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Biomedical subjects

R J Glassock

Publications and source records attributed to R J Glassock.

At least 19 recordsLinked to original sources
PubMed1992

Early increased renal procollagen alpha 1(IV) mRNA levels in streptozotocin induced diabetes.

Changes in renal procollagen mRNA levels were measured shortly after the induction of streptozotocin induced diabetes in the rat. "Medullary" procollagen alpha 1(IV) levels seven days after diabetes induction was significantly higher in untreated diabetic rats (DM, N = 12; 244 +/- 57% of the mean control value), than in diabetic rats receiving small doses of insulin insufficient to achieve euglycemia (NPH, N = 10; 87 +/- 12%) and in diluent injected nondiabetic control rats (C, N = 15; 100 +/- 12%; P less than 0.01, DM vs. C and DM vs. NPH). "Medullary" procollagen alpha 1(I) mRNA levels were numerically increased in DM to a lesser degree (141 +/- 5%, ANOVA not significant) compared to C (100 +/- 13%), and this small increment was further normalized by insulin treatment (NPH, 120 +/- 11%). A trend for increased beta-actin mRNA levels in DM did not reach significance (P greater than 0.05). Increases in "medullary" procollagen mRNA levels did not correlate with kidney weight, glomerular tuft volume, creatinine clearance, food intake, or body weight gain, and occurred when renal morphology was normal by light microscopy. Statistically significant but weak correlations were noted between the serum glucose levels and "medullary" procollagen alpha 1(IV) mRNA levels (r = 0.43, P less than 0.05). In addition, weak correlations were noted between glycosuria and "medullary" procollagen alpha 1(I) levels (r = 0.38, P less than 0.05). In situ hybridization studies localized the increased procollagen alpha 1(IV) mRNA levels predominantly in the DM group primarily in the deep cortex and medullary outer stripe of proximal tubules. Glomerular procollagen alpha 1(IV), alpha 1(I), alpha 1(III) and beta-actin mRNA levels were not increased in untreated diabetic rats 7 or 28 days after diabetes induction. Thus, tubular procollagen alpha 1(IV) mRNA levels increased prior to any measurable change in glomerular levels and were ameliorated by insulin administration.

Animals↗
PubMed1992

Secondary membranous glomerulonephritis.

Membranous glomerulonephritis of defined aetiology (secondary MG) is a common finding, particularly in children and older adults. Secondary MG can be readily detected by a combination of clinical, serological and morphological analysis in a majority of instances. Recognition of secondary MG has significant prognostic and therapeutic implications.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1992

Treatment of immunologically mediated glomerular disease.

Many immunologically mediated glomerular diseases can be successfully treated, but clinicians should be wary of unproven claims of efficacy, be cognizant of long-term deleterious effects of treatment, and should select patients with a careful eye on the natural history of the untreated disorder. It is hoped that as we gain a better understanding of the etiology and pathogenesis of the specific entities that a more rational form of therapy will emerge. The powerful tools of molecular biology and our better understanding of the inflammatory and scarring processes may provide new, highly effective and safe approaches to treatment. Like their predecessors, these approaches, however, will require very careful evaluation in human subjects by prospective controlled clinical trials. Even if we cannot favorably influence the immunological processes responsible for glomerular disease, attention to non-immunologic factors responsible for progression of disease, such as hypertension, may substantially slow the rate of progression of disease even in those patients whose fundamental disease process cannot be arrested or cured.

Glomerulonephritis↗
PubMed1992

Laminin B1 is preferentially expressed in the cortex of rat kidney and is not affected by cyclosporine administration.

Cyclosporine has proven beneficial as an immunosuppressive agent for organ rejection in kidney transplants as well as in heart and liver transplants. Cyclosporine administration, however, is associated with certain adverse effects, one of the most important being chronic nephrotoxicity characterized by focal cortical scarring. Recent experimental data show involvement of type I and possibly type IV collagens in this process. Because laminin represents another potential extracellular matrix target, we examined the effects of cyclosporine administration in rats on the expression of laminin at the messenger ribonucleic acid (mRNA) and protein levels. In untreated normal rats, laminin B1 mRNA is preferentially expressed in the renal cortices, as demonstrated by northern blots. Daily administration of cyclosporine leads to focal cortical interstitial fibrosis and tubular atrophy by 4 weeks with, as shown previously, elevated procollagen alpha-1 (type I) mRNA levels at 1 and 4 weeks. In contrast, the amounts of message for laminin B1 remain identical after 1 week and 4 weeks of cyclosporine administration, despite the development of fibrosis at 4 weeks. Similar results were obtained with antilaminin antibody. We conclude that laminin is abundant in renal cortical tissues as compared with its medullary contents and is not altered in the process of renal cortical fibrosis induced by cyclosporine.

Animals↗
PubMed1991

Dimethyl sulfoxide enhances hexose monophosphate shunt activity in cultured glomerular mesangial cells, leukocytes and erythrocytes.

The effect of dimethyl sulfoxide (DMSO) on the rate of glucose oxidation by cultured rat glomerular mesangial cells, human erythrocytes and peritoneal exudate cells was studied. Mesangial cells, erythrocytes and peritoneal exudate cells incubated with DMSO showed enhancement of 14CO2 production from D-[1-14C] glucose but not from D-[6-14C] glucose. The concentration of DMSO required to stimulate respiratory burst activity was lowest for erythrocytes and highest for peritoneal exudate cells. Studies utilizing tritiated deoxyglucose revealed that the increased glucose oxidation associated with DMSO exposure was not due to increased transmembrane glucose movement at low concentrations of DMSO, and only partially responsible at high concentrations of DMSO. This study documents the ability of DMSO to specifically enhance the activity of the hexose monophosphate shunt pathway in all cells studied. The precise mechanism whereby DMSO stimulates shunt activity remains unknown.

Animals↗
PubMed1991

The therapy of idiopathic membranous glomerulonephritis.

This analysis of IMG has focused on the long-term natural history and current approaches to therapy of this disorder. It seems clear that IMG is intrinsically a relatively benign disease, particularly in certain populations. Risk factors for an unfavorable course can often be identified at the discovery of disease. For example older age at onset, male sex, very heavy proteinuria (greater than 10 g/d), sustained hypertension, impaired renal function, and significant chronic tubulointerstitial lesions in the initial renal biopsy all portend an unfavorable outcome. Contrariwise, patients lacking these prognostic features usually do quite well with a high likelihood of spontaneous complete or partial remissions and stable renal function. Once a complete remission has occurred, whether spontaneous or therapy induced, the long-term evolution of the disorder is quite favorable. Some patients may present with what appears to be "idiopathic" MGN, only to later demonstrate underlying disease, such as neoplasia, chronic viral infection, or systemic lupus erythematosus. Glucocorticoids alone, particularly when administered orally, do not seem to have significant beneficial effects over the long term; however, high-dose intravenous methylprednisolone may at times reverse declining renal function in patients with severe nephrotic syndrome. A small subset of patients may display a remitting and relapsing course following treatment with oral glucocorticoids, resembling to some extent patients with minimal change disease. Combination of alkylating agents, either cyclophosphamide or chlorambucil with glucocorticoids is very likely beneficial for the group of patients having an intrinsically unfavorable prognosis or for patients who demonstrate progressive renal insufficiency. At the present time it is not known whether regimens that involve long-term therapy with oral cyclophosphamide combined with glucocorticoids are superior to, equivalent to, or inferior to regimens that involve the cyclical use of intravenous methyl-prednisolone oral prednisone, and oral chlorambucil. Very long-term use of cyclophosphamide, in excess of 12 months, is probably associated with unacceptable long-term risks, particularly the emergence of neoplasia. Long-term follow-up, more than 10 years, will be required to establish the magnitude of the oncogenic potential of existing shorter term regimens of cyclophosphamide-glucocorticoid combinations and for cyclical regimens using chlorambucil. Further data is required to establish the role of cyclosporine, nonsteroidal antiinflammatory agents and intravenous immunoglobulins in the treatment of patients with IMG. ACE inhibitors, sometimes combined with nonsteroidal antiinflammatory agents, may have some usefulness in patients with heavy proteinuria and declining but not advanced renal failure.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkylating Agents↗
PubMed1990

Human immunodeficiency virus (HIV) infection and the kidney.

Since the first report on the acquired immunodeficiency syndrome (AIDS) in 1981, organ involvement of AIDS has increased. We discuss the effect of human immunodeficiency virus (HIV) infection, the causative agent of AIDS, on the field of nephrology. Hyponatremia, the commonest fluid and electrolyte abnormality, is caused by various pathophysiologic mechanisms, including adrenal insufficiency. The renal parenchymal complications are diverse, but a new entity, HIV-associated nephropathy, is becoming recognized because of its characteristic clinical and pathologic features, including the fact that it causes irreversible renal failure. HIV infection in patients with end-stage renal failure, both before and after initiation of maintenance dialysis, is a significant problem. The present methods of preventing spread of virus in dialysis units seem successful. Few patients who are infected with HIV or who have AIDS have had renal transplantation, although unsuspected viral infection of cadaveric organs remains a concern.

AIDS Serodiagnosis↗
PubMed1990

Focus on proteinuria.

The treatment of glomerular proteinuria may be directed at: (1) control of basic disease processes; (2) interference with mediator systems; (3) modulation of the physiological determinants of glomerular permselectivity. Glucocorticoids and immunosuppressant agents largely exert their putative beneficial effects through actions on basic processes. Agents which affect mediator systems show great promise but the multiplicity of mediators may frustrate therapeutic efforts. Altering the physiologic determinants of proteinuria, as with diet, angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory agents may be quite useful. The antiproteinuric effects of these maneuvers may not only reduce the impact of proteinuria per se but also retard the rate of progression of renal failure which so frequently accompanies many of the states of abnormal glomerular proteinuria.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Sex vulnerability in the subtotal nephrectomy model of glomerulosclerosis in the rat.

Unilateral nephrectomy and contralateral ligation of two thirds of the renal arterial circulation were performed on male (N x M, n = 6) and female (N x F, n = 7) Sprague-Dawley rats. Sham nephrectomies were performed in 16 male and female control rats (SN x M, n = 8; SN x F, n = 8). Creatinine clearance corrected for body weight and systolic arterial blood pressure were equal in both nephrectomized groups after 1, 3, and 5 weeks. The appearance of proteinuria was delayed in N x F and was still significantly less than N x M after 5 weeks (79 +/- 22 vs 30 +/- 12 mg per 24 hours, p less than 0.05). Glomerular visceral epithelial cell protein reabsorption droplets and vacuolization were equal in N x M and N x F. N x F exhibited one fifteenth of the glomerulosclerosis seen in N x M (p less than 0.01). In addition, there was one fourth of the mesangial expansion, but this trend did not reach statistical significance (p greater than 0.05). Mean glomerular volume was similar in male and female sham-operated (p greater than 0.05) and nephrectomized rats (p greater than 0.05), and nephrectomy resulted in hypertrophy in both groups (p less than 0.01). Glomerular procollagen alpha 1(IV) mRNA levels were higher in N x M than in all other groups (p less than 0.05) and correlated with mesangial expansion and glomerular sclerosis (p less than 0.01) but not with systemic hypertension, proteinuria, or epithelial cell changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗