family environment to accommodate life with ESRD and renal replacement therapy.

Adaptation, Psychological↗
PubMed1997

Psychosocial impact of illness intrusiveness moderated by self-concept and age in end-stage renal disease.

This study assesses whether a person's self-concept as a "chronic kidney patient" differentially moderates the psychosocial impact of illness intrusiveness--illness-induced lifestyle disruptions--across the life span. Renal transplant (n = 52) and maintenance dialysis patients (n = 49) completed the illness Intrusiveness Ratings Scale, a semantic-differential self-concept measure, and structured interviews measuring psychosocial well-being and emotional distress. Across ages, distress rose with increasing illness intrusiveness when self-concept was similar, but not dissimilar, to the chronic kidney patient stereotype. The relation between illness intrusiveness and psychosocial well-being differed significantly between younger and older respondents depending on whether they construed themselves as similar versus dissimilar to the chronic kidney patient. Although self-definition moderates the psychosocial impact of chronic disease, this varies across the life span and across affect states.

Adult↗
PubMed1996

Antihypertensive drug treatment in chronic renal allograft rejection in the rat. Effect on structure and function.

To gain insight into the contribution of immunologic and hemodynamic factors in the progressive demise of structure and function in chronic renal allograft dysfunction, we studied the histological changes, the immunostainable glomerular anionic sites, and glomerular capillary hydrostatic pressures of rat renal allografts with chronic rejection. Recipient animals were left untreated, received 8 weeks of treatment with the immunosuppressive drug cyclosporine, or received antihypertensive drugs consisting of the combination of reserpine, hydralazine and hydrochlorothiazide, the angiotensin-converting enzyme inhibitor cilazapril, or the angiotensin II receptor blocker L-158,809. Grafts in untreated recipients developed chronic interstitial inflammation, as well as vascular and glomerular lesions consistent with chronic rejection. These lesions were associated with immunohistochemical loss of the negatively charged heparan sulfate proteoglycan side chain. All treatment regimens decreased the systemic and glomerular capillary pressures and were associated with no loss of function, decreased proteinuria, and a tendency to improved graft function. Cyclosporine prevented all histological manifestations of rejection, and antihypertensive drugs decreased the extent of glomerular mesangiolysis and glomerulosclerosis; L-158,809 and cilazapril also inhibited graft atherosclerosis and tubular atrophy. We conclude that chronic rejection is primarily an immune-mediated process, but hemodynamic and angiotensin II-mediated effects may play a pivotal role in the expression of immune-mediated lesions.

Animals↗
PubMed1996

Smooth muscle cell migration into intima and adventitia during development of transplant vasculopathy.

Smooth muscle cell (SMC) migration from the medial layer into the intima is a characteristic feature of transplant vasculopathy and is thought to be regulated by locally produced cytokines. We studied the expression of smooth muscle alpha-actin, PDGF B-ligand and, PDGF alpha- and beta-receptors in rat aortic allografts with transplant vasculopathy using immunohistochemistry. At two weeks, an intense expression of PDGF B-ligand and, PDGF alpha- and beta-receptors was found in the neointima and adventitia. Medial SMC expression decreased with time in parallel with accumulation of smooth muscle alpha-actin in the neointima and adventitia. PDGF expression persisted in the adventitia. Prolonged ischemic storage time resulted in an increase in the number of alpha-actin-positive SMCs in the intima of syngeneic grafts. These data indicate that SMCs migrate into both the intima and adventitia. This migration may be induced, at least in part, by PDGF produced by graft invading monocyte-derived macrophages.

Actins↗
PubMed1996

Nitric oxide synthase inhibition is associated with decreased survival of cardiac allografts in the rat.

Nitric oxide is a biological mediator that regulates blood vessel wall tonus, enhances macrophage cytotoxicity, and inhibits cellular immune reactivity. Primary acute rejection is associated with increased intragraft production of NO but it is unknown whether this delays or enhances the loss of graft function. The aim of the current study was to determine the effect of L-NAME, a nitric oxide synthase inhibitor, on the course and histopathology of rat cardiac allografts with primary acute rejection. L-NAME decreased the graft survival time from 9.4+/-1.5 to 6.9+/-0.3 days; the histopathology at asystole showed predominantly ischemic necrosis. L-NAME combined with antihypertensive drugs restored the rejection time (from 8.6+/-0.4 to 14.2+/-3.2 days) and resulted in an acute rejection pattern. We conclude that blocking of nitric oxide formation during acute rejection of a vascularized cardiac graft results in a decreased graft survival time and ischemic graft necrosis, very likely secondary to unopposed vasoconstriction.

Animals↗
PubMed1996

Evidence for earlier stabilization of cyclosporine pharmacokinetics in de novo renal transplant patients receiving a microemulsion formulation.

Sequential cyclosporine pharmacokinetic assessments were performed at four centres within the context of a double-blind, multicenter clinical trial comparing the safety and tolerability of the conventional formulation with cyclosporine for microemulsion in de novo renal transplant patients. The initial average daily oral dose was 9.3 mg/kg given in two divided doses every 12 hr with subsequent dose reductions individually titrated to maintain trough concentrations within the target therapeutic range. Pharmacokinetic profiles were assessed at week 2, once between weeks 4-6, and at week 12 in 12 patients on the conventional formulation and 9 patients on the microemulsion. Over the study duration, cyclosporine daily doses were comparable in both study arms and were reduced in parallel from 9.2 to 6.9 to 4.7 mg/kg/day at the three successive pharmacokinetic visits. Dose-normalized peak and area-under-the-curve (AUC) increased between the week 2 and week 4-6 assessments for both formulations. Thereafter, these parameters continued to increase for the conventional formulation but exhibited a high degree of within-in patient stability for the microemulsion between week 4-6 and week 12. Between-formulation comparisons indicated that the rate and extent of cyclosporine absorption from the microemulsion were significantly higher over the study duration. Specifically, at week 2, 4-6 and 12, dose-normalized AUC was 49%, 63%, and 32% higher for the microemulsion. Intrasubject coefficients of variability for pharmacokinetic parameters of the conventional formulation ranged from 26.3% to 68.2%. Corresponding values for the microemulsion were reduced by approximately half, ranging from 13.1% to 38.7%. The correlation between predose trough concentration and AUC was stronger for the microemulsion (r(2)0.819 vs. 0.635) over the full range of systemic exposures attained throughout the study. These results provide initial evidence that, as doses are reduced with time posttransplant, the cyclosporine dose-exposure relationship from the microemulsion may stabilize earlier than that from the conventional formulation, allowing increased pharmacokinetic control over cyclosporine use in this critical posttransplant period.

Administration, Oral↗
PubMed1996

Anti-integrin (LFA-1, VLA-4, and Mac-1) antibody treatment and acute cardiac graft rejection in the rat.

Cell adhesion molecules mediate interactions with other cells and extracellular matrix, control cell infiltration in sites of inflammation, and regulate cell activation. Previous studies have shown that treatment of rat cardiac transplant recipients with a combination of antibodies against the T-cell integrins LFA-1 and VLA-4 gave a modest prolongation of graft survival. Current experiments were designed to examine the effect of blocking Mac-1, an important monocyte adhesion receptor and mediator of monocyte migration, together with anti-LFA-1 and anti-VLA-4 antibodies on cardiac graft survival and on the graft rejection pattern. The anti-Mac-1, CD11b-specific antibody OX-42 did not affect graft survival time although it did decrease the graft infiltration by rounded, ED-2-positive macrophages.

Acute Disease↗
PubMed1996

Growth factor transcripts in rat renal transplants.

Locally produced cytokines and growth factors may mediate tissue remodelling processes, as observed in renal transplants exposed to ischemia or acute rejection episodes. The present study was designed to investigate mRNA transcript levels of platelet-derived growth factor (PDGF)-receptor beta, PDGF-A, PDGF-B, fibroblast growth factor-1, and transforming growth factor beta 1 in normal rat kidneys, in kidneys following contralateral nephrectomy and in renal transplants with acute or chronic rejection. Platelet-derived growth factor-receptor beta mRNA levels increased significantly in syngeneic and allogeneic transplants in the first week after transplantation and in allogeneic transplants with chronic rejection. Immunohistochemistry showed induction of PDGF-receptor beta protein expression on vascular wall cells in such grafts. Platelet-derived growth factor-A chain mRNA levels increased in day 3 allografts and in syngeneic LEW grafts, while PDGF-B chain mRNA levels showed no significant changes with transplantation. Fibroblast growth factor-1 mRNA levels were detectable in normal kidneys, tended to decrease with acute rejection, and increased significantly in chronic rejection. Transforming growth factor-beta 1 transcripts increased in acute and chronic rejection; immunohistochemistry showed predominantly glomerular localization of the transforming growth factor-beta 1 protein. We conclude that transplantation and rejection are associated with changes in the intragraft mRNA levels for several growth factors; chronic rejection is characterized by an increase in fibroblast growth factor-1 and transforming growth factor-beta 1 transcript levels.

Animals↗