Prospective analysis of 10 different parameters of acute renal allograft rejection.
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Biomedical subjects
Publications and source records attributed to T Müller.
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Mouse brains were stained supravitally with methylene blue and studied in paraffin sections by light microscopy. In the perikarya, the dye was found to bind primarily to the nuclei; only slight staining of the cytoplasm was observed. Dye accumulations within nerve fibers were found in the nodes of Ranvier and in the varicosities of the unmyelinated endings. Specific dye binding in dendrites corresponded mainly to beads and spines. The accumulation sites in terminal neuronal processes appeared to be closely related to the plasma membrane. These morphological data would explain the neurophysiologically proven interaction of the dye with calcium-binding sites in membranes.
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99 patients affected with acute pancreatitis of different genesis were treated in hospital (necrotizing n = 38, mild form n = 61) from May 1990 to November 1991. Nearly 80% of these illnesses were ethanol-induced, 12% were of biliary origin. 90 patients were submitted to an adjuvant antioxidant therapy with selenium and D-alpha-tocopherol (necrotizing form n = 29, mild form n = 61). The average lethality rate of 34% (1982-1989) fell to 1.1% (1 female patient with biliarily induced pancreatitis). No lethal courses were observed in alcohol-induced, idiopathic, post-traumatic, and post-operative forms. Clinical courses proceeded more easily under adjuvant antioxidant therapy, surgical treatment was not necessary. A treatment at reasonable costs can be made in all general internal wards.
The in vitro DNA strand breaking activity of metallothionein (MT) containing Cd2+ and Zn2+ in a molar ratio of 5:2 is described. Studies with radical scavengers and electron paramagnetic resonance spectroscopy indicate that the DNA damage might be caused by a radical species formed by the native protein (i.e., MT) charged with the heavy metal ions. No DNA strand breaks are detectable with the heat-denatured MT or with Cd2+ or Zn2+ alone. Inhibition studies using EDTA as a metal ion chelator or N-ethylmaleimide to alkylate sulfhydryl groups suggest that both the bound heavy metal ions as well as the SH groups of the various cysteine residues of MT may be involved in the MT-dependent DNA cleavage. Further characterization showed that the DNA cleavage is more likely random than sequence- or base-specific. These observations may provide a clue in the search for initial events in Cd-related carcinogenicity.
Fluoxetine (FLX) is a selective serotonin (5-HT) reuptake inhibitor with therapeutic benefit in patients with obsessive-compulsive disorder (OCD). To evaluate the effect of chronic FLX treatment on 5-HT1A receptor responsivity, hypothermic, neuroendocrine, and behavioral responses to the selective 5-HT1A receptor ligand ipsapirone (IPS) were examined in patients with primary OCD. A single dose of 0.3 mg/kg of IPS or placebo were given under double-blind, random-assignment conditions to ten patients before and during FLX treatment. The ability of IPS to induce hypothermia and ACTH/cortisol release was significantly attenuated during chronic FLX as compared to the pretreatment IPS challenge. The behavioral effects of IPS, though minimal, were less pronounced during FLX treatment. While FLX was effective in reducing the severity of OC symptoms, no significant correlation between attenuation of 5-HT1A receptor-mediated functional measures and FLX-induced improvement in OC symptoms was detected. These findings are consistent with the development of adaptive hyporesponsivity of the 5-HT1A receptor-effector system complex possibly involving subsensitivity of the 5-HT1A receptor itself and/or decreased functional activity of the postreceptor signal transduction. Modulation of 5-HT1A receptor-effector system function may be critical to the antidepressant/anti-OC efficacy of 5-HT reuptake inhibitors.
The subcellular distribution of calcium in dermal melanocytes of Xenopus laevis and Poecilia reticulata has been analysed. Using two cytochemical methods, phosphate precipitation and a combined oxalate-pyroantimonate technique, electron energy-loss spectroscopy and electron spectroscopic imaging have been applied for elemental analysis. Both precipitation techniques revealed a high calcium content in the melanosomes of both species. Calcium was also located in the vicinity of collagen fibrils and in the plasma membrane.
Although the FGFs have been subject to extensive biological studies, only limited progress has been made so far in determining the critical elements of structure-activity relationships in the FGFs. Among the recognized structural elements with potential to affect the biological activity of FGFs are the cysteine residues, and the heparin- and receptor-binding domains. These features have been studied using a variety of experimental approaches, but the available data are inconclusive. For example, ambiguity regarding the presence of a disulfide structure in FGFs was not resolved until the availability of x-ray crystal structure data. Furthermore, the functionally important heparin- and receptor-binding domains have been poorly characterized, with some interpretations being controversial. In this report, we describe a novel fragment of basic FGF (bFGF) with high biological activity [Ser78,96-bFGF(70-153)]. This fragment was generated by pronase treatment of heparin-bound recombinant Glu3,5Ser78,96-bFGF mutant and is active in vitro at an ED50 of about 100 ng/ml. The structure of the fragment and the manner by which it was generated provide additional insight into important aspects of structure-activity relationships in FGFs. Specifically, we conclude that (a) the cysteines in our bFGF mutant do not form a disulfide bond, (b) the high-affinity heparin binding of bFGF critically depends on an intact 3-dimensional structure of the growth factor rather than on specific heparin-binding sequence domains, and (c) the bFGF sequence between residues 70 and 122 is important for high biological activity.
Besides complement, interleukin-1 and beta 2-microglobulin, activation of granulocyte function has been found out to be the major parameter in the determination of dialyzer biocompatibility. Unfortunately, the term 'granulocyte activation' has been widely used without restriction to distinct functions or definition of the related metabolic pathways. Therefore, the present study aims to elucidate the influence of hemodialysis (HD) pure membrane contact on granulocyte O2- release. The activation of this metabolic pathway which is also known as the so-called oxidative burst has been generally accepted as the initial signal in the granulocyte inflammatory activation cascade. Two membranes which have been previously shown to differ most widely in biocompatibility, cuprophane and polysulfone, have been selected. During HD with cuprophane the stimulatable O2- release was initially decreased, whereas polysulfone HD was effectless on granulocyte oxidative metabolism. The inhibition was due to a prestimulation of the granulocyte by pure interaction of the cell with the surface of the dialyzer membrane which could be proved by evaluating a plasma-free model. Activation of oxidative metabolism was strongly correlated with granulocyte adherence, showing a significantly higher rate of cell adherence in the case of cuprophane. Nevertheless, sheer forces were able to prevent granulocytes becoming adherent directly to the dialyzer membrane, but sheer forces were not able to influence the oxidative burst reaction, suggesting that the membrane-related stimulation of oxidative metabolism occurs immediately after a very short, possibly a single and hasty contact of the cell to the surface of the dialyzer membrane.
Blood membrane interaction during hemodialysis (HD) regularly leads to stimulation of leukocyte function and related release of granular enzymes. The present study aimed to investigate the possible influence of an HD-induced release of granulocyte elastase on blood coagulation. Therefore a highly sensitive substrate of polymorphonuclear elastase, the plasma coagulation factor XIII and its subunits A and S were determined in the course of HD. Consumption of both subunit A and S have been previously shown to be due to proteolysis by elastase, whereas a decrease in subunit A will be typical for thrombin activation. Furthermore, the thrombin-antithrombin III complex (TAT) acting as a predisposition parameter for thrombotic events was measured during HD treatment. Apart from a virtual fall in factor XIII total activity simulated by heparin, no significant HD-induced consumption of factor XIII could be observed. There was also no indication of an elastase- or thrombin-related change in subunit concentrations. Predialysis values of the TAT complex were generally elevated in HD patients, but only patients with acute renal failure showed a constant increase of TAT during HD. These findings suggest that HD patients are exposed to a latent activation of coagulation resulting in an elevated thrombogenetic risk mainly due to the underlying disease. An additional coagulatory stimulation by the HD procedure seems to be restricted to cases of acute renal failure.
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A heparin-binding protein with neurotrophic activity for perinatal rat neurons, termed HBNF, was purified to homogeneity from bovine brain utilizing pH 4.5 extraction, ammonium sulfate precipitation, cation exchange and heparin-Sepharose affinity chromatographies, and reverse phase HPLC. In the presence of protease inhibitors during extraction, a protein with an apparent molecular weight of 18 kDa was obtained in a yield of approximately 0.5 mg/kg brain tissue. The amino acid sequence of the first 114 residues of HBNF was determined and found to highly homologous to the cDNA-derived amino acid sequence of human HBNF, a 136-residue protein. Bovine and human HBNFs have identical molecular weights as judged by SDS gel electrophoresis and very similar amino acid compositions. This and overall sequence conservation suggest that bovine HBNF is also a 136 amino acid protein with a calculated molecular weight of approximately 15.5 kDa. The apparent discrepancy between calculated and observed molecular weights of bovine HBNF (and of human HBNF of which the complete sequence is known) is most likely a result of the highly basic nature of HBNF. If protease inhibitors were omitted during tissue extraction, two additional proteins with lower apparent molecular weights and identical N-terminal sequences were isolated, with the smallest forms being the major product. Amino acid analysis showed that the smaller forms correspond to C-terminally truncated HBNFs with calculated molecular weights of 13.6 and 12.4 kDa, lacking approximately 14 and 22 residues. Comparison of the HBNF protein sequence with sequences stored in the Protein Identification Resource/Genbank databases reveals high homology to the translation product of the MK-1 gene, which is retinoic acid-inducible in embryonic carcinoma cells and developmentally expressed during gestation in mice.
The use of OKT3 monoclonal antibodies has improved the immunosuppressive therapy. Due to the high efficiency of this treatment there is an increased risk of overimmunosuppression and occurrence of life-threatening viral infections. Therefore a cautious application of OKT3 is mandatory, a reliable differential diagnosis of the deteriorating graft function essential. In this study the high diagnostic value of urinary neopterin in the early and reliable diagnosis of CMV infection under OKT3 therapy in contrast to serum amyloid A as a marker of rejection could be shown. A differential therapy, supporting or reducing the immunosuppression, might be facilitated by daily monitoring of the neopterin and serum amyloid A.
In cases of urinary fistulae as well as lymphoceles the only ultrasound-guided percutaneous nephrostomy has led to a good result. In cases of ureterostenosis and distal fistulae the renal function could be preserved by percutaneous nephrostomy. The anterograde pyelography was exact in demonstrating localization of the stenosis which led to a better operative procedure. The interventional ultrasound therefore represents an important option in the treatment of operative complications after kidney transplantation.
To evaluate the incidence of rotator cuff ruptures, we examined 122 autopsy specimens of the shoulder and compared our results with those reported in the literature. The incidence of partial tears in our study was 28.7%; the incidence of complete rupture was 30.3%. The frequency increased with age. We found no cuff rupture without supraspinatus tendon involvement. Very often, the cuff tear was bilateral. We do not share the opinion that the rupture of the rotator cuff is primarily an injury of men. We found a higher incidence in female than in male shoulders.
In 50 patients of a geriatric hospital (33 women, aged 65-96 years, mean age 80 years, and 17 men, aged 68-91, mean age 78.3 years) calcium, albumin, phosphate, urea, creatinine, parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were determined. Forty patients with serum creatinine levels up to 1.4 mg/dl (124 mumols/l) and 10 patients with creatinine concentrations greater than or equal to 1.5 mg/dl (132 mumols/l) were evaluated. In patients with normal creatinine, a positive correlation was found between parathyroid hormone and age (r = 0.41; P less than 0.01). In patients with elevated creatinine, negative correlations were found in 1,25-dihydroxyvitamin D and calcium (r = -0.724; P less than 0.05), 1,25-dihydroxyvitamin D and creatinine (r = -0.79; P less than 0.01) and 1,25-dihydroxyvitamin D and phosphate (r = -0.87; P less than 0.002). The best correlation was observed in patients with elevated serum creatinine for 1,25-dihydroxyvitamin D and phosphate (r = -0.91; P less than 0.001). The results suggest that low levels of calcium and phosphate stimulate the 1-hydroxylation of 25-hydroxyvitamin D even in advanced age and that the calcium metabolism of these patients is frequently disturbed. Nineteen patients had low levels of 25-hydroxyvitamin D, indicating an insufficient supply of vitamin D or rare exposure to sunlight. In 49 of 50 patients, one ore more of the parameters of calcium metabolism were outside the normal range.
Saturated methylene blue solutions or powder were applied with a brush to fresh, unfixed brain slabs. The specimens were then exposed to ambient oxygen in a moist chamber. Fixation was done by application of an ammonium heptamolybdate solution followed by a phosphate-buffered paraformaldehyde/glutaraldehyde mixture with phosphomolybdic acid added. The specimens were dehydrated in tert-butanol before embedding in paraffin. Because of its high specificity for perikarya and for varicose, unmyelinated nerve fibres, this technique is a helpful supplement to other histological methods, particularly to myelin staining techniques. It is therefore well-suited for routine use in neuroanatomical research.
Eight healthy volunteers were studied under double-blind conditions after acute challenge with the peripheral beta 2-agonist reproterol, either alone or combined with the peripheral indirect cholinomimetic neostigmine. Their responses were also studied after administration of the centrally active indirect cholinomimetic physostigmine. The beta-adrenergic rise in heart rate was cholinergically suppressed. The beta-adrenergic rise of plasma cyclic adenosine monophosphate (cAMP) was not cholinergically modulated, while that of plasma glucose tended to be cholinergically suppressed. Physostigmine induced an anergic-anhedonic syndrome accompanied by physiological, metabolic, and neuroendocrine stress phenomena. The beta-adrenergic and cholinergic sensitivities, respectively, of the various parameters investigated tended to be nonsignificantly intercorrelated. Only a limited portion of the variance was explained by drug effects. Sensitivity to neostigmine was completely unrelated to sensitivity to physostigmine. Thus, cholinergic sensitivity seems not to be decisive for the fine tuning of the highly complex regulatory systems studied and peripheral sensitivity not to be representative for the central one, at least if unselective drugs like neostigmine and physostigmine are used.