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Biomedical subjects

T Wiegmann

Publications and source records attributed to T Wiegmann.

11 recordsLinked to original sources
PubMed1999

Iron uptake promotes hyperoxic injury to alveolar macrophages.

Iron uptake by cells may increase the intracellular pool of prooxidant iron prior to storage of iron within ferritin. Because hyperoxia is toxic to alveolar macrophages (AM) via mechanisms involving oxidant stress, we hypothesized that iron uptake by AM might promote hyperoxia-induced injury. To assess this hypothesis, we cultured AM recovered from healthy volunteers under conditions of normoxia or hyperoxia (60% or 95% oxygen) in media of varying iron content, including control media (3 microM iron) and media supplemented with iron (FeCl3; total iron 10, 20, or 40 microM). AM injury was assessed by measuring release of lactate dehydrogenase (LDH), phagocytic activity for yeast, and cytosolic concentrations of calcium ([Ca2+]i) as determined by ratio image analysis of AM loaded with the fluorescent calcium probe indo-1. There was dose-dependent accumulation of iron and ferritin synthesis in AM exposed to iron-supplemented media. Exposure of AM to hyperoxia (60% and 95% oxygen, 18 h) in control media increased LDH release and impaired phagocytic activity for yeast; however, similar hyperoxic exposures in iron-supplemented media significantly increased the cells' LDH release and decreased phagocytosis. Exposure to 95% oxygen increased the [Ca2+]i of AM over 18 h, but similar exposure in iron-supplemented media induced greater increases in [Ca2+]i. As compared with exposure to normoxia, exposure to hyperoxia (60% and 95% oxygen) also decreased iron uptake and, to a greater extent, ferritin synthesis by AM in iron-supplemented media. These data suggest that: (1) iron uptake promotes hyperoxic injury to AM; and (2) hyperoxia impairs the capacity of AM to sequester iron in ferritin.

Bronchoalveolar Lavage Fluid↗
PubMed1998

Calcium mobilization and protease-activated receptor cleavage after thrombin stimulation in motor neurons.

Thrombin, the ultimate enzyme in the blood coagulation cascade, has prominent actions on various cells, including neurons. As in platelets, thrombin increases [Ca2+]i mobilization in neurons, and also retracts neurites. Both these effects are mediated through a G protein-coupled, proteolytically activated receptor for thrombin (PAR-1). Prolonged exposure to thrombin kills neurons via apoptosis, that may also involve PAR-1 activation. Increased [Ca2+]i has been a unifying mechanism proposed for cell death in several neurodegenerative diseases. Thrombin-elevated calcium levels may activate intracellular cascades in neurons leading to cell death. Since thrombin mediates its diverse effects on cells through both heterotrimeric and monomeric G proteins, we also explored what effect altering differential G protein coupling would have on the neuronal response to thrombin. We studied calcium mobilization by thrombin in a model motor neuronal cell line, NSC19, using fluorescence image analysis. Confirming effects in other neuronal types, thrombin caused dramatic increases in [Ca2+]i levels, both transiently and after prolonged exposure, which involved activation and cleavage of the PAR-1 receptor. Using enzyme linked immunosorbent assay (ELISA) and dot-blot analysis, we found that the N-terminal fragment of PAR-1 was released into the medium after exposure to thrombin. We confirmed that PAR-1 protein and mRNA expression occurred in motor neurons. We found that cholera toxin inhibited thrombin-mediated Ca2+ influx, pertussis toxin did not significantly alter thrombin action, and lovastatin, a small 21-kDa Ras GTPase (Rho) modulator, showed a tendency to reduce the thrombin effect. These data indicate that thrombin-increased [Ca2+]i, sufficient to trigger cell death in motor neurons, might be approached in vivo by modulating thrombin signaling through PAR-1.

Animals↗
PubMed1993

Cigarette-smoking affects platelets and endothelium in chronic hemodialysis patients.

Previous work has shown that cigarette-smoking affects platelets and endothelium in men and women without renal failure. The present study compared 10 male habitual smokers receiving maintenance hemodialysis for chronic renal failure with 11 healthy male habitual smokers before and after controlled cigarette-smoking after a 12-hour period of abstinence. Collagen-induced platelet aggregation was not significantly different in the two groups of men before smoking. The platelet aggregate ratio was lower and the plasma concentration of platelet factor 4 was higher in the dialysis patients than in the healthy men (p < 0.05). Mean or median values before and after cigarette smoking by the dialysis patients were 42 and 62 chart units for collagen-induced platelet aggregation, 0.88 and 0.77 for the platelet aggregate ratio, 6.2 and 8.5 ng/ml for the plasma concentration of platelet factor 4, 0.8 and 1.7 per counting chamber for the endothelial cell count and 4 and 37 ng/ml for the plasma nicotine concentration (each p < 0.01). None of the changes which occurred in the dialysis patients was statistically significantly different from those in the healthy men. We conclude that cigarette-smoking has similar effects on platelets and endothelium in patients receiving maintenance hemodialysis and in healthy controls.

Adult↗
PubMed1990

Correlation of urinary albumin and beta-2-microglobulin and growth hormone excretion in patients with diabetes mellitus and short stature.

We examined the correlation between urinary GH, urinary albumin, and beta-2-microglobulin excretion to determine how the excretion of GH relates to markers of renal glomerular and tubular function. Urinary albumin and GH excretion was determined in timed daytime and nighttime urine collections obtained from both subjects with diabetes mellitus and subjects with short stature. For subjects with diabetes, urinary GH excretion rate correlated highly with urinary albumin concentration and excretion rate in both the range of 0 to 1.6 g/L (r = 0.75), P less than 0.001) and in the microalbuminuria range, 0 to 0.4 g/L (r = 0.53, P less than 0.001). Changes in GH and albumin excretion occurred in parallel in 71% of the subjects with diabetes and elevated albumin excretion. The mean GH excretion rate was higher in the group with elevated albumin excretion rate (AER) during both day and night compared to the group with microalbuminuria during the day and normal AER at night. For subjects with short stature, the mean albumin excretion rate was 0.7 +/- 1.3 micrograms/min (range 0.05-8.3 micrograms/min) using a sensitive enzyme-linked immunosorbent assay to measure albumin concentration. The correlation of GH and albumin excretion rates for the subjects with short stature was not statistically significant (r = 0.14, P less than 0.5). About half of the subjects with diabetes and elevated AER (greater than 10 micrograms/min) had a GH excretion rate within the range observed in subjects with short stature. The GH and albumin excretion rate were not correlated in this group. There was a positive correlation of both albumin and GH excretion rate with age in the subjects with diabetes. Urinary GH and beta-2-microglobulin excretion rates were determined in a larger group of subjects with diabetes and a separate group with short stature. Urinary GH and beta-2-microglobulin excretion were correlated both in subjects with diabetes (r = 0.46, P less than 0.001) and with short stature (r = 0.64, P less than 0.001). The association was present in urine collected either during the day or night. The mean GH excretion rate of the group with diabetes was greater than the group with short stature. In conclusion, there was an association of urinary GH and albumin excretion rate in subjects with abnormal glomerular function as indicated by elevated albumin excretion rate. An association of urinary GH and beta-2-microglobulin excretion was observed in subjects with normal tubular function.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1977

Hypomagnesemic hypocalcemia. Early serum calcium and late parathyroid hormone increase with magnesium therapy.

A patient with short-bowel syndrome developed severe hypomagnesemia (0.2 mEq/liter) associated with symptomatic hypocalcemia (6.1 mg/100 ml). Parathyroid hormone (PTH) levels were normal but inappropriately low. During therapy with magnesium sulfate, an initial hypocalcemia was followed by a calcemic response without a change in PTH levels. This indicates improved bone responsiveness to circulating low levels of endogenous PTH with magnesium replenishment, which appears to be related to the restoration of magnesium-dependent cellular mechanisms. The additional observation of a slow and delayed increase in PTH, despite normal calcium levels, indicates improvement of hormone synthesis.

Calcium↗
PubMed1977

Technetium-99m-pyrophosphate bone scans in hyperparathyroidism.

Most patients with primary hyperparathyroidism have normal 5-hr bone-to-soft-tissue ratios for 99MTc-pyrophosphate. In contrast, all five patients with advanced secondary hyperparathyroidism in this study showed significant (p less than 0.001) increases of bone uptake. In the early period after parathyroidectomy, there was no quantitative or qualitative change in uptake. A limited decrease of bone uptake was observed only after prolonged periods of observation. In itself, parathyroid activity seems to have little direct influence on bone uptake of 99MTc-pyrophosphate.

Adolescent↗
PubMed1976

Right-sided endocarditis and ventricular septal defect.

Right-sided endocarditis occurred in a 40-year-old woman with ventricular septal defect. This association is uncommon in adults. Because of the changing and variable clinical patterns of this disease, it is difficult to make a prompt diagnosis. In this case diagnosis was delayed for almost a year. The occurrence of pneumonia due to Streptococcus viridans was the most important extracardiac manifestation.

Adult↗
PubMed1976

Relationship between bone uptake of 99mTc-pyrophosphate and hydroxyproline in blood and urine.

In a group of hospital patients with various diseases, the urinary hydroxyproline-to-creatinine ratio showed a significant correlation (r = 0.63; p less than 0.001) with the 5-hr bone-to-soft-tissue ratio for 99mTc-pyrophosphate uptake. In patients on chronic hemodialysis, a similar correlation was found between the 5-hr bone-to-soft-tissue ratio and hydroxyproline levels in plasma and serum. The findings suggest that 99mTc-pyrophosphate binding by bone is related to collagen metabolism.

Aged↗
PubMed1976

Abnormal 99mTechnetium-tin-pyrophosphate bone scans in chronic renal failure.

A high incidence of abnormal 99mTechnetium-tin-pyrophosphate (99mTcPPi) is reported in a population of chronic renal failure patients. Using the 5 hour bone to soft tissue ratio as a quantitative index of increased uptake, 78% of 45 long-term dialysis patients and a similar proportion of non-dialyzed chronic renal failure patients were found to have increased uptakes. In animal studies using a uremic model, similar increased uptakes of 99mTcPPi was found with evidence of increased vascularity as reflected by red cell or plasma volumes in the bone or by the uptake of concomitantly administered 45Ca. The evidence suggests that the abnormal bone scans reflect abnormalities in collagen metabolism that occurs in the uremic state and that 99mTcPPi scans are useful in the diagnosis and management of renal osteodystrophy.

Animals↗