PubMed Health⌕ Search

Biomedical subjects

M W Steffes

Publications and source records attributed to M W Steffes.

At least 163 records · Page 9Linked to original sources
PubMed1976

Studies of diabetic nephropathy in animals and man.

Animal models of diabetes mellitus allow for the manipulation of the metabolic state and the performance of experiments that may shed light on the pathogenesis of diabetic nephropathy. Rats with long-standing chemically induced diabetes develop glomerular mesangial thickening and immunoglobulin and complement deposition. These glomerular changes are reversible on the transplantation of a kidney from a diabetic rat into a normal host and on cure of the diabetic state by pancreatic islet transplantation. Conversely, diabetic renal changes develop in normal kidneys transplanted into diabetic rats (within tow to four months) and humans (within two years). These studies suggest that nephropathy results from the diabetic state. The mesangium is thickened in diabetic rats, mice, and humans. In rats, mesangial function is the processing of macromolecules localized therein is disturbed in areas of mesangial pathology. The finding that glomerulopathy is accelerated in uninephrectomized diabetic rats and is retarded in rat kidneys "protected" by narrowing of the renal artery suggests that alterations in glomerular blood flow are related to the pathogenesis of diabetic glomerular damage. Marked hyperglycemia in animals and man leads to "glycogen nephrosis," which affects the distal tubule at the level of the macula densa of the juxtaglomerular apparatus (JGA). This could lead to disturbance of JGA blood pressure regulation. Disturned mesangial function may result from failure of macula densa cells to process macromolecules that have reached that site from the mesangium.

Animals↗
PubMed1976

A simple and precise method of determining true sodium, potassium, and chloride concentrations in hyperlipemia.

Sodium, potassium, and chloride levels are artifactually depressed in hyperlipemic sera. Accurate electrolyte levels are needed for management of patients with hyperlipemia, but present methods for correcting the values (serum water and/or osmolality determinations) either are technically cumbersome or fail to provide accurate data to correct the falsely low levels. Alternatively, to determine true sodium, potassium, and chloride concentrations in hyperlipemic sera, only the required electrolyte values and the triglycerides are measured. The percentage by which the measured electrolyte levels in the hyperlipemic sample must be increased to approximate the true values is given by the following equation: per cent increase = 2.1 X triglycerides (Gm./dl.) - 0.6.

Adolescent↗
PubMed1975

Glucagon biosynthesis in human pancreatic islets: preliminary evidence for a biosynthetic intermediate.

Viable pancreatic islets were isolated from the pancreas of humans using modifications of the collagenase digestion and Ficoll gradient techniques. Gel filtration of tissue extracts following islet incubation in the presence of 3H- tryptophan indicated that radioactivity becomes incorporated into at least two islet proteins. The larger of the two (LGI) has the approximate molecular size of proinsuiln and the smaller coelutes with glucagon as determined by column standardization. Radioimmunoassay of the gel filtration eluate for glucagon revealed that both molecules have glucagon immunoreactivity. Gel filtration in the presence of 8M urea did not alter the elution pattern of the LGI molecule. Polyacrylamide gel electrophoresis was performed on these glucagon immunoreactive molecules. The 3H radioactivity and the glucagon immunoreactivity of the smaller molecule were found to co-migrate electrophoretically with crystalline porcine glucagon and monodesamidoglucagon. With electrophoresis at high pH the electrophoretic mobility of the LGI molecule proved to be lower than that of glucagon. Partial tryptic degradation of the human LGI molecule yields 3H-tryptophan labeled products having charge and immunologic characteristics indistinguishable from porcine glucagon and monodesamidoglucagon. Although further investigation is indicatend may thus serve as a precursor or an intermediate in human glucagon biosynthesis.

Antigens↗
PubMed1975

Islet transplantation in diabetic rats receiving corticosteroids.

Pancreatic tissue fragments from neonatal inbred Lewis rats were distributed throughout the peritoneal cavities of isologous diabetic recipients receiving prednisolone on a schedule similar to that used in clinical transplantation beginning 9-44 days before transplantation. Plasma glucose levels in six of seven diabetic rats receiving prednislone returned to normal levels 3 weeks after transplantation. Plasma insulin levels in the animals with successful transplants reached, at 1 week after transplantation, levels measured in normal control rats, but never attained the high insulin levels observed in the normal control animals receiving steroids. As with glucose the insulin levels remained in the normal range, and the animals steadily gained weight. During i.v. glucose tolerance tests (IVGTTs) in the rats with successful transplants at 4, 11-14, and 26-29 weeks after transplantation, the glucose levels were similar to those observed during IVGTTs in the control animals before and during corticosteroid therapy. In contrast, insulin levels during the IVGTTs were lower in the rats with successful transplants than in the control rats with or without steroids; however, insulin release during the IVGTTs was rapid in all animals, both with successful transplants and controls. These observations demonstrate that islet tissue implanted in the peritoneal cavities of diabetic rats receiving immunosuppressive chronic corticosteroid therapy can respond with a rapid and sufficient release of insulin to reverse diabetes as documented by normal glucose levels under stimulated and nonstimulated conditions.

Animals↗
PubMed1975

Studies of the rate of regression of the glomerular lesions in diabetic rats treated with pancreatic islet transplantation.

Diabetes was induced in Lewis rats with streptozotocin. Six to eight months later glomeruli showed mesangial thickening: IgG, IgM and C3 were seen in large quantities in the mesangium by immunofluorescent microscopy. Ten animals then had successful pancreatic transplantation resulting in normal glucose and insulin levels within one to three weeks. Biopsies obtained within the first two weeks following transplantation demonstrated a significant reduction in mesangial thickening and in mesangial staining for IgG, IgM and C3. Three to four weeks after transplantation C3 staining was no longer detected. A gradual reduction in mesangial IgG and IgM localization continued so that by nine weeks following islet transplantation only minimal staining for immunoglobulins was present. Although mesangial thickening was reduced, this abnormality could still be detected in most animals six to nine weeks after transplantation. Three rats showed improvement in glomerular morphology within two weeks despite persistent hyperglycemia. These rats had normal insulin levels at this time. Islet transplantation in inbred diabetic rats effectively returns glucose and insulin levels to normal and results in rapid regression of the light microscopic and immunopathologic glomerular lesions. These studies support the concept of reversible mesangial dysfunction in diabetic rats.

Animals↗
PubMed1975

Plasma insulin and glucose levels in diabetic rats prior to and following islet transplantation.

Transplantation of islets of Langerhans into the peritoneal cavity of diabetic rats returns the recipients to a normal metabolic state and provides the capability to respond to a glucose stimulation with a rapid release of insulin. Of the two groups of transplanted diabetic rats studied, each had normal nonfasting glucose levels and normal glucose profiles following intravenous glucose tolerance tests. However, one group had significantly lower insulin levels than normal controls both under nonfasting conditions and 4 minutes following glucose stimulation. The other group demonstrated insulin levels greater than those of the normal controls when drawn under nonfasting conditions and essentially identical to the levels of the normal controls following a glucose load. Each transplanted group responded similarly to normal rats with a rapid release of insulin following glucose administration.

Animals↗
PubMedDate not supplied

Structural-functional relationships in type I insulin-dependent diabetes mellitus in humans.

The major renal pathologic changes of diabetes include thickening of all renal extracellular basement membranes and mesangial matrix and, to a lesser extent, mesangial cell expansion. Two renal lesions appear critical in diabetic nephropathy. Mesangial expansion out of proportion to the size of the glomerulus is closely and inversely related to measures of peripheral capillary wall filtration surface and to clinical features of proteinuria, hypertension, and decreasing glomerular filtration rate (GFR). Arteriolar hyalinosis is related to global glomerulosclerosis, and both are correlated with the clinical features of nephropathy. These lesions are markedly advanced by the time renal dysfunction is clinically detectable. Relationships of structure and function early in the course of the diabetes have not been examined satisfactorily.

Arterioles↗