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Biomedical subjects

M W Steffes

Publications and source records attributed to M W Steffes.

At least 91 records · Page 5Linked to original sources
PubMed1985

Studies of kidney and muscle biopsy specimens from identical twins discordant for type I diabetes mellitus.

To distinguish metabolic from genetic factors in the development of microangiopathy in diabetes, we evaluated biopsy specimens of kidney and quadriceps muscle from seven pairs of identical twins who were discordant for Type I (insulin-dependent) diabetes mellitus. Two of the diabetic patients had clinical diabetic nephropathy, including hypertension, marked albuminuria, and a substantially reduced creatinine clearance; the other five had normal renal function and only minor clinical indications of complications. All the twins of the diabetic patients had normal glomerular basement membrane widths and normal fractional volumes of the glomerular mesangium. Values for glomerular basement membrane width, tubular basement membrane width, and mesangial volume in each diabetic twin exceeded the values in the respective sibling (P less than or equal to 0.0035), even if the value in the diabetic twin lay within established normal ranges. Values for muscle capillary basement membrane width in the diabetic twins did not differ from those in their siblings (P = 0.5). Our observations suggest that the metabolic abnormalities of diabetes are necessary, if not sufficient, for the development of glomerular abnormalities. We also conclude that in diabetic patients, alterations in muscle capillary basement membrane width do not necessarily accompany pathologic lesions in the kidney.

Adult↗
PubMed1985

Relationship of renal size to nephropathy in type 1 (insulin-dependent) diabetes.

Thirty-five patients with Type 1 (insulin-dependent) diabetes mellitus and 90 normal subjects had renal size (renal area index) determined by X-ray and also had examination of renal biopsies by light and electron microscopy. Renal area index of 206 +/- 32 cm2/1.73 m2 (mean +/- SD) in the Type 1 diabetic patients exceeded that in the normal subjects (180 +/- 25 cm2/1.73 m2, p less than 0.001). In the diabetic patients, the renal area index correlated with creatinine clearance (r = +0.43, p less than 0.05), but did not correlate with urinary albumin excretion, or the electron microscopic measurements of percentage total mesangium and glomerular basement membrane width. In diabetic patients with clinical nephropathy or severe glomerulopathy on biopsy, the kidneys may remain large. Thus, renal size does not indicate the severity of diabetic renal lesions on biopsy.

Adolescent↗
PubMed1985

Effects of mesangial localization of polyvinyl alcohols on glomerular basement membrane thickness.

We studied the effects of mesangial localization of polyvinyl alcohols (PVA) on glomerular basement membrane (GBM) thickness in inbred Lewis rats. To avoid possible influences of PVA redistribution after localization in liver, lung, and other organs, the kidneys of rats given PVA were transplanted into uninephrectomized normal rats. Normal kidneys transplanted into normal rats served as a control. GBM thickness at the time of transplantation was the same in PVA kidneys as in normal kidneys. However, by 18 weeks post-transplant GBM thickness was greater in PVA kidneys, and this increase was sustained at 30 weeks. Within the glomeruli of PVA kidneys, lobules with marked mesangial PVA accumulation had more marked GBM thickening than lobules with little or no PVA accumulation. It is concluded that changes within the mesangium can influence GBM thickness. Whether this represents a direct effect of mesangial architectural distortion, a consequence of local phlogistic activities such as the influx of macrophages into the mesangium of glomeruli with PVA localization, or the result of intraglomerular hemodynamic perturbations is unclear.

Animals↗
PubMed1985

Use of the dexamethasone-adrenocorticotropin test to assess the requirement for continued glucocorticoid replacement therapy after pituitary surgery.

We assessed the need for continued glucocorticoid replacement therapy in postsurgical pituitary tumor patients using a dexamethasone-ACTH test. The patients received 1 mg dexamethasone, orally, at 2300 h and 250 micrograms synthetic ACTH (Cosyntropin), iv, at 0800 h the next morning. The mean +/- SD integrated cortisol response for a 2-h period of the 31 pituitary tumor patients [1264 +/- 924 micrograms X min/dl (34.87 +/- 25.49 mumol X min/liter)] was significantly less (P less than 0.005) than that of 25 normal subjects [3331 +/- 544 micrograms X min/dl (91.90 +/- 17.04 mumol X min/liter)]. Replacement glucocorticoids were abruptly discontinued in 11 patients with responses above 1450 micrograms X min/dl (40.01 mumol X min/liter). No clinical or laboratory evidence of adrenal insufficiency occurred as long as 15 months after discontinuation. Metyrapone tests, however, in the 11 glucocorticoid-withdrawn patients revealed a reduced mean +/- SD serum 11-deoxycortisol level compared with that of 10 normal subjects [8.9 +/- 4.7 vs. 15.6 +/- 5.0 micrograms/dl (0.26 +/- 0.13 vs. 0.45 +/- 0.16 mumol/liter); P less than 0.005]. Our results indicate that the dexamethasone-ACTH test is useful in identifying patients in whom replacement glucocorticoid therapy can be safely withdrawn under nonstressed conditions. The test can be simplified to one plasma cortisol level determined 30 min after ACTH administration.

Adrenocorticotropic Hormone↗
PubMed1984

Rejection of established mouse pancreatic islet allografts by active immunization requires class I (H-2 K, D) antigen disparities.

In certain donor-recipient mouse strain combinations with class I (H-2 K, D, and K + D) or with classes I and II (H-2 D + I) disparities the incidence of islet allograft rejection is low. Furthermore pancreatic islet allografts transplanted between strains with class II (H-2 Ia) differences alone are rarely acutely rejected. In this experiment the ability of donor strain or third-party allogeneic splenocytes (active immunization) to induce rejection of established (greater than 100 days) islet allografts when the donor and recipient differed only for class I or class II antigens was tested. Class I disparate islet allografts are rejected if challenged with donor or third-party allogeneic splenocytes. The frequency of rejection is similar (80-89%) if the third-party splenocytes share the class I allele with the islet donor strain. In contrast, class II disparate islet allografts are not rejected after challenge with donor splenocytes or third-party splenocytes even when the third-party strain shares the class II disparity with the islet donor strain as well as class I antigens common to the donor and recipient. Furthermore, rejection of class II disparate islets did not occur following passive transfer of recipient strain splenocytes sensitized in vitro to donor strain lymphocytes. These results show that rejection of established islet allografts can only be induced if (1) the islet graft expresses H-2 K or H-2 D gene products that are different than the recipient strain, i.e., only class I antigens can serve as targets; and (2) challenging splenocytes also have class I disparities with the recipient.

Animals↗
PubMed1984

Structural-functional relationships in diabetic nephropathy.

Renal biopsies in 45 patients with insulin-dependent diabetes mellitus (IDDM) were examined by semiquantitative light microscopy and quantitative electron microscopic stereologic morphometry. In these 14 males and 31 females, aged 13-52 yr, who had had IDDM for 2.5-29 yr there was no strong relationship between either glomerular basement membrane (GBM) thickness or mesangial expansion and duration of IDDM. There was only a weak relationship between the thickness of the GBM and expansion of the mesangium. Thus, GBM thickening and mesangial expansion in IDDM occur at rates that often differ from one another and that vary greatly among patients. The clinical manifestations of diabetic nephropathy, albuminuria, hypertension, and decreased glomerular filtration rate related poorly or not at all to GBM thickening. In contrast, all light and electron microscopic measures of mesangial expansion were strongly related to the clinical manifestations of diabetic nephropathy, although in the absence of these clinical findings, it was not possible to predict the severity of any of the diabetic glomerular lesions. Mesangial expansion had strong inverse correlations with capillary filtering surface area density. It is hypothesized that mesangial expansion could lead to glomerular functional deterioration in IDDM by restricting the glomerular capillary vasculature and its filtering surface. However, capillary closure, glomerular sclerosis, and interstitial fibrosis could also contribute to the clinical manifestations of this disorder.

Adolescent↗
PubMed1984

Concanavalin A and alloxan interactions on glucose-induced insulin secretion and biosynthesis from islets of Langerhans.

The pretreatment of isolated islets of Langerhans with concanavalin A (Con A) completely blocks alloxan from suppressing the insulin release response to glucose. The lectin itself inhibits insulin secretion. This effect is dose dependent and reversible. Con A, however, has no protective action against the inhibition of glucose-induced insulin biosynthesis in islets exposed to alloxan. The protective action of Con A on alloxan toxicity is likely to be at the beta-cell surface at a membrane recognition site for glucose as a stimulus for secretion. The insulin biosynthetic effect of glucose appears to be mediated through a separate mechanism.

Alloxan↗
PubMed1984

A fundamental approach to the diagnosis of diseases of the thyroid gland.

Technologic advances have given the clinician and the laboratory a large armamentarium of tests permitting measurement of virtually every aspect of thyroid function. Ready availability at relatively low cost from clinical laboratories allowed these tests to be applied widely to patients. As this occurred, it became evident that abnormal test results were due to nonthyroidal illness in euthyroid sick patients far more often than true indicators of a thyroid disorder. Thus, despite the elegance of today's thyroid function tests, their proper use and interpretation still require careful observation of the patient's symptoms and signs and assessment of the overall clinical situation of the patient. Despite the proliferation of thyroid function tests, just three tests, free-T4 index, free-T3 index, and TSH, suffice for the evaluation of the thyroid status of all but a very few patients. In the form of an algorithm we have outlined a logical sequence for the development and interpretation of thyroid function tests that prompts the clinician to integrate the results with clinical assessment.

Humans↗
PubMed1983

H-2 antigen class: effect on mouse islet allograft rejection.

Rejection of mouse pancreatic islet allografts occurred in a high percentage of donor recipient combinations identical for H-21-region antigens and differing at H-2K and H-2K + H-2D without I-region disparities. The results suggest that disparities in major histocompatibility complex antigens of class I (H-2K and H-2D) alone are capable of eliciting islet allograft rejection, and that lack of a stimulus from class II (I-region) alloantigens does not ensure permanent islet allograft survival.

Animals↗
PubMed1983

Failure to find amyloidosis in dogs treated with long-term intravenous insulin delivered by a totally implantable pump.

We examined tissues of seven non-diabetic mongrel dogs and four diabetic beagle dogs treated with constant insulin infusion via totally implantable pumps for from 210 to 880 days. Kidney and skeletal muscle tissue from all dogs were stained with Congo Red and thioflavin-T and appropriately examined. Kidney tissues from the beagle dogs were examined by electron microscopy. No amyloid deposits were found in any of these tissues. Thus, we cannot confirm an earlier report of amyloid occurring in dogs given long-term intravenous insulin. It is concluded that amyloidosis is not a necessary complication of long-term intravenous insulin infusion in dogs.

Amyloidosis↗
PubMed1983

Differences in susceptibility to rejection of mouse pancreatic islet allografts disparate for class I or class II major histocompatibility antigens.

Pancreatic islet B cells express class I but not class II antigens, and removal of Ia positive passenger cells from H-2 allogeneic islets by anti-Ia serum and complement leads to permanent allograft survival. A test was made of whether the same result can be achieved by genetically removing the Ia stimulus by performing mouse islet allografts in congenic donor-recipient combinations differing at the H-2 K only, D only, or K + D regions. Mice disparate for class I antigens (H-2 K, D, and K + D) alone reject islet allografts, suggesting that Ia positive passenger cells may be involved in presentation of class I disparities. Established islet allografts appear to be sensitive to rejection induced by injection of donor strain splenocytes when donor and recipient differ for class I (H-2 D alone and D + I) but not class II (H-2 I alone) antigens. These results are consistent with the hypothesis that pancreatic islet allografts do not express class II target antigens, but do express class I antigens that in long-established pancreatic islet allografts are capable of acting as targets but not in initiating an immune response.

Animals↗
PubMed1983

Glomerular manifestations of diabetes in the BB rat.

Morphologic characteristics of the renal glomeruli and tubules of BB rats with spontaneous diabetes mellitus were studied at 30 weeks' duration of diabetes. Whereas the glomerular basement membrane (GBM) was significantly thickened, no changes in the diabetic glomeruli were seen in the peripheral capillary wall area and in the fractional volumes of the mesangial cells or of the mesangial matrix. Light microscopy of the diabetic kidneys were normal, and immunofluorescent examination of diabetic glomeruli showed no increased accumulation of albumin, C3, or IgG. Diabetic rats had increased renal blood flow and glomerular filtration rates. Diabetic rats at 7, 17, and 30 weeks excreted normal amounts of urinary albumin. Thus kidneys of the BB diabetic rat differ from other experimental models of diabetes in that GBM thickening occurs in the absence of mesangial changes and of increased albuminuria. These studies suggest that the mesangium may influence glomerular permeability in diabetes, while thickening of the GBM in diabetes does not necessarily coincide with increased urinary albumin excretion. Furthermore, these results are consonant with the hypothesis that genetic factors may influence the pathological expression of diabetic nephropathy in rats.

Animals↗
PubMed1983

Lack of donor-specific tolerance in mice with established anti-Ia-treated islet allografts.

Pancreatic islet allografts pretreated in vitro with monoclonal Ia antibody and transplanted beneath the renal capsule result in normoglycemia beyond 100 days in streptozotocin-induced diabetic recipient mice that differ only at H-2 K, H-2 K + I, or H-2 K + I + D from the donors. Mice with established islet allografts are not tolerant of donor-specific skin or islet antigens, but rather reject donor skin grafts in an accelerated fashion. Established anti-Ia antibody pretreated islet allografts continue to express target antigens and remain susceptible to rejection after challenge with donor skin grafts.

Animals↗
PubMed1983

The development of lesions in the glomerular basement membrane and mesangium after transplantation of normal kidneys to diabetic patients.

Renal allograft biopsies at the time of transplantation (baseline) and 2 yr later were obtained in 6 type I diabetic and 12 nondiabetic patients and studied for glomerular basement membrane (GBM) and mesangial changes. Diabetic patients had significantly greater GBM thickness compared with nondiabetics at 2 yr (P = 0.05, rank sum test), and the increase in GBM thickness comparing baseline and 2-yr biopsies was greater in the diabetic compared with nondiabetic patients (P = 0.005, rank sum test). Similarly, diabetic patients developed significant mesangial thickening by light microscopy while no changes were observed in nondiabetic patients (P = 0.001). Electron microscopic morphometric analysis of the percentage of total mesangium was not different on comparing diabetic and nondiabetic patients at 2 yr. There was an increase in the matrix component of the mesangium in the diabetics at this time, although this did not reach statistical significance (P = 0.06). In addition, the surface density of the peripheral glomerular capillary wall, presumably reflecting mesangial expansion, was decreased in the diabetic and unchanged in the nondiabetic patients (P = 0.005). These studies document, for the first time, the development of GBM and mesangial lesions of diabetic nephropathy in normal living related donor and cadaver kidneys transplanted into diabetic patients and support the hypothesis that these lesions are secondary to the diabetic state.

Adult↗