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Biomedical subjects

M Mauer

Publications and source records attributed to M Mauer.

At least 55 records · Page 3Linked to original sources
PubMed1996

Growth phenotype of cultured skin fibroblasts from IDDM patients with and without nephropathy and overactivity of the Na+/H+ antiporter.

An increased activity of the Na+/H+ antiporter in cells from patients with insulin-dependent diabetes mellitus (IDDM) has been proposed as a potential marker of nephropathy. We evaluated Na+/H+ antiporter activity and its relationship to DNA and protein synthesis in cultured skin fibroblasts from patients with IDDM classified as having either overt nephropathy or absence of nephropathy on the basis of urinary albumin excretion and kidney biopsy findings. In IDDM patients with overt nephropathy, Na+/H+ antiporter activity in serum stimulated cells was increased as compared to cells from control subjects (9.62 +/- 0.89 vs. 5.67 +/- 0.97 mmol H+/min, P < 0.005, respectively) and cells from IDDM patients without nephropathy (7.22 +/- 0.67 mmol H+/min, P < 0.025). By contrast, in cells made quiescent by serum deprivation Na+/H+ antiporter activity was lower than in serum-stimulated cells and there were no significant differences between the three groups. DNA synthesis assessed by [3H] thymidine incorporation was increased in the IDDM group with nephropathy as compared to the group without nephropathy (138 +/- 14 vs. 105 +/- 13 cpm/1000 cells, respectively, P < 0.05) and as compared to control subjects (65 +/- 11 cpm/1000 cells, P < 0.001). By contrast, protein synthesis assessed by [14C] L-leucine incorporation was not increased in fibroblasts from IDDM patients with nephropathy, suggesting that cellular hypertrophy is not a feature of their altered growth phenotype. After chronic inhibition of the Na+/H+ antiporter using EIPA (25 microM), [3H] thymidine incorporation was reduced by about 20% both in cells from IDDM patients and controls. This parameter therefore remained higher in cells from IDDM patients with nephropathy than in those from controls (81 +/- 16 vs. 40 +/- 6 cpm/1000 cells, P < 0.05), while in cells from IDDM patients without nephropathy [3H] thymidine incorporation after EIPA (56 +/- 7.0 cpm/1000 cells) was intermediate between cells from controls and IDDM patients with nephropathy. We argue that cultured skin fibroblasts from IDDM patients, with nephropathy display an abnormal growth phenotype characterized by cell hyperplasia. This growth phenotype is associated with overactivity of the Na+/H+ antiporter during serum stimulation but not when cells are made quiescent and persists after inhibition of the Na+/H+ antiporter. Our data, therefore, further shows that overactivity of the Na+/H+ antiporter is not required for the expression of the altered growth phenotype of cultured skin fibroblasts from IDDM patients with nephropathy.

Adult↗
PubMed1996

Distribution of integrin subunits in human diabetic kidneys.

Integrins are cell-surface protein receptors that participate in cell adhesion to multiple extracellular matrix ligands, and consist of alpha and beta chain heterodimers. This study examined altered integrin distribution in diabetic nephropathy by investigating 12 human diabetic kidney biopsies, which were compared with normal human kidney. Diabetic nephropathy is characterized by mesangial expansion and progressive thickening of the glomerular basement membrane. Based on morphometric studies of mesangial expansion, diabetic nephropathy was determined to be moderate or severe. Three different patterns (P) of altered intensity of integrin staining were observed. In the mesangial integrin P, the intensity of integrin subunit staining of mesangial cells (alpha 1, alpha 2, alpha 3, beta 1, alpha V, alpha V beta 5) was increased in moderate diabetic nephropathy and further increased in severe diabetic nephropathy. In the epithelial integrin P, integrin subunits localized to epithelial cells (alpha V, beta 3, alpha V beta 3, alpha V beta 5) were increased to the same extent in moderate and severe diabetic nephropathy. In the endothelial integrin P, integrin subunits localized to endothelial cells (alpha 3, alpha 5, alpha 6, beta 1) were increased in moderate diabetic nephropathy but returned to normal kidney staining intensity in severe diabetic nephropathy. From these observations, it was concluded that there is significant alteration in the expression of integrin subunits in diabetic nephropathy that is related to the severity of diabetic mesangial expansion. Additionally, the spectrum of integrin subunit alteration appears to be unique to individual glomerular cell types. Given the role of integrins in cell-surface interactions with extracellular matrix components, abnormalities in the expression of these molecules may be important in the pathogenesis of diabetic nephropathy.

Adult↗
PubMed1995

Cyclosporine associated lesions in native kidneys of diabetic pancreas transplant recipients.

Five years of normoglycemia following pancreas transplantation (PT) does not ameliorate glomerular lesions in patients with their own kidneys and with long-term insulin-dependent diabetes (IDDM) (Lancet 342:1193, 1993). All these patients received cyclosporine (CsA) as part of their immunosuppression. Here we examined the relationship of CsA dose and blood levels to the presence and severity of CsA-associated renal lesions and changes in renal function in these PT patients. Renal biopsies were taken before (0) and two and five years after PT from 13 non-uremic IDDM patients and were compared with baseline and five year biopsies from 10 IDDM controls (C). CsA dose was reduced from 10 +/- 3 mg/kg/day in the first month to 5 +/- 2 in the fifth year post-PT. Creatinine clearance (CCr) decreased by 34% at one year post-PT and was stable thereafter, and did not change in C. The decline in CCr from 0 to one year was related to CsA blood levels and dose (P < 0.005) at one year. Cortical interstitial volume fraction [Vv(Int/Cortex)], the index of tubular atrophy, and % sclerotic glomeruli increased significantly from 0 to five years post-PT (P < 0.005, 0.01 and 0.001, respectively), but did not change in C. There was no significant change from 0 to two years post-PT in these lesions, while there was a clear progression from two to five years. Mean CsA dose and blood levels in the first year post-PT correlated with the increase (delta) in Vv(Int/Cortex) at five years (P < 0.05 for both).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Sequential renal biopsies in insulin-dependent diabetic patients: structural factors associated with clinical progression.

Quantitative structural studies in native kidneys of IDDM patients have almost all been cross sectional, and little is known regarding the dynamics of progression of structural lesions in relation to clinical progression. It has been suggested that interstitial may be more important than glomerular changes in determining functional outcome. This study evaluated renal structure in sequential biopsies from IDDM patients with established renal lesions to determine whether glomerular, arteriolar and interstitial changes progress together and in concordance with measures of renal function. Eleven long-term IDDM patients [age 29 +/- 10 years, duration 17 +/- 7 years (mean +/- SD)] had renal function studies and kidney biopsies performed at two occasions 5.6 +/- 1.6 years apart. HbA1 as well as creatinine clearance (CCr) did not change over this time; albumin excretion rate (AER) increased from 12 (6 to 280) to 19 (5 to 2462) [median (range)] mg/24 hr (P < 0.03). AER increased in the three patients with abnormal albuminuria at first observation, and two normoalbuminuric patients became microalbuminuric. Blood pressure (BP) did not change; however, the number of patients on antihypertensive therapy increased from 1 to 5. All structural parameters were abnormal at first evaluation. Mesangial fractional volume [Vv(mes/glom)] and mean glomerular volume increased and the surface density of the peripheral glomerular basement membrane (GBM) decreased, while GBM width did not change over the five years of the study. Also, arteriolar hyalinosis lesions progressed, while the fractional volume of cortical interstitium [Vv(interstitium/cortex)] and the percent of globally sclerosed glomeruli did not change. The only structural change that correlated with the increasing AER was the change in Vv(mes/glom). Changes in structural parameters, AER or CCr did not significantly correlate with baseline BP or change in BP over the five years. Although based on a small number of patients, this study suggests that at the stage of disease where renal lesions are established and where some IDDM patients are in transition to microalbuminuria or early clinical nephropathy, continuing mesangial expansion is the central variable. Interstitial changes were not occurring over this time. Progressive interstitial expansion at the later stages of diabetic nephropathy may thus be consequent to advanced diabetic glomerular injury.

Adult↗
PubMed1994

Glomerular structure in nonproteinuric IDDM patients with various levels of albuminuria.

Although microalbuminuria is known to foretell the later development of overt proteinuria in patients with insulin-dependent diabetes mellitus (IDDM), different investigators have reported different levels of albuminuria as being predictive. However, whether different levels of albuminuria reflect differences in glomerular structure is not well known. In this study, we divided a cohort of 66 nonproteinuric long-standing (duration 20 +/- 7 years) IDDM patients, who had both renal functional and structural studies performed, into four groups according to their urinary albumin excretion rate (AER). The several different levels of microalbuminuria previously reported to be predictive served to demarcate these groups: group I, AER < or = 22 mg/24 h (upper limit for normal in our laboratory) (33 patients); group II, AER 23-45 mg/24 h (11 patients); group III, AER 46-100 mg/24 h (13 patients); and group IV, AER 101-220 mg/24 h (9 patients). Creatinine clearance was similar in groups I, II, and III but was lower in group IV. Systemic hypertension was present in five patients in group I, one in group II, seven in group III, and five in group IV. Mean values for glomerular basement membrane (GBM) width and volume fraction of the mesangium [Vv(mes/glom)] were greater in all groups than in a group of 52 age-matched normal kidney donors (P < 0.0001). Also, filtration surface density [Sv(PGBM)], inversely related to Vv(mes/glom) (r = 0.61, P < 0.0001), was reduced in all diabetic groups compared with the normal group (P < 0.0001). Structural measures were identical in group I and II.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Pediatric renal transplants--results with sequential immunosuppression.

Cyclosporine has improved the results of renal transplantation. In 1984, we began using it as part of a sequential immunosuppression protocol (MALG, AZA, P, and delayed administration of CsA) in our pediatric renal transplant recipients. We studied the outcome of the 131 pediatric renal transplants (less than or equal to 18 years of age at transplant) performed at our institution between June 1984 and March 1991. We compared these results with the 144 similar transplants performed since January 1980 that did not involve CsA immunosuppression. In the sequential immunosuppression group, there were 97 primary (74%) (26 [27%] cadaver, 71 [73%] living donor [LD]) and 34 (26%) retransplant (23 [68%] CAD, 11 [32%]) recipients. Age at transplant (mean +/- SD) was 7.4 +/- 5.5. Overall, 1-year actuarial graft survival was 93%; 1-year patient survival was 100%. The mean number of hospital readmissions was 3.0 +/- 3.5; 26 (20%) were readmission-free. The mean number of rejection episodes was .87 +/- 1.3 per patient; 73 (56%) were rejection-free. Importantly, LD (vs. CAD) recipients had fewer rejection episodes (P = 0.06). In the first post-transplant year, the serum creatinine level was significantly lower in primary (vs. retransplant) recipients and in LD (vs. CAD) recipients (P less than 0.05). In the 144 patients not receiving CsA, there were 129 (90%) primary (27 CAD, 102 LD) and 15 (10%) retransplant (7 CAD, 8 LD) recipients. Age at transplant was 6.9 +/- 5.3 years. The 1-year actuarial graft survival rate was 82%; the 1-year patient survival rate was 94%. The mean number of hospital readmissions was 3.3 +/- 2.3; 5 (8%) were readmission-free. The mean number of rejection episodes was 1.2 +/- 1.5; 27 (45%) were rejection-free. There was no difference in the serum creatinine level based on donor source or transplant number. Sequential immunosuppression has significantly improved patient (P = 0.003) and graft survival (P = 0.004) rates. Comparing sequential vs. non-CsA immunosuppression, there was no difference in the number of readmissions (P = 0.47), number of rejection episodes (P = 0.17), or serum creatinine level. The number of rejection-free patients was significantly lower in LD (vs. CAD) recipients (P less than 0.05). There was no evidence of progressive deterioration in renal function in the sequential (vs. non-CsA) recipients.

Adolescent↗
PubMed1992

Renal transplantation in the first year of life: the treatment of choice for infants with end-stage renal disease.

The treatment of choice for end-stage renal failure within the first year of life is controversial. Between September 1970 and February 1991, we performed 28 kidney transplants (27 primary, 1 retransplant, 23 living donor, 5 cadaver) in infants less than 1 yr of age (mean, 7 +/- 2 months; range, 6 wk to 12 months). The 1-yr patient survival rate for living donor recipients was 100% versus 20% for cadaver recipients (P = 0.0001). The 1-yr graft survival rate for living donor recipients was 96% versus 20% for cadaver recipients (P = 0.001). The 1-yr patient survival rate for cyclosporin A (CSA) recipients (N = 12) was 100% versus 75% for non-CSA recipients (P = 0.03). The 1-yr graft survival rate for CSA recipients was 92% versus 75% for non-CSA recipients (P = 0.08). There was no difference in the number of rejection episodes or serum creatinine levels in CSA versus non-CSA recipients. Compared with pretransplant values, the mean posttransplant standard deviation scores (SDS) for height (N = 18), weight (N = 22), and head circumference (N = 8) improved: height SDS from -1.9 to -1.5 (not significant); weight SDS from -2.5 to 0.6 (P less than 0.0005); head circumference SDS from -2.0 to -0.7 (P = 0.01). Because no other renal replacement therapy can match these results, we conclude that renal transplantation is the treatment of choice for infants with end-stage renal failure.

Evaluation Studies as Topic↗
PubMed1985

Skeletal muscle basement membrane in maturity-onset diabetes in the young.

We have studied skeletal muscle capillary basement membrane width (CBMW) and intensity of skeletal muscle extracellular basement membrane staining for albumin and IgG in eight families with maturity-onset diabetes in the young (MODY). Ninety-two MODY patients were identified. Sixty-three of these patients, 33 relatives with nondiagnostic oral glucose tolerance studies, and 61 normoglycemic relatives were studied for glucose and insulin. Twenty-six of these MODY patients, 20 normoglycemic relatives, and 16 unrelated normal controls had skeletal muscle capillary morphologic studies. The muscle capillary basement membrane was significantly increased in MODY patients younger than 40 yr when compared with unrelated normal subjects and relatives of the same age (P less than 0.001). However, in these families, the CBMW of MODY patients showed no significant thickening with age (slope = 0.45, P less than 0.14), as expected and seen in the normal subjects and in the normoglycemic relatives of the patients (slope = 1.21, P less than 0.001). The slope derived from the linear regression of age and CBMW in MODY patients (0.45 +/- 0.29) was significantly less (P less than 0.05) than that of the nondiabetic subjects (1.21 +/- 0.19). The mean intensity of skeletal muscle extracellular basement membrane staining for albumin was higher in MODY patients (1.1 +/- 0.15) than in unrelated normal subjects (0.7 +/- 0.1, P less than 0.025) and normal MODY family members (0.6 +/- 0.08, P less than 0.01). The unexpected absence of basement membrane thickening with age in the MODY patients may explain the paucity of vascular complications that have been reported by some.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

The value of needle renal allograft biopsy. I. A retrospective study of biopsies performed during putative rejection episodes.

Following renal transplantation, immunosuppression is usually increased to treat presumed rejection episodes. However, a) many conditions mimic rejection in the post-transplant period, and b) many rejection episodes are irreversible. As increased immunosuppressive therapy is associated with an increased risk of infection, it would be ideal to limit antirejection therapy to only the rejection episodes that are reversible. The role of percutaneous allograft biopsy was studied as an aid to decide which patients to treat for rejection, to limit unnecessary immunosuppression and to predict allograft survival. One hundred thirty-five patients with suspected rejection underwent 206 allograft biopsies without complication. Two hundred four biopsies were available for study. Biopsies were coded on a 1-4 scale (minimal, mild, moderate, severe) for acute and chronic tubulointerstitial infiltrate and vascular rejection, as well as no rejection (e.g., recurrence of original disease). Treatment decisions were made on the basis of the biopsy combined with clinical data. All patients have been followed two years and outcome correlated with biopsy findings (death, nephrectomy, and return to dialysis defined as kidney loss). The results were the following: 1) biopsies represented changes within the kidney. Of 16 kidneys removed within one month of biopsy, no nephrectomy specimen showed less rejection than that seen on biopsy. 2) Eighty-one biopsies (39.7%) led to tapering or not increasing immunosuppression (either no rejection, minimal rejection, or irreversible changes). 3) Kidneys having either severe acute or chronic vascular rejection (less than 30% function at three months) had significantly (p less than 0.05) decreased survival three to 24 months postbiopsy than those with minimal or mild vascular rejection or tubulointerstitial infiltrate (83% function at three months). 4) Kidneys with moderate chronic vascular rejection and those with severe acute tubulointerstitial infiltrate had significantly (p less than 0.05) decreased survival at six to 24 months. 5) Kidneys with moderate chronic vascular rejection (MCV) without an acute infiltrate (ATI) had significantly better survival than those having both MCV and ATI. 6) Similarly, kidneys having severe ATI alone had better survival than those with ATI plus vascular rejection. It was concluded that a) percutaneous allograft biopsy can be done without graft loss or infection; b) biopsy represents changes throughout the kidney; c) biopsy aids in deciding when to treat for rejection and in deciding when to withhold increased immunosuppression, and d) allograft biopsy predicts the outcome of treatment of a rejection episode.

Biopsy, Needle↗
PubMed1976

B cell ontogeny in rabbits. Immunofluoresecent localization of B cells in fetal and neonatal rabbits.

The mammalian equivalent of the Bursa of Fabricius, the organ responsible for B cell maturation in avian species, has not been identified despite anatomic and ablative studies which suggest that the gut-associated lymphoid tissues (GALT) subserve this function. By analogy to the Bursa, the mammalian organ directing B cell ontogeny should be the site where IgM-bearing cells (B cells) are first identifiable. In this study, fluorescein-tagged heavy chain specific antirabbit IgM is used to localize initial sites of B cell appearance in rabbit fetal and neonatal lymphoid tissues. IgM-bearing cells are found 2 days before birth in the thymus and 1 day before birth in GALT. Immunoglobulin-bearing cells in spleen, lymph node, and bone marrow are undetectable until after birth. B cells bearing the IgM marked precede the appearance of IgG-bearing cells by 1 to 4 days in all instances. Intraperitoneal implantation of Millipore chambers containing immature fetal thymic tissue into neonatal hosts reveals that in situ development of IgM cells takes place independent of host cell traffic. The results suggest that B cell ontogeny in mammals is more complex than in avian species and demonstrates probable involvement of the thymus in the maturational process.

Animals↗
PubMed1975

Deafness and renal failure due to potassium bromate poisoning.

Several substances are known to have a profound effect on both the kidney and the inner ear. The aminoglycoside antibiotics are toxic to both of these organs. Ethacrinic acid and furosemide affect transport mechanisms in the loop of Henle as well as the inner ear. In addition, studies have suggested antigenic similarities between the stria vascularis of the cochlea and the renal tubules. This report of potassium bromate poisoning and its resultant deafness and renal failure further emphasizes the curious relationship between these two organ systems.

Acute Kidney Injury↗