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Biomedical subjects

T B Wiegmann

Publications and source records attributed to T B Wiegmann.

At least 19 recordsLinked to original sources
PubMed1997

Renal structural-functional relationships in early diabetes mellitus.

To define the earliest renal morphological changes in patients with type I diabetes, we studied renal function and morphometric analysis of renal biopsies in 59 patients with diabetes for 5-12 years and normal blood pressure, normal creatinine clearance (CCr), and negative dipstick urinary protein. Arteriolar hyalinization and intimal fibrous thickening were noted in 43%. Glomerular basement membrane thickness and fractional mesangial volume were increased in 51% and 56%, respectively. The pre-pubertal and post-pubertal years of diabetes were associated with similar degrees of renal structural changes, but during the pre-pubertal years normal urinary albumin excretion (UAE) was seen. Principal factor analysis of morphometric structural parameters yielded four clusters of variables: "glomerular size" correlated with patient age, CCr, and UAE; "peripheral capillary decrease" correlated with glycosylated hemoglobin, diastolic blood pressure, glomerular filtration rate, and UAE; "mesangial increase" correlated with UAE; and "interstitial scarring" correlated with diastolic blood pressure. This study provides unique documentation of renal structural abnormalities which precede clinically evident renal functional abnormalities and documents that these early structural abnormalities are present in the pre-pubertal years of diabetes as well as postpuberty, and are associated with each other in constellations that correspond to postulated mechanisms in diabetic nephropathy.

Adolescent↗
PubMed1996

Fluorescent analysis in polarized MDCK cell monolayers: intracellular pH and calcium interactions after apical and basolateral stimulation with arginine vasopressin.

Intracellular calcium ([Ca2+]i) and hydrogen ion concentrations (pHi) are important regulators of cell function. Those ions also may interact and it is important, therefore, to measure their concentrations simultaneously. In the present studies we used a system developed for that purpose, a fluorescent emission ratio technique for simultaneous analysis of calcium (Indo-1) and pH (SNARF-1) in single cells at video rates, and determined if arginine vasopressin (AVP, 12.5 mumol/l) evoked [Ca2+]i and pHi signals interact in MDCK cells. We also employed a simple system for analysing the side specific (basolateral or apical) application of agonist to polarized cell layers on permeable membranes. AVP is found to evoke simultaneous changes in both pHi and [Ca2+]i. Basolateral application induced transient acidification, followed by partial recovery, and a [Ca2+]i transient with kinetic pattern similar to that of the pHi. Apical application also caused a mirror image pHi and [Ca2+]i pattern but of smaller magnitude (no peak). Selective removal of extracellular calcium ([Ca2+]e) or sodium ([Na+]e) dissociated the pHi and [Ca2+]i responses in both cases. Na+e removal abolished the pHi changes, but not the [Ca2+]i transients. [Ca2+]e removal abolished the [Ca2+]i changes and reduced, but did not abolish, the pHi responses. Thus, AVP induces pHi changes which are modified by calcium while calcium signalling is not modified by changes in pHi.

Animals↗
PubMed1995

Maintenance of bradykinin-induced intracellular calcium response of MDCK cells depends on extracellular calcium.

Bradykinin (BK) induces intracellular calcium ([Ca2+]i) release in Madin-Darby canine kidney (MDCK) cells. During long-term continuous BK exposure, cells become desensitized and fail to respond to a new BK stimulus. We used a protocol of repeated short-term BK addition and removal. MDCK cells were loaded with the Ca-indicator indo-1 and were exposed to BK (100 nmol/L) for 10 seconds, followed by BK removal. This cycle was repeated four to eight times while [Ca2+]i was continuously recorded. In a Ca-free bath, the cells gradually became completely desensitized to repeated BK stimuli. In the presence of 1 mmol/L or 10 mmol/L Cae, however, repeated addition of BK caused repeated [Ca2+]i transients with partial decrease of peak heights (327 and 436 nmol/L delta[Ca2+]i final) (partial desensitization). Repeated BK stimuli also led to partial desensitization (70% to 85%) to adenosine triphosphatase and carbachol (heterologous desensitization). BK also reduced peak thapsigargin response (70%), consistent with partial depletion of endoplasmic reticulum Ca pools. Our results show that MDCK cells maintain their sensitivity to BK during repeated short-term BK exposures. Available Ca3 plays a major role in modulating the degree of cellular responsiveness.

Animals↗
PubMed1994

Renal protective effects of enalapril in hypertensive NIDDM: role of baseline albuminuria.

The primary results of a three-year prospective, double-blind, placebo-controlled trial in non-insulin-dependent diabetic (NIDDM) patients show that an anti-hypertensive regimen, which includes the ACE inhibitor enalapril, preserves renal function to a greater extent than therapy with antihypertensive agents excluding ACE inhibitors (J Am Soc Nephrol 3:335, 1992). The influence of baseline urinary albumin excretion on the renal protective effects of enalapril treatment in these subjects was the objective of this further analysis. Adequate data were available in 121 patients of the 165 hypertensive NIDDM individuals studied [baseline glomerular filtration rate (GFR) 30 to 100 ml/min/1.73 m2]. Twenty-four hour urinary excretion of albumin (UAE), protein, urea nitrogen, creatinine and isotopically determined GFR were measured at baseline and six month intervals. Glycemic control and blood pressure regulation were assessed every three months. The rate of loss of GFR was significantly greater in patients with overt proteinuria at baseline (UAE > 300 mg/24 hr) as compared to patients with baseline sub-clinical proteinuria (UAE < or = 300 mg/24 hr). Antihypertensive treatment with enalapril preserved GFR significantly better (P < 0.01) in the patients with sub-clinical proteinuria at baseline (UAE < or = 300 mg/24 hr) than other antihypertensive treatments which excluded the ACE inhibitor. Furthermore, only 7% of the enalapril-treated group progressed to clinical albuminuria compared to 21% of control treated patients. Although the enalapril-treated group had a lower mean blood pressure during the maintenance period, no correlation between blood pressure (systolic, diastolic or mean arterial) and rate of change of GFR was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Simultaneous imaging of intracellular [Ca2+] and pH in single MDCK and glomerular epithelial cells.

The interrelationships between changes in intracellular calcium concentration ([Ca2+]i) and intracellular pH in Madin-Darby canine kidney cells and kidney glomerular epithelial cells exposed to various stimuli were analyzed simultaneously using a new design of a fluorescence video microscope. Cells were double labeled with indo 1 and SNARF 1 dyes and were excited simultaneously at 350 and 540 nm. Images at four emission wavelengths were captured simultaneously at 405, 475, 575, and 640 nm at 30 frames/s for the two ratio dyes. SNARF sensitivity to pH between 6.5 and 8.0 was unchanged by [Ca2+]i. The SNARF ratio maps were used to correct the pH-dependent changes in the calculation of local cell calcium. NH4Cl loading produced the expected alkalinization and a concurrent rise in [Ca2+]i. When the NH4Cl was removed and the cells became acidic, a second rise in [Ca2+]i was recorded. Both changes in [Ca2+]i were from intracellular stores since they persisted in the absence of extracellular calcium. The findings demonstrate the need for pH correction of indo 1 recordings.

Ammonium Chloride↗
PubMed1993

Calcium regulation of intracellular pH in pituitary intermediate lobe melanotropes.

The regulatory activities of both intracellular calcium ([Ca2+]i) and intracellular pH (pHi) have greatly increased interest in the study of their interdependence. We have designed an epifluorescence video microscope that will image the fluorescence from two ratio dyes, indo-1 (for [Ca2+]i) and SNARF-1 (for pHi) at video rates. We examined primary cultures of pituitary intermediate lobe melanotropes loaded with both dyes. After experimentation, cells were positively identified by fluorescence immunohistochemistry. K(+)-induced depolarization of melanotropes produced increases in [Ca2+]i due to activation of L-type Ca channels. A secondary Ca2+ peak or oscillations were often seen. After treatment with carbonyl cyanide m-chlorophenylhydrozone, depolarization produced a rise in intracellular [Ca2+]i as well as oscillations. After thapsigargin or cyclopiazonic acid treatment, depolarization produced a primary Ca2+ elevation, but the secondary Ca2+ changes disappeared. This suggests that the oscillations were due to Ca2+ release from an endoplasmic reticulum type of intracellular store. All of these increases in [Ca2+]i were also directly coupled to a rise in intracellular H+. The close association between intracellular Ca2+ and H+ suggests that the observed pHi changes were due to the release of H+ upon binding of Ca2+ to intracellular buffers. This direct obligate coupling of intracellular Ca2+ and H+ suggests the possibility that pH-dependent cellular processes are directly activated by sudden increases in intracellular Ca2+ levels. This second messenger type of signaling system would be activated whether the Ca2+ was released from intracellular stores or entered the cell via plasma membrane Ca2+ channels.

Animals↗
PubMed1992

The role of disease duration and hypertension in albumin excretion of type I diabetes mellitus.

The objective of this study was to examine the relationship between blood pressure, albumin excretion, and renal function in patients with type I diabetes mellitus. The study design was as follows: nonselected consecutive patients with type I diabetes mellitus were divided into three groups by level of albumin excretion rate (AER): less than 20 micrograms/min, 20 to 200 micrograms/min, and greater than 200 micrograms/min. The setting for the study was an outpatient diabetic clinic in a tertiary referral center. There were 166 patients studied: 53% men, 47% women, 86% white, 17% treated for hypertension. Seventy-six percent had an AER less than 20 micrograms/min, 18% had an AER of 20 to 200 micrograms/min, and 6% had an AER of greater than 200 micrograms/min. Glycosylated hemoglobin did not differ between groups. AER was increased with age and disease duration (P less than 0.005 by analysis of variance) after 10 yr of disease. Serum creatinine (P less than 0.005) and systolic (P less than 0.005) and diastolic (P less than 0.01) blood pressures were also increased with AER. Serum creatinine and blood pressure were found to be increased in parallel after 10 yr of disease, but both remained within the normal range overall. A comparison of individual blood pressures in patients not taking antihypertensive drugs (N = 138) with age-related blood pressures of nondiabetic subjects revealed increased systolic and diastolic blood pressures at all ages. Group comparison demonstrated a significant link between increased AER and serum creatinine (declining renal function) and increased blood pressure after a latent period of 10 yr. Blood pressure appears to be increased from the earliest age in diabetes compared with healthy populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Vasoactive substances induce cytoskeletal changes in cultured rat glomerular epithelial cells.

Angiotensin II (ANG II), atrial natriuretic peptide III (ANP), and sodium nitroprusside (SNP) alter capillary hydraulic conductivity in isolated glomeruli. These agents also affect cyclic nucleotide levels of glomerular epithelial cells (GEC). ANG II increases cAMP, whereas ANP and SNP increase cGMP. The effects of these vasoactive substances on GEC cytoskeleton were tested by incubating cells from primary cultures or an established cell line with each agent. Changes in the cytoskeleton were assessed by staining for F-actin with Bodipy phallacidin and for tubulin with NBD-colcemid. Control cells exhibited short bundles of F-actin or stress fibers near the base of the cells. These were frequently arranged in parallel and occasionally appeared to radiate from the center of the cell. Microtubules were arranged in a fine network throughout the cell with increased density adjacent to the nucleus and within the nucleolus. Incubation of GEC with 10(-7) M ANG II, cholera toxin, or 8Br-cAMP for 2 at 37 degrees C resulted in rearrangement of F-actin into distinct stellate patterns with a decrease in the relative intensity of the peripheral staining, all concurrent with a fivefold increase in intracellular cAMP. The incubation of GEC with 10(-6) M ANP or 10(-7) M SNP for 2 h at 37 degrees C resulted in apparent disassembly of stress fibers, sparse and more diffuse fluorescence, and some increase of fluorescence at the periphery of the cells, all concurrent with a 10-fold increase in intracellular cGMP. Cytochalasin D incubation led to complete disassembly of actin filaments.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗
PubMed1992

Effect of angiotensin-converting enzyme inhibition on renal function and albuminuria in normotensive type I diabetic patients.

Normotensive patients with insulin-dependent (type I) diabetes mellitus (n = 18) were given 25 mg captopril (b.i.d.) and placebo for 3 mo in a randomized double-blind crossover study. Patients had normal renal function, and none had retinopathy. Albuminuria was less than 20 micrograms/min in 12 patients and between 20 and 200 micrograms/min in the other 6. Patients were examined at the end of the placebo and captopril phases. Captopril caused little reduction in blood pressure obtained by 24-h ambulatory monitoring (systolic 126.0 +/- 2.7 to 123.9 +/- 2.4 mmHg, P less than 0.08; diastolic 74.2 +/- 1.9 to 72.1 +/- 1.9 mmHg, P less than 0.09). Captopril lowered glomerular filtration rate from 99.5 +/- 7.7 to 71.0 +/- 5.5 ml.min-1. 1.73 m-2 (P less than 0.01), whereas renal plasma flow (443.9 +/- 15.2 ml.min-1. 1.73 m-2) remained unchanged. Filtration fraction was reduced from 22.4 +/- 1.4 to 17.4 +/- 1.4% (P less than 0.01). Urinary albumin excretion was reduced from 59.1 +/- 0.15 to 27.7 +/- 13.9 micrograms/min (P less than 0.1). Reduction was related to the extent of initial albuminuria (r = 0.997, P less than 0.001), a relationship that remained significant after logarithmic transformation (r = 0.540, P less than 0.02). Dextran clearance was used to determine glomerular capillary function. Angiotensin inhibition caused reduction in effective glomerular pore size and also reduced flow via the nondiscriminatory shunt. Angiotensin inhibition in normotensive patients with type I diabetes was well tolerated. Reduction in albuminuria is mediated by a combination of hemodynamic changes and alterations in glomerular capillary function.

Adult↗
PubMed1992

Ambulatory blood pressure in type I diabetes mellitus. Comparison to presence of incipient nephropathy in adolescents and young adults.

AMBP measurements were obtained at 20-min intervals during the day and at 60-min intervals during the night in 38 adolescents and young adults (12-25 yr old) with type I diabetes, and in 36 healthy, nondiabetic control subjects of comparable age. The group of patients with elevated AER (greater than 15 micrograms/min) had higher mean 24-h sBP, dBP, and BPB (defined as the prevalence of systolic readings greater than 130 mm Hg or diastolic readings greater than 85 mm Hg) compared with both the group of patients with type I diabetes and AER less than 15, and the control group. The normal diurnal variation in BP and BPB was observed in the control group and the group with type I diabetes and AER less than 15, whereas the nocturnal decrease observed in the group with type I diabetes and AER greater than 15 was not statistically significant. Elevations in AMBP of the patient group with AER greater than 15 were reflected in random BP measurements. Even though the mean random BP measurements of all groups were within the normal range for age, the mean random sBP and dBP of the type I diabetes patients with AER greater than 15 was higher than both the control group and the group with type I diabetes and AER less than 15. The GFR, determined by the clearance of 99Tc-DTPA, was associated negatively with measures of AMBP and AER in the group with AER greater than 15.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Diminished glomerular capillary hydraulic conductivity precedes morphologic changes in experimental diabetes mellitus in the rat.

Glomerular ultrafiltration coefficient, Kf, is diminished in established diabetic nephropathy. To determine whether Kf is decreased because of a decrease in capillary area, A, and or in hydraulic conductivity, Lp, glomerular Kf and morphometric parameters were measured, and Lp was calculated in glomeruli of young rats with STZ-induced DM and in control rats. STZ was administered to Fischer 344 rats that weighted 50-75 g; glomeruli were examined after 3 or 5 mo of DM, and their structure and function was compared with that of control rats. The effects of insulin or of an ACEI, enalapril, also were assessed after 3 or 5 mo. Growth of DM rats was markedly impaired, and their ratio of kidney weight to body weight was increased. Ccr was proportional to rat weight, and the ratio of Ccr to body weight was not different in DM and control rats. At 3 mo, average volume of glomeruli isolated from DM rats was less than that of glomeruli from control rats. In contrast, glomerular volume after 5 mo was equal in DM and control rats. No increase in GBM thickness or mesangial volume was observed, nor was any decrease seen in GBM area in DM rats at 5 mo. Kf was lower in DM rats than controls after 3 mo, but not after 5 mo. The Lp of DM and control glomeruli did not differ at 3 mo, but was lower in DM at 5 mo. Insulin therapy improved somatic growth and increased kidney and glomerular size in DM rats; the kidney weight/body weight ratio remained elevated.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Single-dose subcutaneous iodine-131-iodohippurate for determination of renal plasma flow.

Subcutaneous administration of a single dose of 131I-iodohippurate was used for determination of renal plasma flow (RPF) in 20 subjects during water diuresis. Slow release of tracer (200 microCi) permitted serial clearance measurements over 5 hr that were compared to standard, constant infusion, PAH clearance (mean 379.5 +/- 34.9 ml/min/1.73 m2, range 50.9 to 696.3 ml/min/1.73 m2). RPF(Isotope) was 424.9 +/- 30.3 ml/min/1.73 m2 (range 144.4 to 746.5 ml/min/1.73 m2) and highly correlated with RPFPAH (r = 0.883, p less than 0.0001). This technique permits prolonged studies of renal plasma flow under steady-state conditions without constant infusion.

Adult↗
PubMed1990

Principles, uses, and complications of hemodialysis.

Hemodialysis replaces missing renal function, and it does so incompletely. Current technology provides for reliable and flexible treatment strategies guided by patient's well-being and careful evaluation of plasma urea concentrations. Hemodialysis is indicated in many medical emergencies, notably fluid overload and hyperkalemia, and all types of renal failure. Hemodialysis requires a sizable effort and a significant commitment of time by both patients and professionals and is not suited for every patient with renal insufficiency. Notable treatment-related side effects include cramps, hypotension, problems with blood access, and reactions to dialyzer membrane materials. Far from treating underlying disease, hemodialysis extends life and permits the expression of much progressive multisystem disease. Cardiovascular disease is the most common comorbid condition and cause of early mortality.

Anaphylaxis↗
PubMed1990

Controlled changes in chronic dietary protein intake do not change glomerular filtration rate.

The effect on renal function (creatinine clearance [Ccreat] and inulin clearance [Cinulin]) of changes in chronic dietary protein intake was studied in seven healthy male subjects. Serial 24-hour urine collections were used to determine creatinine excretion (UcreatV) and Ccreat. Subjects were examined after ad libitum (ad lib) food intake and after 2-week periods of high protein diet ([HPD] 1.6 g/kg body weight [BW] per day) and low protein diet ([LPD] 0.5 g/kg BW per day). Inulin clearance (Cinulin) was determined at the end of each 2-week diet period. UcreatV increased from 1,838.8 +/- 97.2 mumol/kg (20.8 +/- 1.1 mg/kg) BW to 2,068.6 +/- 106.1 mumol/kg (23.4 +/- 1.2 mg/kg) BW daily during HPD and decreased significantly to 1,555.9 +/- 167.9 mumol/kg BW per day (17.6 +/- 1.9 mg/kg BW per day) with beginning of LPD. Ccreat rose from 1.54 +/- 0.09 mL/s 1.73 m2 (92.5 +/- 5.5 mL/s.1.73 m2 (104.7 +/- 4.9 mL/min/1.73 m2) during HPD and decreased to 1.23 +/- 0.04 mL/s.1.73 m2 (74.0 +/- 2.2 mL/min/1.73 m2) with initiation of LPD. There was no difference between Cinulin after HPD (1.42 +/- 0.12 mL/s.1.73 m2; 84.9 +/- 7.2 mL/min/1.73 m2) and after LPD (1.36 +/- 0.05 mL/s.1.73 m2; 81.4 +/- 2.9 mL/min/1.73 m2). This study confirms the effect of protein intake on Ccreat and UcreatV, but fails to show an effect of changes in chronic protein intake on glomerular filtration rate (GFR). Ccreat during dietary protein restriction to 0.5 g/kg/d is similar to Cinulin and may be a useful measure of GFR under circumstances where more specific inulin or isotope studies are not available.

Adult↗
PubMed1990

In vitro effects of cyclosporine on glomerular function.

Cyclosporine A (CsA) causes vasoconstriction and decrease in glomerular filtration rate. Experiments were conducted in isolated glomeruli to study effects of CsA of glomerular perfusion and independent of systemic or renal factors. CsA caused a dose dependent decrease in glomerular volume consistent with mesangial contraction. The ultrafiltration coefficient Kf was significantly lower after incubation in 4 X 10(-4) M CsA when compared to control (2.81 +/- 0.2 vs 5.19 +/- 0.5 nl/min X mm Hg; p less than 0.001). Hydraulic conductivity Lp was diminished by CsA from 2.69 +/- 0.11 to 1.41 +/- 0.05 microliter/min X mm Hg X cm2 (p less than 0.001). These findings demonstrate a direct effect of CsA on the glomerulus which must be considered in addition to drug-induced changes in perfusion and tubular function.

Animals↗
PubMed1990

Glomerular effects of angiotensin II require intrarenal factors.

Glomerular ultrafiltration coefficient (Kf) of glomeruli isolated from kidneys of normovolemic rats decreases following infusion of angiotensin II (ANG II). Kf from isolated glomeruli after ANG II infusion in vivo and from isolated perfused kidneys following infusion of ANG II in vitro was measured to determine whether the decrease required the presence of systemic factors. Filtration was induced in vitro and the maximum rate of change in glomerular volume was used to calculate Kf. Glomerular capillary hydraulic conductivity (Lp) was calculated from Lp = Kf/A where the basement membrane area A was calculated as 3 X pi X D2. ANG II infusion in vivo in rats diminished Lp from 3.19 +/- 0.19 to 1.96 +/- 0.13 and to 1.82 +/- 0.11 microliters.min-1.mmHg-1.cm-2, respectively. ANG II infusion into isolated kidneys caused a similar decrease in Lp (3.55 +/- 0.11 to 2.37 +/- 0.07). ANG II infusion either in vivo or during isolated kidney perfusion decreases Kf and Lp. ANG II effects do not require the presence of extrarenal factors but depend on perfusion in situ since incubation of isolated glomeruli with ANG II did not alter Kf.

Angiotensin II↗