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Biomedical subjects

W Braun

Publications and source records attributed to W Braun.

At least 217 records · Page 12Linked to original sources

Effects of DDT and dieldrin on intestinal glucose transport and brush border hydrolases. A comparison with phenobarbital and methylcholanthrene.

The enhancement of in vitro small intestinal transcellular glucose transport in NMRI mice after oral administration of the organic pesticides 2,4-DDT and dieldrin can be shown to be due to an increased active transport at the site of the brush border membrane. Intestinal disaccharidase activities were concomitantly elevated in the dieldrin group, while DDT produced no effects with intestinal hydrolases. The classic enzyme inducing agents phenobarbital and methylcholanthrene failed to stimulate intestinal glucose transport, although both increased intestinal disaccharidase activities considerably, thus questioning a close relation between these digestive and absorptive functions in the translocation of glucose. Intestinal alkaline phospatase activity was enhanced after DDT, dieldrin and methylcholanthrene treatment, but not with phenobarbital. It is suggested that DDT and dieldrin exert their stimulating effect on intestinal glucose transport by a mechanism different from general induction of metabolic pathways.

Animals↗

Representation of short and long-range handedness in protein structures by signed distance maps.

A new representation is proposed of short and long-range handedness in protein structures, by signed distance maps. This representation, based on the co-ordinates of the C alpha atoms of proteins, does not require the assignment of specific regular structures. The short-range handedness along the chain in alpha-helical, beta-strand and turn segments is shown, as well as the handedness between two strands of beta-sheet structures and for crossover connections. Results are given for a beta alpha beta alpha beta folding unit of flavodoxin, a beta alpha beta unit of subtilisin, which contains a left-handed crossover connection, and the domain 1 of bovine beta-trypsin.

Flavodoxin↗

Clinical experience with atenolol in patients with chronic liver disease.

The pharmacokinetics of atenolol were investigated following single intravenous (25 mg) and oral administration (100 mg) of atenolol in 13 patients with chronic liver disease and normal renal function and in 12 normal healthy volunteers. Four of the patients with chronic liver disease were not included in the statistical evaluation of kinetic data, since a reduction of creatinine clearance was observed during the course the study after ingestion of atenolol. A tendency to an increased distribution volume of atenolol could be observed in subjects with liver disease compared to normal volunteers. After intravenous and oral administration of atenolol, pharmacokinetic parameters such as elimination half-life, plasma clearance, and renal clearance did not differ significantly between patients with chronic liver disease and healthy volunteers. Thus, plasma half-life after intravenous dosing of atenolol was 6.0 +/- 0.46 hours in patients with hepatic disease and 5.0 +/- 0.4 hours in the controls, indicating absence of atenolol accumulation in hepatic failure. In the first days after starting beta-blocker therapy such as atenolol administration, parameters of kidney function as plasma creatinine, or possibly creatinine clearance, should be initially monitored at regular intervals, as there may be transient changes of renal function in patients with chronic liver disease, leading to delayed elimination of the drug.

Administration, Oral↗

[Age as an individual social syndrome (anthropologic and pedagogic remarks)].

The terms "social" and "gesellschaftlich" have in the German language almost an identical meaning although this was not originally the case. The modern conception of what is meant by "society" originated during the enlightenment. According to Rousseau this implied the subjection of the individual to the general will. This is the rule set by society. Originally "social" contained the meaning of the spontaneous relationship of a person to the world and his fellow-human beings. Older people, however, want to establish a direct social relationship again. Their needs are not met by the system of rules laid down by society. There is no pedagogical or therapeutic service-system based on the rules of society which can help them in this respect. What is required in the direct social relationship which transcends the "Ego" and leaves him a human-being. These considerations are particularly important regarding the proposals to reduce the years of employment.

Aged↗

High resolution nuclear magnetic resonance studies of the conformation and orientation of melittin bound to a lipid-water interface.

Previously, the size and stoichiometry of mixed micelles of perdeuterated dodecylphosphocholine and melittin were characterized and the 1H NMR spin systems of most amino acid residues of micelle-bound melittin identified. One- and two-dimensional 1H-1H Overhauser experiments have now been used to obtain qualitative information on intramolecular proton-proton distances. These data show that the N-terminal and the C-terminal segments of melittin form two spatially distinct, compact domains; using lipid spin labels these could be located near the micelle surface. For the C-terminal domain a detailed conformation was determined by using the distance contraints from the Overhauser studies as input for a distance geometry algorithm.

Animals↗

Determinants of allograft survival in 100 consecutive cadaver kidney transplants.

We reviewed 100 consecutive cadaver renal transplants done at our clinic between April 1976 and October 1979. A minimum 1-year followup was available on all patients. The actual 1-year graft survival rate was 64 per cent and the actual 1-year patient survival rate was 91 per cent. Criteria that had no significant effect on 1-year allograft survival were performance of pre-transplant nephrectomy and/or splenectomy, red blood cell group or the level of pre-formed antibody. A major determinant of graft survival was the number of blood transfusions received before transplantation. The 1-year graft survival rate was 36 per cent with no pre-transplant transfusions, 64 per cent with 1 to 5 transfusions and 70 per cent with more than 5 transfusions (p less than 0.005). The 1-year graft survival rate was not influenced by the use of kidneys imported from other states, the use of pediatric cadaver donors 1 to 15 years old or extended renal preservation times. Our experience supports continued regional and national sharing of adult and pediatric cadaver donor kidneys with extended preservation times.

Adolescent↗

A study of the probenecid effect on amino acid accumulation in kidney cortex slices.

The amount of amino acids accumulated by rat and mouse kidney cortex slices is determined by both membrane transport and intracellular metabolism, especially protein incorporation. Even with substrate concentrations of 100 microM up to 70% of the transported amino acids were found to be protein incorporated. Probenecid reduces the accumulation of the amino acids glycine, L-phenylalanine, L-valine, L-arginine, L-lysine, L-proline and alpha-AIB. At substrate concentrations of 100 microM the inhibition is between 28 and 66% (except alpha-AIB) with a probenecid concentration of 7.0 mM. Slight inhibitory effects were observed with 0.7 mM probenecid. The probenecid effect, however, is mainly on the protein incorporation. With 7.0 mM probenecid protein incorporation is reduced considerably, for some amino acids below 10% of the control values; small inhibitory effects were observed with concentrations of 0.7 mM. Amino acid transport is affected only slightly by probenecid. In consequence, higher accumulation rates of free amino acids may be measured after probenecid administration, preferentially with amino acids showing high initial incorporation rates.

Amino Acids↗

The influence of renal function on plasma levels and urinary excretion of acebutolol and its main N-acetyl metabolite.

The pharmacokinetics of acebutolol and its major N-acetyl metabolite diacetolol were determined following acute intravenous and chronic oral administration to 22 subjects with glomerular filtration rate (GFR) between 3 and 127 ml/min. Following chronic oral administration the mean terminal elimination half-life of unchanged acebutolol was about 10 hours independent of renal function, whereas the hall-life of the N-acetyl metabolite increased from 12.8 hr in subjects with normal renal function (GFR greater than 90 ml/min) to 24.0 hr in preuremic patients (GFR less than 10 ml/min). The mean area of the plasma level-time curve (AUC) of the metabolite was 14.2 mg 1-1 hr in patients with normal renal function and rose to a value of 81.4 mg 1-1 hr in preuremic patients. The mean AUC of the parent drug was not influenced by changes in renal function. The considerable accumulation of the acetyl metabolite, which has about the same beta blocking activity as the unchanged drug, necessitates dose reduction of acebutolol in the presence of different degrees of renal impairment (reduction by half of the normal daily dose in patients with GFR between 30 and 10 ml/min and by three quarters when GFR less than 10 ml/min). In subjects with normal renal function, the ratio between the AUC of the parent drug and that of its major N-acetyl metabolite was 3:1 after intravenous injection of the drug, while it was 1:2.5 following chronic oral administration, indicating a marked first pass metabolism of acebutolol.

Acebutolol↗

Combined use of proton-proton Overhauser enhancements and a distance geometry algorithm for determination of polypeptide conformations. Application to micelle-bound glucagon.

In a new approach for the determination of polypeptide conformation, experimental data on intramolecular distances between pairs of hydrogen atoms obtained from nuclear Overhauser enhancement studies are used as input for a distance geometry algorithm. The algorithm determines the limits of the conformation space occupied by the polypeptide chain. The experimental data are used in such a way that the real conformation should in all cases be within these limits. Two important features of the method are that the results do not depend critically on the accuracy of the distance measurements by nuclear Overhauser enhancement studies and that internal mobility of the polypeptide conformation is explicitly taken into consideration. The use of this new procedure is illustrated with a structural study of the region 19-27 of glucagon bound to perdeuterated dodecylphosphocholine micelles.

Amino Acid Sequence↗

Correlations between internal mobility and stability of globular proteins.

The recent work is surveyed which leads to the suggestions that the conformation of globular proteins in solution corresponds to a dynamic ensemble of rapidly interconverting spatial structures, that clusters of hydrophobic amino acid side chains have an important role in the architecture of protein molecules, and that mechanistic aspects of protein denaturation can be correlated with internal mobility seen in the native conformation. These conclusions resulted originally from high resolution 1H nuclear magnetic resonance (NMR) studies of aromatic ring mobility, exchange of interior amide protons and thermal denaturation of the basic pancreatic trypsin inhibitor and a group of related proteins. Various new approaches to further characterize proteins in solution have now been taken and preliminary data are presented. These include computer graphics to outline hydrophobic clusters in globular protein structures, high resolution 1H-NMR experiments at variable hydrostatic pressure and 13C-NMR relaxation measurements. At the present early stage of these new investigations it appears that the hydrophobic cluster model for globular proteins is compatible with the data obtained.

Amino Acids↗

Late ureteral obstruction and hematuria from de novo angiosarcoma in a renal transplant patient.

A patient is described with a long-term functioning renal allograft who presented with ureteral obstruction and hematuria from an angiosarcoma. The diagnosis of ureteral obstruction was established preoperatively with computerized tomography guided anterograde pyelography. This represents the first documented case of an angiosarcoma occurring de novo in a renal allograft recipient. Continued awareness is needed of the increased risk of malignancy following transplantation.

Adult↗

Elimination of guanfacine in patients with normal and impaired renal function.

1. Total body clearance and renal clearance after single intravenous doses of guanfacine were 360 +/- 262 (mean +/- s.d.) and 233 +/- 245 ml/min, respectively, in patients with normal renal function (glomerular filtration rate (GFR) > 90 ml/min), 308 +/- 274 and 34 +/- 22 ml/min, respectively, in patients with moderately impaired renal function (GFR 30-10 ml/min), and 257 +/- 187 and 18 +/- 15 ml/min, respectively, in preuremic patients (GFR < 10 ml/min). 2. The cumulative urinary excretion up to 48 h after a single intravenous injection of guanfacine was 57.0 +/- 32.0% in patients with GFR > 90 ml/min, 14.0 +/- 9.0% in patients with GFR 30-10 ml/min and 7.5 +/- 2.4% in preuremic patients. 3. In normal as well as impaired renal function the elimination rate constant of guanfacine was 0.05 h-1, which corresponds to an elimination half-life of 14 h, independent of renal function. 4. These results suggest that non-renal elimination of guanfacine plays an important role in patients with renal failure. 5. Intestinal absorption of guanfacine was calculated to be 59 +/- 19% in patients with GFR > 90 ml/min, to 68 +/- 16% in patients with GFR 30-10 ml/min, and to 73 +/- 36% in preuremic patients.

Absorption↗

Familial spontaneous pneumothorax and HLA antigens.

Twenty-three members of a family in which six persons had repeated spontaneous pneumothorces were studied for physical, chemical and genetic markers of this disease. A relationship between the HLA haplotype A2, B40, the alpha 1, antitrypsin phenotype M1 M2 and the occurrence of spontaneous pneumothorax was suggested in this family.

Adolescent↗