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Biomedical subjects

W Kramer

Publications and source records attributed to W Kramer.

At least 37 records · Page 2Linked to original sources
PubMed1990

Cardiac structure and function in continuous ambulatory peritoneal dialysis: influence of blood purification and hypercirculation.

Continuous ambulatory peritoneal dialysis (CAPD) is associated with obvious hemodynamic and blood purification advantages over intermittent hemodialysis. To determine whether this is reflected in favorable left ventricular (LV) structure and function, a group of 55 normotensive patients (aged 58.4 +/- 11.0 years) undergoing CAPD was analyzed by means of echocardiography. Characteristic findings were LV hypertrophy (158 +/- 50 gm/m2), mainly the result of septal thickening (13.3 +/- 2.8 mm), and left atrial dilatation (40.9 +/- 7.4 mm). Mean LV diameter in end diastole and end systole and posterior wall thickness were normal. Parameters of LV systolic function (ejection fraction [EF]: 62.0 +/- 13.0%; velocity of circumferential fiber shortening [Vcf]: 1.58 +/- 0.46 circ/sec) were in the upper normal range at a hyperdynamic circulatory state (cardiac index [CI] 4.67 +/- 1.82 L/min/m2. The amount of LV hypertrophy was related to the amount of hypercirculation (CI: p less than 0.001; hemoglobin: p less than 0.025) and quality of blood purification (creatinine, urea: p less than 0.02) but not to blood pressure, age, or duration of dialysis. Left atrial dilatation was inversely related to LV systolic function (EF, Vcf: p less than 0.001) and directly related to LV muscle mass (p less than 0.02). A low prevalence (13%) of pericardial effusion was independent of blood purification. We conclude that in normotensive patients receiving CAPD, a high prevalence of left atrial dilatation and asymmetric septal hypertrophy is found, the latter being related both to the amount of hypercirculation and the quality of blood purification.

Adult↗
PubMed1990

Mismatch repair-induced meiotic recombination requires the pms1 gene product.

The presence of multiple heterologies in a 9-kilobase (kb) interval results in a decrease in meiotic crossovers from 26.0% to 10.1%. There is also an increase from 3.5% to 11.1% in gene conversions and ectopic recombinations between the flanking homologous MAT loci. The hypothesis that mismatch repair of heteroduplex DNA containing several heterologies would lead to a second round of recombination has now been tested by examining the effect of a mutation that reduces mismatch correction. The repair-defective pms1-1 allele restores the pattern of recombination to nearly that seen in congenic diploids without the heterologies. Mismatch repair-induced recombination causes a significant increase in MAT conversions and ectopic recombination events with as few as two heterozygosities separated by 0.3-0.7 kb, but not when the mismatches are separated by greater than 1 kb. The frequency of these events depends on both the number and position of the heterozygosities relative to the flanking homologous MAT loci used to detect the events. The creation of recombinogenic lesions by mismatch repair in yeast could be analogous to the creation of recombinogenic lesions in dam- Escherichia coli. We suggest that the repair of heteroduplex DNA containing multiple mismatches may produce chromosomal rearrangements and gamete inviability when naturally polymorphic chromosomes undergo meiotic recombination.

Alleles↗
PubMed1990

[Chronic heart failure: effect and evaluation of therapy with positive inotropic substances].

In congestive heart failure (CHF), even today, pharmacotherapy renders primarily only symptomatic improvement. The success of the treatment is basically dependent on the degree of functional myocardial impairment, that is, the condition of the inadequately treatable underlying disease. Treatment should be differentially oriented to the nature of the LV dysfunction as systolic or diastolic whereby the latter may account for 20 to 40% of those with CHF. In the case of diastolic LV dysfunction, because of the impaired compliance, vasodilators are not beneficial since small changes in volume may cause marked changes in filling pressures and vice versa. Additionally, inotropic substances are unfavorable since they further increase filling pressure and impedance, that is, diastolic LV function may become more compromised. For systolic LV dysfunction both vasodilators and positive inotropic substances can be employed. Some unsettled issues remaining include the appropriate time to begin treatment, the most suitable form of combined treatment and the best dosing regimens. Digitalis, as dobutamine, increases measured contractility; those seen to profit from digitalis include symptomatic patients with LV dilatation and impaired pump function as well as patients with supraventricular tachyarrhythmias. Prior to use of positive inotropic drugs in CHF, consideration should be given to whether favorable acute effects can be maintained during longterm treatment, adverse reactions such as arrhythmogenicity are acceptable, and the actions on myocardial oxygen balance. New nonglycoside positive inotropic agents which can also be administered orally, acutely improve hemodynamics; these include catecholamine derivatives, phosphodiesterase inhibitors (PDH). Both substance groups increase contractility but arrhythmogenicity as well, in general via increased concentrations of intracellular cyclic AMP. Reservations regarding the use of positive inotropic drugs for CHF have been supported by the results of studies showing that beta 1 agonists such as prenalterol and beta 2 agonists such as salbutamol or pirbuterol, due to down-regulation of beta-receptor density, are not capable of maintaining improved contractility during chronic treatment; intermittent dobutamine treatment resulted in higher mortality; beta-blockers without intrinsic sympathomimetic activity reduced mortality in patients with CHF after myocardial infarction while on use of beta-receptor blockers with intrinsic sympathomimetic activity, this favorable effect was not observed; during chronic PDH treatment, there was an unfavorable one-year mortality rate (50 to 100%); a controlled study with amrinone did not show a higher mortality than placebo. For most PDH, it is not known with certainty at which therapeutically effective dose the positive inotropic effect can best be realized and whether the acute hemodynamic effects are not predominantly attributable to the vasodilatory properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiomyopathy, Dilated↗
PubMed1990

[Pulmonary function parameters of shock lung patients--results of a follow-up study].

In seventeen patients out of a total of 219 survivors who had received long-term ventilation for pulmonary failure, an examination was carried out to clarify the question as to late pulmonary sequelae. The following sequelae were detected: 1. a diffusion disturbance in five cases, 2. load-dependent pulmonary hypertension in four cases, and 3. a considerable reduction in compliance.

Adult↗
PubMed1990

Tumour imaging of bladder carcinomas and their metastases with 111indium-labelled monoclonal anti-CEA antibody BW 431/26.

Fifty-one patients with muscle-infiltrating bladder carcinoma (T2-T4, N0-3, M0-1) were studied with a new imaging technique using murine monoclonal antibody directed against the carcinoembryonic antigen (CEA). A total number of 67 investigations were performed. The intact 111indium-labelled antibody (BW 431/26, Behringwerke Marburg) detected 86% of primary tumours, 93% of local and 75% of distant metastases whether there was an elevated CEA level in serum or not. Immunohistologically (avidin-biotin-peroxidase method) positive frozen tissue sections from tumour biopsies stained with the same monoclonal anti-CEA antibody, thus confirming the presence of the CEA antigen in vitro. The method was of much higher sensitivity in detecting even very small metastases than X-ray computed tomography (86% versus less than 30%). The specificity was in the region of 90%. The response to chemotherapy (MVEC regimen) was shown by repeated studies demonstrating reduced uptake (partial remission) or no accumulation (complete remission) in the second immunoscan. We suggest immunoscintigraphy of bladder tumours and their metastases as an additional method in preoperative staging and postoperative care.

Antibodies, Monoclonal↗
PubMed1989

Efficient oligonucleotide-directed construction of mutations in expression vectors by the gapped duplex DNA method using alternating selectable markers.

An efficient method for the construction of multiple mutations in a sequential manner is described. It is based on the gapped duplex DNA approach to oligonucleotide-directed mutagenesis (Kramer et al. 1984, Nucl. Acids Res. 12, 9441-9456) and a set of newly constructed phasmid vectors. These are characterized by the following features. Presence of the phage fl replication origin permits ready conversion to the single stranded DNA form. An amber mutation within, alternatively, the bla or cat gene provides a means for ready selection of the strand into which the mutagenic oligonucleotide has been incorporated. By means of the alternating antibiotic resistance markers any number of mutations can be constructed in consecutive rounds of mutagenesis. The optional presence of gene expression signals allows the direct overproduction of structurally altered proteins without re-cloning. Both the mutagenesis and expression aspects were tested using the lacZ gene as a model.

Escherichia coli↗
PubMed1989

Influence of the new class I antiarrhythmic agent diprafenone on the end-systolic pressure-volume relationship (conductance technique).

To evaluate cordiodepressive risks of antiarrhythmic treatment with diprafenone, we monitored, in addition to conventional hemodynamic parameters, end-systolic pressure-volume relations to assess potential negative inotropic effects. Thirteen patients underwent hemodynamic analysis with and without the influence of diprafenone 1.5 mg/kg, both a) at rest (paced heart rate of 90 beats/min and b) during tachycardia (paced tachycardia of 160 beats/min). Left ventricular volumes increased under the influence of diprafenone, both at rest (end-diastolic volume by an average of 12%, end-systolic volume by 21%) and during tachycardia (by 15% and by 47%, respectively). Diprafenone induced a depression of left ventricular function during tachycardia only: Ejection fraction fell by an average of 25% and stroke work by 19%, while end-diastolic pressure increased by an average of 28% and systemic vascular resistance by 34%. Diprafenone caused the loops of the end-systolic pressure-volume relationship to move rightward and decreased the slope k, indicating negative entropy, both at rest and during tachycardia. Thus, since under the influence of diprafenone negative inotropic effects and depressed left ventricular function were found (while determinants of preload and afterload increased), diprafenone should not be used as an antiarrhythmic agent in patients with advanced cardiac failure.

Anti-Arrhythmia Agents↗
PubMed1989

Cloning and nucleotide sequence of DNA mismatch repair gene PMS1 from Saccharomyces cerevisiae: homology of PMS1 to procaryotic MutL and HexB.

The PMS1 gene from Saccharomyces cerevisiae, implicated in DNA mismatch repair in yeast cells (M. S. Williamson, J. C. Game, and S. Fogel, Genetics 110:609-646, 1985), was cloned, and the nucleotide sequence was determined. The nucleotide sequence showed a 2,712-base-pair open reading frame; the predicted molecular mass of the deduced protein is 103 kilodaltons. Deletion mutants of the open reading frame were constructed and genetically characterized. The deduced amino acid sequence of the PMS1 gene exhibited homology to those of the mutL gene from Salmonella typhimurium and the hexB gene from Streptococcus pneumoniae, genes required for DNA mismatch repair in these organisms. The homology suggests an evolutionary relationship of DNA mismatch repair in procaryotes and eucaryotes.

Amino Acid Sequence↗
PubMed1989

Heteroduplex DNA correction in Saccharomyces cerevisiae is mismatch specific and requires functional PMS genes.

In vitro-constructed heteroduplex DNAs with defined mismatches were corrected in Saccharomyces cerevisiae cells with efficiencies that were dependent on the mismatch. Single-nucleotide loops were repaired very efficiently; the base/base mismatches G/T, A/C, G/G, A/G, G/A, A/A, T/T, T/C, and C/T were repaired with a high to intermediate efficiency. The mismatch C/C and a 38-nucleotide loop were corrected with low efficiency. This substrate specificity pattern resembles that found in Escherichia coli and Streptococcus pneumoniae, suggesting an evolutionary relationship of DNA mismatch repair in pro- and eucaryotes. Repair of the listed mismatches was severely impaired in the putative S. cerevisiae DNA mismatch repair mutants pms1 and pms2. Low-efficiency repair also characterized pms3 strains, except that correction of single-nucleotide loops occurred with an efficiency close to that of PMS wild-type strains. A close correlation was found between the repair efficiencies determined in this study and the observed postmeiotic segregation frequencies of alleles with known DNA sequence. This suggests an involvement of DNA mismatch repair in recombination and gene conversion in S. cerevisiae.

Alleles↗
PubMed1989

Present use of positive inotropic drugs in heart failure.

Cardiac failure is treated with increasing success by phosphodiesterase-III (PDE-III) inhibitors such as amrinone, milrinone, and enoximone. While relatively pure positive inotropic substances (e.g., dopamine and dobutamine) are limited by tolerance development and MVO2 increase, the efficacy of PDE inhibitors is maintained by avoiding catecholamine and beta-receptors. They have positive inotropic, positive lusitropic, and vasodilatatory properties; myocardial oxygen consumption remains unaltered. PDE-III inhibitors act by selectively inhibiting PDE-III, leading to an increased cAMP concentration in myocardial and smooth muscle cells. In contrast, forskolin increases intracellular cAMP by activation of adenylate cyclase. It could be shown that parenteral administration of the PDE inhibitors sulmazole, amrinone, and enoximone resulted in preload and afterload reduction due to vasodilation with concomitant decrease of peripheral and pulmonary vascular resistance; they also led to elevated cardiac output and ejection fraction as well as a significant increase in dp/dtmax, while left ventricular filling pressures were markedly lowered. Pulmonary pressure values fell significantly, whereas heart rate and myocardial oxygen consumption showed no clinically relevant alterations. In patients with angiographically documented coronary artery disease, the anti-ischemic efficacy of enoximone could be proven both during exercise and stress pacing. The decrease of the pathologically elevated pulmonary pressures during ischemia was accompanied by reduced ST-segment depression following enoximone without changing MVO2 significantly. First tests after intracoronary application of enoximone confirmed its direct myocardial efficacy, indicating its positive inotropic and lusitropic properties. Thus, patients in cardiac failure have useful therapeutic alternatives at their disposal when taking PDE inhibitors. The anti-ischemic properties of these drugs need further evaluation.

Cardiotonic Agents↗
PubMed1989

Asymmetric septal hypertrophy and left atrial dilatation in patients with end-stage renal disease on long-term hemodialysis.

Some literature reports associate a reduced weekly duration of treatment (3 x 4 h/week) for patients on maintenance hemodialysis with an increased cardiovascular mortality. To determine whether the improved survival of patients on long weekly hemodialysis (LHD: 3 x 8 h/week) can be associated with different cardiac changes, the cardiac characteristics of a group of 50 patients on LHD were analyzed in a non-invasive assessment. The main findings were an increased left ventricular (LV) muscle mass (176 + 54 g/m2), mass/volume ratio (1.69 + 0.37 g/ml) and left atrial diameter (39.7 + 5.7 mm). The increase in LV muscle mass was due mainly to a high prevalence of asymmetric septal thickening. The ratio septum/LV posterior wall was directly correlated with the left atrial diameter (r = 0.52), LV end-diastolic diameters were inversely correlated with hemoglobin concentration (r = 0.62). LV dilatation and/or LV systolic dysfunction were not characteristic findings: Only 6% of patients had a moderately enlarged (less than 65 mm) LV diameter, LV ejection fraction was decreased in 12%. There was no significant correlation between the degree of LV hypertrophy or left atrial dilatation and patient age, total dialysis duration, interdialytic weight gain, hemoglobin concentration, parameters of blood purification, blood pressure before and after dialysis, history of hypertension. We conclude that cardiac characteristics in patients on LHD are comparable to those described for large patient groups on short hemodialysis. Our findings do not explain improved survival on LHD.

Adult↗
PubMed1989

[Observations on post-traumatic osteitis].

The following study reports the frequency, the promoting factors, the therapy and her results of the 32 patients with posttraumatic osteitis we treated between 1984 and 1986 in the Surgical University Clinic Tübingen. Most of the primary injuries were caused by traffic-accidents; especially dangerous were those with motor-bikes, which led frequently via open fractures of the shank to osteitis. We saw the highest infection-rates after plate-osteosyntheses. The infects became obvious in most cases either about one month after the accident or a year later coinciding with the increased use of the limb. The most frequent bacterium was Staph. aureus both in the mono-infections and in the mixed-infections forming a third of the group. We always performed an operative therapy with the intention to stabilize the bone and to clean the infection-site. The strict performance of this management led to infect-suppression in all cases with the need of only one amputation.

Adult↗
PubMed1989

3-Diazirine-derivatives of bile salts for photoaffinity labeling.

New carbene-generating photolabile bile salt derivatives, 3,3-azo-7 alpha,12 alpha-dihydroxy-5 beta [7 beta-3H]cholan-24-oic acid and (3,3-azo-7 alpha,12 alpha-dihydroxy-5 beta [7 beta-3H]cholan-24-oyl)-2- aminoethanesulfonic acid were synthesized with high specific radioactivity. These 3-diazirine-derivatives could be activated to the corresponding carbenes by irradiation with ultraviolet light at 350 nm with a half-life time of 2 min. The 3-diazirine derivatives behaved in enterohepatic circulation like the natural bile salts. The uptake of [3H]taurocholate into isolated hepatocytes was competitively inhibited by (3,3-azo-7 alpha,12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2- aminoethanesulfonic acid indicating that the 3,3-azo-derivative of taurocholate shares the hepatic transport systems for natural bile salts. It was demonstrated that the radioactively labeled 3-diazirine bile salt derivatives are useful probes for photoaffinity labeling of bile salt binding proteins especially in intact cells and tissues.

Affinity Labels↗
PubMed1988

Specific alterations of rat renal microsomal proteins induced by cephaloridine.

In order to elucidate the molecular mechanisms of cephaloridine (CPH) nephrotoxicity, the effect of cephaloridine treatment on the protein composition of different subcellular fractions from rat kidney cortex was investigated. After intravenous treatment of male Wistar rats with 250-1200 mg/kg/d CPH for 1-3 days, kidneys were removed and the homogenate from renal cortex was separated into lysosomal, cytosolic and microsomal fractions. The polypeptide composition of the different subfractions was analyzed by one-dimensional SDS-gel electrophoresis and quantified by densitometry. Significant differences in the polypeptide composition between treated and non-treated animals were seen in the microsomal fraction. CPH-treatment induced a polypeptide with an apparent molecular weight of 44,000 and decreased the content of cytochrome P-450 isoenzymes in the microsomal fraction. Solubilization experiments showed that the CPH-induced microsomal polypeptide of molecular weight 44,000 is a peripheral membrane protein rather than an integral membrane protein. The induction of this protein by CPH was dose- and time-dependent. Preliminary experiments using the kidney slice technique indicate that the induction of this polypeptide correlates with the nephrotoxicity measured as decrease in renal cortical accumulation of organic ions. Thus, the results of the present study indicate that treatment of rats with CPH resulted in the induction of a microsomal polypeptide of molecular weight 44,000 which could be a sensitive parameter of cephaloridine nephrotoxicity.

Animals↗
PubMed1988

Inactivation of the intestinal uptake system for beta-lactam antibiotics by diethylpyrocarbonate.

The uptake system for beta-lactam antibiotics in the rabbit small intestine was investigated using brush-border membrane vesicles. After treatment of membrane vesicles with the reagent diethylpyrocarbonate (DEP), the uptake of orally active beta-lactam antibiotics with an alpha-amino group in the substituent at position 6 or 7 of the penam or cephem nucleus was significantly inhibited, whereas DEP-treatment had no inhibitory effect on the uptake of beta-lactam antibiotics without an alpha-amino group. The kinetic analysis revealed an apparent competitive inhibition indicating a decreased affinity of the transport system for alpha-amino-beta-lactam antibiotics. Substrates of the intestinal dipeptide transport system - dipeptides and alpha-amino-beta-lactam antibiotics - could protect the transport system from irreversible inhibition by DEP, whereas beta-lactam antibiotics without an alpha-amino group as well as amino acids or bile acids had no effect. Incubation of DEP-treated vesicles with hydroxylamine led to a partial restoration of the transport activity indicating that DEP may have led to a modification of a histidine residue of the transport protein. From the data presented we conclude that a specific interaction of the alpha-amino group in the substituent at position 6 or 7 of the penam or cephem nucleus presumably with a histidine residue of the transport protein is involved in the translocation process of orally active alpha-amino-beta-lactam antibiotics across the intestinal brush-border membrane.

Animals↗
PubMed1988

Oligonucleotide-directed construction of mutations: a gapped duplex DNA procedure without enzymatic reactions in vitro.

The gapped duplex DNA approach to oligonucleotide-directed construction of mutations (Kramer et al. 1984, Nucl. Acids Res. 12, 9441-9456) has been developed further. A procedure is described that makes in vitro DNA polymerase/DNA ligase reactions dispensable. Direct transfection of host bacteria with gdDNA molecules of recombinant phage M13 plus mutagenic oligonucleotide results in marker yields in excess of 50% (gap size 1640 nucleotides). An important feature incorporated into the mutagenic oligonucleotide is the presence of one or two internucleotidic phosphorothioate linkages immediately adjacent to the 5'-terminus. Automated preparation and biochemical properties of such compounds are described as well as their performance in oligonucleotide-directed mutagenesis. A systematic study of the following parameters influencing marker yield is reported: Gap size, length of oligonucleotide, chemical nature of oligonucleotide termini and heatshock temperature during transformation.

Base Sequence↗