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Biomedical subjects

D A Power

Publications and source records attributed to D A Power.

105 records · Page 6Linked to original sources
PubMed1983

B lymphocyte antibodies associated with successful renal transplantation and successful pregnancy.

This study shows that non-cytotoxic Fc receptor blocking antibodies occurred more frequently in pre-transplant sera when the recipient had been transfused over five units of blood. Moreover 7/12 previously untransfused patients developed Fc receptor blocking antibodies during an elective blood transfusion regime. Erythrocyte antibody-rosette-inhibiting antibodies were also found at significantly higher values in the sera of women during the first trimester of a normal first pregnancy than in women studied at the time of spontaneous abortion. Family studies showed that this activity was linked to the HLA gene complex. These results indicate that EA inhibiting antibodies directed against MHC linked antigens are associated with specific abrogation of the immune response.

Abortion, Habitual↗
PubMed1983

Acute renal failure due to continuous rifampicin.

We describe the clinical and pathological features of acute renal failure which occurred in a patient receiving a first course of antituberculous therapy, including daily rifampicin. Renal biopsy specimens demonstrated an interstitial nephritis. The renal lesion resolved three weeks after the cessation of rifampicin, as evidenced by improvement in renal function and the return of nuclear magnetic resonance tomographic studies to normal. This is only the fifth reported instance of renal impairment following continuous rifampicin therapy, despite widespread use of the drug in a daily dose. The possible toxic interaction of rifampicin and antituberculous drugs which are excreted predominantly by the kidneys is also described.

Acute Kidney Injury↗
PubMed1982

Possible mechanism of action of transfusion effect in renal transplantation.

The mechanism by which blood transfusions given before renal transplantation improves allograft survival was studied in 31 transplant recipients. The presence of non-cytotoxic, Fc receptor blocking antibodies to donor and leukaemic B lymphocytes in pre-transplant sera correlated with both improved graft survival (p less than 0.03 and less than 0.1, respectively) and the number of blood transfusions given (p less than 0.05 and less than 0.03, respectively). Moreover, 6 out of 10 previously untransfused prospective transplant recipients developed these potentially protective antibodies during a course of elective blood transfusions. These results indicate that such non-cytotoxic, Fc receptor blocking antibodies in pretransplant recipient sera (a) are associated with improved allograft survival, (b) correlate with the number of blood transfusions given, and (c) can develop in response to blood transfusion.

B-Lymphocytes↗
PubMed1982

Nuclear magnetic resonance tomographic imaging in renal disease.

The non-invasive diagnostic technique of whole body nuclear magnetic resonance (NMR) imaging was evaluated in 60 patients. 30 of these patients were known to have various renal diseases and the remainder had normal renal function. In the demonstration of space-occupying lesions of the kidney, NMR proved to be as diagnostically accurate as ultrasound and intravenous urography; it was, moreover, as specific as ultrasound in differentiating malignant tumours from benign cystic lesions. The specificity of NMR was superior to both ultrasound and IVU in the diagnosis of parenchymal disease in normally situated kidneys and in renal transplants. Hydronephrotic kidneys were readily demonstrated.

Graft Rejection↗
PubMedDate not supplied

Posture-related tachycardia in older patients with hyponatremia.

Hyponatremia (HN) is the commonest electrolyte abnormality in elderly patients. Its etiology in this setting is poorly understood. In this study, the authors aim to compare the hemodynamic and hormonal responses of a group of older patients with a predisposition to HN with a group of age-matched controls. We assessed hemodynamic and hormonal responses to postural challenge in 15 patients over age 65 with serum sodium concentrations of less than 130 mM (mean 128.7 mM) and 15 age-matched controls with normal sodium concentrations. Patients remained recumbent for 1 h and stood for the second. Blood was drawn at baseline and at 15 min intervals. Blood pressure (BP) and pulse rates (PR) were monitored electronically. Plasma arginine vasopressin (AVP), atrial natriuretic peptide (ANP), renin and aldosterone were determined periodically during the study period. No difference in BP between groups was noted. PR increased significantly in the HN group only within 3 min of standing (from 71 +/- 4 to 86 +/- 5, P<0.01) and remained significantly higher than controls until 90 min (87 +/- 5 vs. 69 +/- 4, P<0.01). While plasma AVP levels increased significantly following 30 min standing and remained elevated for both HN and control groups, it did not differ significantly between the two. Baseline plasma ANP levels were significantly higher in HN patients compared with controls and remained significantly higher (P<0.05) throughout the study. There was no significant difference in plasma renin or aldosterone levels between groups during the study period. We have demonstrated differing autonomic and hormonal responses to orthostatic challenge between HN patients and age-matched controls. Water retention due to the syndrome of inappropriate anti-diuretic hormone secretion (with reset osmostat) may lead to raised ANP levels in this older cohort of patients. Further physiological studies are required to clarify the precise mechanism of these varying responses.

Journal Article↗
PubMedDate not supplied

Inhibition with antisense oligonucleotide suggests that IkappaB-alpha does not form a negative autoregulatory loop for NF-kappaB in mesangial cells.

The IkappaB proteins are important in the regulation of the NF-kappaB/Rel group of transcription factors which are pivotal in the inflammatory response. IkappaB-alpha is itself upregulated by activation of NF-kappaB and is postulated to be part of a negative feedback loop. This role of IkappaB-alpha has been challenged, however, by recent evidence that demonstrates (1) continued activation of NF-kappaB in mesangial and endothelial cells despite the resynthesis of IkappaB-alpha protein and (2) that inhibition of the transactivating activity of NF-kappaB by corticosteroids can be dissociated from a rise in IkappaB-alpha protein. We investigated the role of IkappaB-alpha in mesangial cells using a phosphorothioate antisense oligonucleotide directed against the translational start point of IkappaB-alpha. If IkappaB-alpha does function as a negative feedback inhibitor in these cells, then reducing IkappaB-alpha levels should lead to an increase in NF-kappaB activity. We first demonstrated that IkappaB-alpha protein resynthesis following stimulation could be specifically reduced. We then showed that NF-kappaB DNA binding was not increased with antisense treatment following stimulation. Finally, NF- kappaB-dependent gene signalling after stimulation (determined through an NF-kappaB luciferase reporter and upregulation of the mRNA of known NF-kappaB-responsive genes MCP-1 and IkappaB-alpha) was reduced rather than increased. These data suggest that IkappaB-alpha does not form a negative autoregulatory loop for NF-kappaB in mesangial cells and may actually reduce NF-kappaB activity. This may have relevance to therapies directed at inhibition of NF-kappaB activity in mesangial cell diseases.

Animals↗
PubMedDate not supplied

Sublytic complement injury does not activate NF-kappa B, or induce mitogenesis in rat mesangial cells.

Sublytic complement injury to glomerular mesangial cells, mediated by the terminal membrane attack complex of complement (C5b-9), is a potential initiating mechanism in IgA nephropathy. Sublytic complement injury has been reported to result in the production of a variety of pro-inflammatory molecules and growth factors, including many regulated by the transcription factor NF-kappa B. To determine the importance of complement injury in the pro-inflammatory signalling which occurs in IgA nephropathy, we investigated NF-kappa B activation following sublytic complement injury to cultured rat glomerular mesangial cells (RMCs). A sublytic dose of rabbit anti-Thy 1.1 (THY) serum and normal human serum was selected based upon flow cytometry, chromium-release assay, and induction of superoxide production. No significant C5b-9-induced NF-kappa B activation was detected by electrophoretic mobility shift assays, luciferase activity of RMCs transfected with a NF-kappa B-driven luciferase reporter construct, nor by Northern blots for the NF-kappa B-responsive mRNA species monocyte chemoattractant protein-1 or I kappa B alpha. Furthermore, measurements of (3)H incorporation following sublytic complement injury showed inhibition of mesangial cell mitogenesis in comparison to the heat-inactivated serum treatment and to THY alone. The results of this study suggest that sublytic complement injury to RMC does not directly activate NF-kappa B nor induce mesangial cell proliferation in mesangial cells. Other mechanisms such as IgA immune complex formation must be required to produce these events in IgA nephropathy.

Animals↗
PubMedDate not supplied

Circulating leptin levels and weight loss in Alzheimer's disease patients.

Weight loss is common in Alzheimer's disease (AD) and is predictive of mortality. Leptin, an adipocyte-derived peptide hormone is implicated in the regulation of satiety and energy expenditure. It acts on the hypothalamus to suppress appetite and increase energy expenditure. We undertook this study to determine if inappropriately elevated leptin levels play a role in AD-associated weight loss. Serum leptin levels of 8 patients in each of the following groups were determined: (1) AD, body mass index (BMI) >25; (2) AD, BMI <20; (3) non-Alzheimer's (vascular) dementia (VaD), BMI >25, and (4) VaD, BMI <20. Mean serum leptin levels were significantly lower in below-appropriate-weight patients (both AD and VaD) than in appropriate-weight controls. Below-appropriate-weight AD patients had a significantly lower mean serum leptin concentration than appropriate-weight VaD controls. Weight loss is a feature of AD. Inappropriately elevated leptin levels do not appear to be implicated. Indeed, we have shown that the afferent limb of the leptin feedback loop is intact in below-appropriate-weight AD patients and suggest hypothalamic dysfunction may underlie this feature.

Aged↗
PubMedDate not supplied

Effect of transforming growth factor-beta 1 on plasminogen activators and plasminogen activator inhibitor-1 in renal glomerular cells.

Recent evidence suggests that the balance between serine proteases and their inhibitors is central to the maintenance of the glomerular extracellular matrix. We have characterised the urokinase type and the tissue type plasminogen activators (PA) and their inhibitor, PAI-1, secreted from glomerular epithelial and mesangial cells as well as their co-cultures and have investigated the effect of transforming growth factor-beta 1 (TGF-beta 1) on the production of such species. Similar data were derived from whole glomeruli suspensions. TGF-beta 1 increased PAI-1 production significantly in epithelial and mesangial cells as well as in whole glomeruli, while PA production was decreased; platelet-derived growth factor had no effect. These effects are consistent with a possible decrease in matrix proteolysis, suggesting a mechanism by which TGF-beta 1 may enhance mesangial matrix accumulation, a characteristic of many forms of glomerular disease.

Epithelial Cells↗
PubMedDate not supplied

Heparin-binding epidermal growth factor-like growth factor, an immediate-early gene for mesangial cells, is up-regulated in the Thy-1.1 model.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is one of five well-described growth factors which bind to and activate the EGF receptor. Since cultured mesangial cells synthesize HB-EGF and this cytokine is a potent mitogen for smooth muscle cells (SMC), a cell type similar to mesangial cells, we attempted to determine (1) whether HB-EGF mRNA is present in the proliferative phase of experimental mesangial proliferative glomerulonephritis, and (2) some of the factors which regulate its synthesis by mesangial cells. In this study we demonstrate that cultured rat mesangial cells (RMC) express HB-EGF mRNA and that transcript levels are markedly increased by serum with maximal induction occurring within 2 h. Stimulation with individual cytokines (EGF, TGF-alpha, PDGF, TGF-beta and TNF-alpha), by contrast, had only a minor effect. The increase in HB-EGF mRNA levels following addition of serum was rapid, transient and independent of protein synthesis, features characteristic of immediate-early genes. In normal rat kidneys, there was no detectable glomerular expression of HB-EGF mRNA as determined by in situ hybridization, although occasional tubular cross sections were positive. Within 30 min after induction of the Thy-1.1 model, however, cells within the glomerulus and an increased number of tubules were positive. The number of positive glomerular and tubular cells increased progressively at days 1 and 4 post-induction, but declined by day 9 and had returned to background at day 15. Within the glomerulus, HB-EGF was expressed by cells of Bowman's capsule and cells within the glomerular tuft. Using (a) combined in situ hybridization and immunohistochemical staining of the same section and (b) staining of sequential sections by immunohistochemistry or in situ hybridization, it was found that intrinsic glomerular cells which did not stain with the macrophage marker ED-1 expressed HB-EGF mRNA. Although some were probably glomerular epithelial cells because of their peripheral location, it was uncertain whether mesangial cells were also positive. Future studies will be directed towards firmer identification of the glomerular cells expressing HB-EGF mRNA and to define the functional role of HB-EGF in the Thy-1.1 model.

Animals↗
PubMedDate not supplied

Endoglin, a transforming growth factor-beta-binding protein, is upregulated in chronic progressive renal disease.

Endoglin is a non-signalling receptor for TGF-beta. In view of the importance of transforming growth factor-beta (TGF-beta) in the pathogenesis of renal disease, we have determined the distribution of TGF-beta in human glomerulonephritis. Endoglin was present within the glomerular mesangium and interstitium in normal kidneys. In diseased biopsies, there was a weak but significant correlation between staining for endoglin in the interstitium and the extent of chronic histological damage (r = 0.3343, p = 0.003). This was supported by division of biopsies into those showing mild damage and those with moderate to severe damage, where the latter group had significantly increased interstitial staining for endoglin (p = 0.0035). However, there was no correlation between mesangial staining for endoglin and specific types of glomerular pathology, such as IgA nephropathy, suggesting that the interstitial expression of endoglin is associated with increased renal damage independent of the specific type of glomerular lesion which initiates the process. There was also a positive correlation between mesangial cell staining for endoglin and interstitial endoglin expression (r = 0.3104, p = 0.003), although the former was not independently associated with chronic histological damage. These data suggest that the response of interstitial fibroblasts and mesangial cells may be linked in glomerulonephritis. Both could contribute to renal scarring by increased binding of TGF-beta which would be independent of the type of initial glomerular damage.

Antigens, CD↗