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Biomedical subjects

U Neumann

Publications and source records attributed to U Neumann.

At least 73 records · Page 4Linked to original sources
PubMed1997

Prophylactic use of low-dose urodilatin for prevention of renal impairment following liver transplantation: a randomized placebo-controlled study.

Many therapeutic measures have been employed to prevent or at least ameliorate postoperative renal impairment following liver transplantation. Recent clinical phase II studies have demonstrated that the new natriuretic peptide urodilatin has beneficial effects on renal function following heart and liver transplantation. The present study reports the first prospective randomized placebo-controlled trial of prophylactic urodilatin administration following liver transplantation. Seventy consecutive recipients of primary liver transplants were included in the study following randomization, and 33 patients continuously received urodilatin at a dose of 20 ng/kg/min for 7 d. The remaining 37 patients received a placebo infusion for the same time period. The course of serum creatinine and urea did not differ between the two groups nor did the daily urine production. However, the urodilatin group showed a higher preoperative median serum creatinine and a significant reduction on days 1 and 2, whereas this observation was not made in the placebo group. Furthermore, less furosemide was administered to the patients in the urodilatin group during the first 2 d. The incidence of postoperative hemodialysis and the number of treatments did not differ between the groups either (urodilatin group 4, vs. placebo group 6 and 22 for both groups, respectively). Side effects of the urodilatin therapy were not detected. The prophylactic low-dose urodilatin administration resulted in a trend towards amelioration of the renal function, but did not result in significant differences between the two experimental groups. Further studies, using higher doses, will be required to define the value of urodilatin for prevention of renal impairment after liver transplantation.

Adolescent↗
PubMed1996

A peptidoglycan binding domain in the porin-associated protein (PAP) of Rhodospirillum rubrum FR1.

The porin-associated protein of Rhodospirillum rubrum FR1 was found to contain a peptidoglycan binding motif. A partial fragment of 179 amino acids, obtained by cleavage of PAP with trypsin, Asp-N protease, and CNBr, was sequenced. Substantial sequence homology was found of the C-terminal part (residues 126-179) of porin-associated protein with OmpA, the peptidoglycan-associated lipoprotein of several bacteria, protein F of Pseudomonas aeruginosa, and PIII of Neisseria gonorrhoeae, the latter being also a porin-associated protein. The 179 amino acid fragment comprised about 67% of the mass spectrometrically determined total mass of PAP of 27850 Da.

Amino Acid Sequence↗
PubMed1996

Nitroglycerin versus epoprostenol: effects on hemodynamics, oxygen delivery, and hepatic venous oxygenation after liver transplantation.

Our objective was to determine the effects of vasodilatory treatment with epoprostenol (PGI2) and nitroglycerin (NTG) on systemic oxygen delivery index (DO2) and hepatic venous oxygen saturation (SvhO2) after liver transplantation. This prospective study used repeated-measures design. Fifteen adult patients undergoing orthotopic liver transplantation (OLT) were enrolled. Postoperatively, a fiberoptic pulmonary artery catheter was inserted into the right hepatic vein and a timed infusion of PGI2 and NTG was sequentially performed in random order at the following rates: PGI2 at 5 ng/kg/minute and NTG at 0.1 microgram/kg/minute. Each step in each sequence lasted 45 minutes, followed by a control interval of 45 minutes. Measurements were taken at the end of each period when hemodynamic function was stable. Systemic hemodynamics, DO2, oxygen uptake index (VO2), mixed venous oxygen saturation (SvO2), and SvhO2 were assessed. We found that PGI2 induced an increase of cardiac index (+18%, p < .05); DO2 (+16%, p < .05); and SvhO2 (+11%, p < .05). Mean arterial pressure was decreased during PGI2 infusion (-9%, p < .05), as well as during infusion of NTG (-10%, p < .05). NTG significantly decreased DO2 (-6%, p < .05) and SvhO2 (-4%, p < .05). Neither drug affected VO2. We conclude that PGI2 induced vasodilation and increased systemic oxygen delivery in parallel with SvhO2, suggesting a corresponding increase of hepatic oxygen supply. NTG induced systemic vasodilation and significantly impaired hepatic venous oxygen saturation and DO2. Thus, if vasodilatory therapy is indicated in the patient after liver transplantation, PGI2 appears to be better than NTG in improving DO2 without impairing splanchnic oxygenation.

Adult↗
PubMed1996

Incidence and outcome of arterial complications after orthotopic liver transplantation.

Arterial complications can be a major factor in morbidity and mortality after orthotopic liver transplantation (OLT), as they may cause graft failure, sepsis and complications of the biliary tract. From September 1988 to December 1994, 571 OLT were performed in 529 patients. The follow-up period ranged from 8 to 83 months. Actuarial 1-, 3- and 5-year survival figures were 91%, 87% and 85%, respectively. In 12 cases (2.1%) complications of the arterial anastomoses were observed. Early arterial complications occurred in eight cases from various causes, while late arterial complications were exclusively thromboses and developed in four patients 8, 12, 26 and 37 months after surgery, respectively. The main clinical course in patients with arterial thromboses was septic cholangitis with destruction of the biliary tree. Although 70% of the grafts with arterial thrombosis were lost, 30% could, at least temporarily, be salvaged by other treatment options. Provided adequate treatment is carried out, arterial complications do not affect overall patient survival.

Adolescent↗
PubMed1995

Glutamate-induced calcium responses in rat primary cortical cultures are potentiated by co-administration of glutamate transport inhibitors.

The effects of glutamate uptake inhibitors on the L-glutamate-induced increase in intracellular calcium concentrations were assessed in rat primary cortical cultures. The glutamate (10 microM)-induced rise in intracellular calcium concentrations was strongly and dose dependently increased and prolonged by simultaneous administration of micromolar concentrations of the reference glutamate transport inhibitors, L-trans-pyrrolidine-2,4-dicarboxylate (PDC) and D- or L-threo-beta-hydroxyaspartate. PDC in concentrations up to 10 microM showed no effect on intracellular calcium when administered alone. The anticancer drug tamoxifen, which was found to be effective as a glutamate transport inhibitor, did not increase but prolonged the cellular calcium response to glutamate, indicating that it had a different mechanism of action compared to that of standard glutamate transport inhibitors. The findings suggest that compounds which inhibit the glutamate transporter may potentiate the excitatory glutamatergic signal of cultured neurons when administered together with glutamate.

Animals↗
PubMed1995

Internally quenched fluorogenic substrate for furin.

A new substrate for furin, Abz-Arg-Val-Lys-Arg-Gly-Leu-Ala-Tyr(NO2)-Asp-OH, has been synthesized and characterized. The peptide is an internally quenched fluorogenic substrate. The kinetic parameters are Km = 3.8 microM, kcat = 29.3 s-1, and kcat/KM = 7,710,000 M-1 s-1. The substrate is efficiently cleaved by furin; its kcat/KM value is over 2000-fold higher than that of the commonly used substrate Boc-Arg-Val-Arg-Arg-AMC.

Amino Acid Sequence↗
PubMed1995

[Immunologic tolerance after experimental liver transplantation].

Allografts in the rat liver are rejected less vigorously than other primarily vascularized allografts; they show a better survival rate and induce donor-specific unresponsiveness or tolerance in some donor-recipient combinations. This overview focuses on the immunologic mechanisms of this privileged status of liver allografts. A variety of possible mechanisms, such as generation of suppressor T-cells, humoral factors and microchimerism, has been related to the observed hyporeactivity. A further analysis of these phenomena may enhance the development of clinical organ transplantation protocols that allow for establishment of donor-specific unresponsiveness without the need for life-long immunosuppression.

Animals↗
PubMed1995

Localization of alpha-fetoprotein in developing chick amniotic membrane.

The aim of this work was to investigate the localization of alpha-fetoprotein (AFP) in amniotic membrane (AM). By using the immunoperoxidase technique in several developmental stages, which reflected the changes of structure of the AM germinal layers, AFP was detected earliest in 7-day AM and localized selectively in the ectodermal cell layer. This was the only developmental stage at which AM occurred as a two-layer structure, ectoderm and somatic mesoderm, and was AFP-positive. In the zone of fusion of the AM with the inner wall of the allantoic sac, cystlike cavities were observed which were markedly immunoreactive to AFP. In those membranes where fusion had consolidated and a four-layer structure could be distinguished: ectoderm, somatic mesoderm, splanchnic mesoderm and endoderm, AFP was localized in the ectodermal cells and in the splanchnic mesoderm resulting from the inner wall of the allantoic sac. Both mesodermal layers could be distinguished by means of the AFP immunoreaction since AFP labelled the splanchnic, but not the somatic mesoderm. At later developmental stages, e.g. 18-day, the AM had a three-layer structure and AFP was localized selectively throughout the splanchnic mesoderm. The disappearance of the somatic mesoderm coinciding temporarily with the disappearance of AFP from the ectodermal cells, suggests that the presence of AFP in such cells could depend on some factors related to the somatic mesoderm.

Amnion↗
PubMed1995

[Cerebral ischemia during implantation of automatic defibrillators].

In order to study the influence of repetitive episodes of ventricular fibrillation (VF) during defibrillator implantation on the electrical activity of the brain, we performed an electroencephalographic (EEG) monitoring during implantation procedure in 18 patients. For defibrillation threshold testing 62 episodes of VF (1-6 episodes per patient) were induced. The mean duration of VF was 20 +/- 12 s; the mean duration of hypotension during an episode (defined as a mean arterial pressure of 50 mm Hg or less) was 33 +/- 16 s. EEG monitoring was performed using the International 10-20 System. The duration of cardiac arrest-related EEG alteration was assessed by an experienced neurologist and could be determined in 41 test-episodes; in 21 episodes analysis was not possible due to poor recordings. Ischemia-related EEG changes started 7.8 +/- 4.6 s after VF induction and lasted 64 +/- 49 s (range, 12-240). The duration of EEG alteration was significantly (p < .001) correlated with the duration of VF episodes (r = .71) and the associated hypotension (r = .82). With regard to patients the duration of ischemia related EEG changes also correlated significantly (p = .001) with the individual cumulative duration of VF (r = .85) and the associated hypotension (r = .88). In females EEG changes lasted longer than in males (p = .03); this finding, however, was only based on 2 women. Other clinical parameters, such as patient age, degree of congestive heart failure, left ventricular ejection fraction, stroke volume and cardiac index, the order of episodes within the testing sequence, and the time interval between episodes did not correlate with the duration of EEG alteration after VF induction. The duration of ischemia-related EEG alteration during VF episodes depends on the duration of cardiac arrest. In females EEG changes tended to last longer than in males, however, this finding has to be confirmed. An association with other clinical parameters has not been observed. Limitation of VF duration appears to be the most important factor to avoid prolonged cerebral ischemia.

Adult↗
PubMed1995

[Graft-vs.-host reaction: a severe complication after orthotopic liver transplantation].

INTRODUCTION: Patients with solid-organ transplantation are at risk for Graft-versus-host disease (GVHD) even though GVHD is a rare phenomenon after orthotopic liver transplantation (OLT). CASE REPORT: The 30 yrs old male patient received an ABO compatible orthotopic liver graft for acute liver failure due to intoxication with amanita phalloides. Twenty-four days after OLT the patient developed high temperatures up to 40.0 degrees C and pancytopenia and was treated for CMV-infection. On postoperative day (POD) 32 an erythematous maculo-papular rash developed. A drug induced toxic epidermal necrolysis was suspected and treated with plasmapheresis for three days. Acute renal failure and respiratory insufficiency occurred while liver function was not impaired. A skin biopsy at that time showed no specific signs for GVHD. On POD 42 HLA-typing of circulating lymphocytes presented donor HLA phenotype and GVHD was established. Therapy with ATG was started but the clinical status of the patient did not improve. Following administration of OKT3 on POD 48 a reduction of activated CD-3 lymphocytes from 90% to 60% could be achieved. Due to the low platelet count the patient died of intracerebral hemorrhage on POD 52. CONCLUSION: Since a fully developed GVHD is rare after OLT and the similarity of the clinical findings to viral or drug induced diseases is high, diagnosis is often made late in the course of the disease. Furthermore, therapeutic measures for GVHD are scarce and diagnosis has to be established as early as possible, hence pretransplant procurement of donor and recipient mononuclear cells for later study should be considered to decrease the time period between clinical suspicion and diagnosis.

Adult↗
PubMed1995

[Electrophoretic analysis on the proteolytic decomposition of of FSH preparations].

We investigated the influence of some proteolytic enzymes being present in the digestive canal (pepsin, trypsin, chymotrypsin) on the digestion of porcine FSH-samples by electrophoresis. Trypsin and Chymotrypsin digested the 18-kDa-protein much faster than pepsin, whereas a 67-kDa-protein was much faster digested by Pepsin than by Trypsin or Chymotrypsin. The overall proteolytic effect of Chymotrypsin is small compared with Pepsin and Trypsin. A subsequent digestion with Pepsin, Trypsin and Chymotrypsin led to a complete proteolysis of all proteins being present in the sample.

Animals↗
PubMed1994

N-(sulfonyloxy)phthalimides and analogues are potent inactivators of serine proteases.

A series of 2-(sulfonyloxy) and 2-(acyloxy)-1H-isoindole-1,3(2H)-diones and analogous 1H-benz[de]isoquinoline-1,3(2H)-diones was prepared, and their potential to inactivate chymotrypsin was investigated. The N-(sulfonyloxy) and N-(acyloxy)phthalimides were found to be potent inactivators of chymotrypsin and related serine proteinases. For the most active compounds, N-(dansyloxy)phthalimide and N-(tosyloxy)phthalimide, the second-order rate constant of chymotrypsin inactivation was in the range of 250,000 m-1 s-1. N-(Mesyloxy)-phthalimide was the most active compound for inactivation of leukocyte elastase. It was shown that these compounds act as true suicide substrates. Enzyme-catalyzed opening of the heterocyclic ring results in the formation of an acyl-enzyme with attached O-acyl or O-sulfonylhydroxamic acid moiety. Subsequent Lossen rearrangement leads to the formation of a highly reactive isocyanate, which irreversibly modifies the target protease.

Acylation↗
PubMed1994

A novel fluorogenic substrate for ribonucleases. Synthesis and enzymatic characterization.

The synthesis and enzymatic characterization of DUPAAA, a novel fluorogenic substrate for RNases of the pancreatic type is described. It consists of the dinucleotide uridylyl-3',5'-deoxyadenosine to which a fluorophore, o-aminobenzoic acid, and a quencher, 2,4-dinitroaniline, have been attached by means of phosphodiester linkages. Due to intramolecular quenching the intact substrate displayed very little fluorescence. Cleavage of the phosphodiester bond at the 3'-side of the uridylyl residue by RNase caused a 60-fold increase in fluorescence. This allowed the continuous and highly sensitive monitoring of enzyme activity. The substrate was turned over efficiently by RNases of the pancreatic type, but no cleavage was observed with the microbial RNase T1. Compared to the dinucleotide substrate UpA, the specificity constant with RNase A, RNase PL3 and RNase U(s) increased 6-, 18-, and 29-fold, respectively. These differences in increased catalytic efficiency most likely reflect differences in the importance of subsites on the enzyme in the binding of elongated substrates. Studies on the interactions of RNase inhibitor with RNase A using DUPAAA as a reporter substrate showed that it was well suited for monitoring this very tight protein-protein interaction using pre-steady-state kinetic methods.

Aminobenzoates↗
PubMed1994

Quantitation of electrophoretically separated proteins in the submicrogram range by dye elution.

A new method for the fast, reliable and reproducible submicrogram quantitation of proteins separated by different electrophoretic techniques is presented. The method is based on a modified sensitive staining technique using Coomassie Brilliant Blue G-250 in colloidal solution combined with an optimized elution procedure of the bound dye in a 3% w/v solution of sodium dodecyl sulfate followed by photometric determination of dye concentration in the eluate. In addition a new method is provided for background correction, even suitable for gels showing strong background staining. The staining procedure allows the detection of 20 ng depending on the nature of the protein and the separation technique used. Quantitation is linear at least in the range from 50 ng to 10 micrograms and highly reproducible even under non-optimized conditions. The presented method can be applied to sodium dodecyl sulfate-electrophoresis, isoelectric focusing and two-dimensional electrophoresis.

Electrophoresis, Polyacrylamide Gel↗
PubMed1994

Interaction of semisynthetic variants of RNase A with ribonuclease inhibitor.

Derivatives of ribonuclease A (RNase A) with modifications in positions 1 and/or 7 were prepared by subtilisin-catalyzed semisynthesis starting from synthetic RNase 1-20 peptides and S-protein (RNase 21-124). The lysyl residue at position 1 was replaced by alanine, whereas Lys-7 was replaced by cysteine that was specifically modified prior to semisynthesis. The enzymes obtained were characterized by protein chemical methods and were active toward uridylyl-3',5'-adenosine and yeast RNA. When Lys-7 was replaced by S-methyl-cysteine or S-carboxamido-contrast, the catalytic properties were only slightly altered. The dissociation constant for the RNase A-RI complex increased from 74 fM (RNase A) to 4.5 pM (Lys-1, Cys-7-methyl RNase), corresponding to a decrease in binding energy of 10 kJ mol-1. Modifications that introduced a positive charge in position 7 (S-aminoethyl- or S-ethylpyridyl-cysteine) led to much smaller losses. The replacement of Lys-1 resulted in a 4-kJ mol-1 loss in binding energy. S-protein bound to RI with Ki = 63.4 pM, 800-fold weaker than RNase A. This corresponded to a 16-kJ mol-1 difference in binding energy. The results show that the N-terminal portion of RNase A contributes significantly to binding of ribonuclease inhibitor and that ionic interactions of Lys-7 and to a smaller extent of Lys-1 provide most of the binding energy.

Animals↗