PubMed Health⌕ Search

Biomedical subjects

T Günther

Publications and source records attributed to T Günther.

At least 91 records · Page 5Linked to original sources

Extra-abdominal aggressive fibromatosis after treatment of a Morbus Hodgkin. A case report.

The proliferations of the connective tissue, which are summed up under the term fibromatoses, assume a special position with regard to their biologic behavior. While superficial fibromatoses are more likely to grow slowly, musculoaponeurotic fibromatoses (Desmoid tumor)--like malignant tumors--show a locally bound aggressive, rapid growth behavior. A metastazation, however, can never be proved. The research on etiology of fibromatoses has yielded only little knowledge. Besides genetic and hormonal factors, physical reasons are under discussion, too. The present study aims to add another description of a case report to the small number of case presentations on radiotherapy-associated fibromatosis. In 1977, a now 67-old-patient was irradiated because of a Morbus Hodgkin lymphoma in the left side of his neck. Prior to the radiation, the patient had undergone several surgeries. 17 years after the radiation, the patient developed an aggressive fibromatosis (prelaryngeal, right) in the formerly irradiated region. As the localization of the fibromatosis does not allow us to establish a connection to his numerous operations preceding the fibromatosis, a radiation-associated Desmoid tumor must be assumed. Immunohistologically, no estrogen receptors were detectable.

Actins↗

Buffering and activity coefficient of intracellular free magnesium concentration in human erythrocytes.

Human erythrocytes either untreated or Mg2+(-)loaded by means of A23187 in the presence of 3 or 12 mM MgCl2 were haemolysed by freezing and thawing. In the haemolysates the concentration of total Mg2+ (by atomic absorption spectrophotometry), free Mg2+ (by a Mg2+(-)sensitive electrode) and ATP were determined. The increase in the free Mg2+ concentration was also measured when titrating the haemolysates with MgCl2. The experiments yielded a total Mg2+ buffer capacity of 4.85mM with a Ka of 0.9 mM-1, indicating that 2,3 bisphosphoglycerate was the main Mg2+ buffer in haemolysates of erythrocytes which had been ATP-depleted during preparation. The activity coefficient of free Mg2+ in erythrocytes was the same as in the chloride-based calibration solutions.

Buffers↗

Interactions of polyamines in the measurement of free magnesium concentration by mag-fura-2 and 31P-NMR.

Polyamines, particularly spermine, in physiological concentrations interact with mag-fura-2 and the mag-fura-2/Mg2+ complex, resulting in reduced values of free Mg2+ concentration. Similarly, polyamines interact with ATP and MgATP. Thus, free Mg2+ concentration, as measured by 31P-NMR or mag-fura-2, is underestimated in the presence of polyamines, particularly of spermine.

Adenosine Triphosphate↗

Open brain, a new mouse mutant with severe neural tube defects, shows altered gene expression patterns in the developing spinal cord.

We describe a new mouse mutation, designated open brain (opb), which results in severe defects in the developing neural tube. Homozygous opb embryos exhibited an exencephalic malformation involving the forebrain, midbrain and hindbrain regions. The primary defect of the exencephaly could be traced back to a failure to initiate neural tube closure at the midbrain-forebrain boundary. Severe malformations in the spinal cord and dorsal root ganglia were observed in the thoracic region. The spinal cord of opb mutant embryos exhibited an abnormal circular to oval shape and showed defects in both ventral and dorsal regions. In severely affected spinal cord regions, a dorsalmost region of cells negative for Wnt-3a, Msx-2, Pax-3 and Pax-6 gene expression was detected and dorsal expression of Pax-6 was increased. In ventral regions, the area of Shh and HNF-3 beta expression was enlarged and the future motor neuron horns appeared to be reduced in size. These observations indicate that opb embryos exhibit defects in the specification of cells along the dorsoventral axis of the developing spinal cord. Although small dorsal root ganglia were formed in opb mutants, their metameric organization was lost. In addition, defects in eye development and malformations in the axial skeleton and developing limbs were observed. The implications of these findings are discussed in the context of dorsoventral patterning of the developing neural tube and compared with known mouse mutants exhibiting similar defects.

Animals↗

Increased Na+/Mg2+ antiport in erythrocytes of patients with cystic fibrosis.

Na+/Mg2+ antiport and Na(+)-independent Mg2+ efflux were investigated in erythrocytes of 41 patients with cystic fibrosis and 26 controls. Na(+)-independent Mg2+ efflux was unchanged in cystic fibrosis, but a significantly increased activity of Na+/Mg2+ antiport was detected (control: 0.16 +/- 0.02, cystic fibrosis: 0.39 +/- 0.06, Mg2+ efflux, mmol/30 min x 1 cells, mean +/- SEM, p < 0.01). An increased activity of Na+/Mg2+ antiport was only found in patients with severe clinical symptoms. There was no correlation of the increased Na+/Mg2+ antiport to the dF508 genotype. In a patient with increased Na+/Mg2+ antiport, the capacity of this transport system was unchanged 14 weeks after double lung transplantation but reached control values after 53 weeks. The sweat of cystic fibrosis patients with severe clinical symptoms showed a significantly increased Mg2+ concentration (control (n = 12): 0.053 +/- 0.08, cystic fibrosis (n = 9): 0.123 +/- 0.016 mmol/l, mean +/- SEM, p < 0.001).

Adolescent↗

Magnesium metabolism in erythrocytes of patients with chronic renal failure and after renal transplantation.

Plasma and erythrocyte Mg2+ concentrations were found to be increased in 14 haemodialysis patients with chronic renal failure and in 7 chronic renal failure patients receiving chronic ambulatory peritoneal dialysis. The rate of Na+/Mg2+ antiport was significantly higher in haemodialysis patients, but not in chronic ambulatory peritoneal dialysis patients (control: 0.15 +/- 0.02, haemodialysis: 0.46 +/- 0.08, chronic ambulatory peritoneal dialysis: 0.21 +/- 0.06; Mg2+, mmol/30 min x 1 cells). High erythrocyte Mg2+ content in chronic renal failure results from the increased plasma Mg2+, which induces elevated Mg2+ uptake during haematopoiesis. An increased rate of Na+/Mg2+ antiport, which only performs Mg2+ efflux, leads to a relatively lower erythrocyte Mg2+ content in haemodialysis patients compared with chronic ambulatory peritoneal dialysis patients. The elevated Na+/Mg2+ antiport in erythrocytes from haemodialysis patients was almost normalised after haemodialysis. Incubation of normal erythrocytes with heat-inactivated plasma from haemodialysis patients led to a doubling of Na+/Mg2+ antiport, indicating the presence of a heat-stable, dialysable plasma factor. This factor does not accumulate in chronic ambulatory peritoneal dialysis patients. After renal transplantation all changed quantities of Mg2+ metabolism returned to normal.

Adult↗

Effect of oxygen free radicals on Mg2+ efflux from erythrocytes.

Hydrogen peroxide destroyed the Na+/Mg2+ antiport in Mg(2+)-loaded human and rat erythrocytes and increased the leakage of intracellular Mg2+ and K+. These effects are opposite to the increase of Na+/Mg2+ antiport and unchanged Na(+)-independent Mg2+ efflux from erythrocytes of patients with cystic fibrosis score 3. Thus, the increase of Na+/Mg2+ antiport in these patients is not caused by increased formation of free radicals.

Animals↗

Increase of streptozocin toxicity by magnesium deficiency in the diabetic rat model.

To study interactions between magnesium (Mg) and diabetes mellitus, female SD-rats weighing ca. 230 g were rendered Mg-deficient by offering a diet providing only 20% of the rat's requirement. After 14 days the animals were injected 75 mg streptozocin (STZ) per kg body weight intraperitoneally. Placebo-treated controls received the same diet, however their drinking-water was enriched with 20 mmol/l Mg as the magnesium-L-aspartate hydrochloride. Mg deficiency remarkably increased STZ-induced lethality from 3.8% to 61.1% on day 35. Pronounced hyperglycemia and necrosis of pancreatic beta cells also suggest an increased effect of STZ on the pancreas during Mg deficiency. The underlying mechanisms are discussed. Food consumption was decreased in Mg-deficient animals and steeply increased 7 days following STZ treatment. Similarly consumption of drinking-water also increased. Since diabetic rats lost body weight, relative and absolute Mg intake via food or drinking-water increased. In this way further Mg depletion of diabetic rats was prevented.

Animals↗

Na(+)- and anion-dependent Mg2+ influx in isolated hepatocytes.

Hepatocytes, which were Mg(2+)-depleted during isolation, took up Mg2+ during reincubation. Mg2+ uptake was dependent on the concentration of extracellular Mg2+, Na+, Cl-, bicarbonate and phosphate. Li+ and choline+ did not substitute for extracellular Na+ in Mg2+ influx. Mg2+ influx was maximal when all three anion species were present, and did not occur when these anions were replaced by gluconate. Bicarbonate, phosphate and Cl- could substitute for each other. Mg2+ uptake in hepatocytes was inhibited by p-chloromercuribenzene sulfonate, ouabain, gramicidin D, amiloride and verapamil. The results were explained by the assumption that net Mg2+ influx in hepatocytes is operating via electroneutral Na+, Mg2+/anion cotransport driven by the Na+ gradient. However, electrogenic Mg2+ uptake gated by extracellular Na+ and anions could not be excluded.

4-Chloromercuribenzenesulfonate↗

Metabolism of PAH by fungi and correlation with extracellular enzymatic activities.

The activity to metabolize the polycyclic aromatic hydrocarbons (PAH) phenanthrene, anthracene, pyrene, fluorene and fluoranthene by Trametes versicolor, Pleurotus ostreatus (white rot fungi), Laetiporus sulphureus, Daedaela quercina, Flamulina velutipes (brown rot fungi), Marasmiellus sp. (litter decaying fungus) and Penicillium sp. M 1 (isolated from a PAH contaminated soil sample) were compared. Screening methods for the presence of exoenzymes (peroxidases, polyphenoloxidases, "radical generating" enzymes) were evaluated for their use in screenings for fungi degrading PAH. Laetiporus sulphureus and Penicillium sp. M 1 cometabolize several PAH with rates comparable to white rot fungi. In most of the cases the patterns of extracellular peroxidases indicate the potential of fungi to degrade PAH.

Fungi↗

Mechanisms and regulation of Mg2+ efflux and Mg2+ influx.

Net Mg2+ efflux occurred in human, chicken and rat erythrocytes, rat thymocytes and HL60 cells when the concentration of intracellular free Mg2+ ([Mg2+]i) was experimentally increased and proceeded until the original cellular Mg2+ content was reached, indicating induction and regulation of net Mg2+ efflux by increased [Mg2+]i. Net Mg2+ efflux was performed by electroneutral Na+/Mg2+ antiport, driven by the extra-/intracellular Na+ gradient. Na+/Mg2+ antiport was irreversible, performing only net Mg2+ efflux. Na+/Mg2+ antiport was inhibited by amiloride, quinidine and imipramine. Besides increased [Mg2+]i, Na+/Mg2+ antiport in thymocytes was regulated by cAMP which induced a maximal rate of Na+/Mg2+ antiport. Net Mg2+ influx occurred when the cellular Mg2+ content was experimentally reduced and stopped when after reincubation in suitable media the original cellular Mg2+ content was reached, indicating regulation by [Mg2+]i via feedback inhibition. Net Mg2+ influx in isolated hepatocytes was dependent on extracellular Mg2+, Na+, Cl-, HCO3- and Pi. Net Mg2+ influx may operate via electroneutral Na+, Mg2+/anion cotransport, driven by the extra-/intracellular Na+ gradient. However, electrogenic Mg2+ influx gated by extracellular Na+ and anions cannot be excluded. Net Mg2+ influx was stimulated by cAMP and inhibited by amiloride and verapamil. Net Mg2+ efflux and net Mg2+ influx are separate and regulated pathways, establishing homeostasis of intracellular Mg2+.

Animals↗

Perinatal development of iron and antioxidant defence systems.

The time course of malondialdehyde (MDA), Fe, vitamin E, superoxide dismutase (Cu, Zn-SOD) and glutathione peroxidase (GSH-Px) was measured in serum, liver, kidney and heart from rats between day 17 of gestation and day 20 after birth. MDA was higher in fetal than maternal tissues and showed a transient increase after birth. The low maternal MDA levels were reached later than 3 weeks after birth. Fe was higher in fetal than in maternal serum and liver. Five days after birth Fe drastically dropped in these tissues. The antioxidant factors vitamin E, Cu, Zn-SOD and GSH-Px were low in fetal tissues and rose after birth. It is discussed whether lipid peroxidation is increased in fetal tissues because of less-developed antioxidant defence mechanisms.

Animals↗

Oral magnesium supplementation as prophylaxis for noise-induced hearing loss: results of a double blind field study.

The effect of oral Mg-supplementation as prophylaxis against noise-induced hearing loss was tested in a placebo-controlled double blind study involving 320 voluntary subjects during a 2-month period of military training. The hearing thresholds of all subjects were checked and only persons with normal hearing were accepted. Before and after the 2-month training, blood samples were collected and Mg was analysed in serum, erythrocytes and lymphocytes. Seven days after the last exposure to firearm noise, the audiograms of all test subjects were checked and permanent threshold shifts (PTS) were determined. The total group received a drink containing either 4g Mg granulate verum (6.7 mmol Mg aspartate) or placebo every working day during the 2-month training period. The primary source of noise exposure were firearms: 420 shots per person, mean peak level 164 dB(A). The recruits used ear plugs with a mean insertion loss of 25 dB. In both groups Mg-concentration in serum and in erythrocytes increased with time. Lymphocyte Mg increased in the Mg group only. In the placebo group the percentages of ears with PTS > 25 dB at 4 kHz/6 kHz and/or 8 kHz after exposure to firearm noise were twice as high as in the Mg group.

Administration, Oral↗

Extraaural effects of chronic noise exposure on blood pressure, microcirculation and electrolytes in rats: modulation by Mg2+.

Rats maintained on normal Mg-containing diets for 12 weeks (plasma Mg = 0.96 +/- 0.02 mmole) and subjected to 85 dB(A), 12 h per day for 8 weeks; 95 dB(A), 16 h per day for 4 weeks demonstrated significant elevation in systolic and diastolic arterial blood pressure (ABP); plasma Mg showed a 15% decrease whereas aortic and portal vein muscle exhibited slight reductions in Mg content and elevation in Ca. Moderate (plasma Mg = 0.67 +/- 0.03 mmole) and more severely (plasma Mg = 0.28 +/- 0.01 mmole) Mg deficient animals not subjected to audiogenic stress (AS) also exhibited significant elevations in systolic and diastolic ABP; vascular tissue Mg content decreased whereas Ca content rose. Animals subjected to combined Mg deficiency and AS for 12 weeks exhibited the greatest deficits in plasma and vascular muscle Mg and the greatest elevations in systolic and diastolic ABP; vascular tissue Ca contents also showed the greatest increases. In-situ measurements of mesenteric arterioles, venules and precapillary sphincters in the various subgroups revealed negative correlation between the lumen sizes of these microvessels and plasma Mg. Also, there was an inverse correlation between plasma Mg and ABP. Capillary blood flow transit times were decreased in relation to the degree of plasma Mg reduction. A quantitative rarefication of true capillaries per mesentery was observed. In addition, vascular reactivity of terminal arterioles to constrictor agents (norepinephrine, angiotensin II, Ba2+) was in relation to the plasma and vascular tissue deficit in [Mg]. Reactivity to the dilator agent, histamine, decreased in proportion to Mg deficit. A rationale for therapeutic intervention with Mg may evolve from these studies.

Animals↗

Isoproterenol-induced Mg2+ uptake in liver.

Isoproterenol increased the Mg2+ content of hepatocytes after injection into rats or after addition to collagenase-dispersed hepatocytes. cAMP also the increased cellular Mg2+ content of isolated hepatocytes. This effect was prevented by staurosporine. Phorbol ester had no effect on the Mg2+ content of isolated hepatocytes, and after injection of isoproterenol into rats, protein kinase C of liver was not affected. It was concluded that isoproterenol induced long-term Mg2+ influx via the activation of protein kinase A which can be inhibited by staurosporine.

Alkaloids↗

Activation of Na+/Mg2+ antiport in thymocytes by cAMP.

Mg2+ efflux from Mg(2+)-loaded rat thymocytes was stimulated by 0.1 mM dibutyryl cAMP (db cAMP). The activation of Mg2+ efflux by db cAMP was more expressed at lower Mg(2+)-loading. cAMP induced only a very small increase in the concentration of intracellular free Mg2+ which cannot explain the activation of Na+/Mg2+ antiport. From these results it was concluded that cAMP increases the affinity of the Na+/Mg2+ antiporter for intracellular Mg2+, probably by phosphorylation.

Animals↗

The pulsatile GH secretion in acromegaly: hypothalamic or pituitary origin?

OBJECTIVE: We studied the effects of different modes of octreotide therapy on the pulsatile pattern of GH release in an attempt to define better its regulation by growth hormone-releasing hormone (GHRH) and somatostatin and its effects on IGF-I plasma levels in acromegaly. DESIGN: In six acromegalic patients not cured by previous treatment we compared the 24-hour GH secretion profiles under basal conditions with subcutaneous (s.c.) bolus injections of 100 micrograms octreotide every 8 hours and with continuous s.c. infusions of the same daily dose. Blood samples were taken every 10 minutes over 24 hours followed by a GHRH test (100 micrograms GHRH i.v.) with blood sampling every 15 minutes for another 2 hours. After a 4-week interval all patients were treated either by the bolus or continuous mode of octreotide application in a randomized cross-over design. On day 4 of treatment blood sampling and GHRH test were repeated. Octreotide treatment was withdrawn for another 4 weeks; all patients then received the alternate application mode and were measured under similar conditions. MEASUREMENTS: Serum GH and plasma IGF-I concentrations were analysed by serial array averaging. IGF-I levels were measured in two different assays with and without previous protein extraction. For GH pulse detection three different algorithms (Cluster, Pulsar, Desade) were applied. RESULTS: With both treatments, the initially elevated basal 24-hour mean serum GH concentrations (58.0 +/- 9.7 mU/l mean +/- SEM) decreased significantly (bolus: 11.5 +/- 4.9 mU/l, P < 0.001 vs basal; continuous infusion: 7.6 +/- 1.9 mU/l, P < 0.001 vs basal) after 4 days. GH suppression was significantly more pronounced following continuous infusion than bolus (P < 0.05). IGF-I plasma concentrations were lowered significantly (P < 0.05) with both forms of treatment which did not differ between themselves. Bolus and continuous infusion treatment significantly inhibited (P < 0.05) the amplitudes of pulsatile GH release, but did not change the pulse frequency. In two of the patients, GHRH stimulation did not increase GH serum levels suggesting a constitutive activation of adenylyl cyclase. CONCLUSION: Continuous subcutaneous octreotide treatment in acromegaly suppresses mean GH levels better than bolus injection. The number of GH pulses remains unaffected by both modes of treatment providing evidence against a somatostatinergic mechanism of pulsatile GH secretion in these patients. The unchanged frequency of pulsatile GH release in the patients unresponsive to exogenous GHRH indicates that this pattern might be independent of hypothalamic GHRH and somatostatin and suggests a pituitary-derived mechanism for GH pulse generation in acromegaly.

Acromegaly↗