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Biomedical subjects

W Kramer

Publications and source records attributed to W Kramer.

232 records · Page 13Linked to original sources
PubMedDate not supplied

Rational design of an improved induction scheme for recombinant Escherichia coli.

In Escherichia coli, strong overexpression of a recombinant protein has been shown to be deleterious due to a heavy metabolic burden on the host cell, which may completely cease cell growth before maximum product accumulation has occurred. Aiming at a reduction of very high product formation rates, we engineered E. coli strains by mutating the Leloir pathway for galactose metabolization, so that galactose can be utilized to induce lac derived promoters. The induction with galactose was effective in every strain and expression construct tested, and it reduced the metabolic burden on a highly overproducing clone so that cell growth and product accumulation could be maintained for several generations.

Escherichia coli↗
PubMedDate not supplied

AR-L 115 in coronary artery disease: positive inotropic effects and increase of left-ventricular pump function without inducing angina.

1. AR-L 115 improves pump function in patients with advanced and fully treated congestive cardiomyopathy. Since, in spite of such beneficial responses, the energy cost involved might be detrimental when used in advanced coronary artery disease, we monitored clinical haemodynamic and ECG responses to AR-L 115 (2 mg/kg body weight, bolus) in ten patients with coronary artery disease who had developed angina pectoris and/or pathological increases in left ventricular-end diastolic pressure (LVEDP) at the end of a 1 min pacing stress test. 2. When subjected to these stress conditions again (but this time during the peak effect of AR-L 115), there was no longer evidence of ischaemic myocardial impairment, neither clinically by ECG or haemodynamically. 3. There were (average) increase of 43% in cardiac index, 16% in heart rate, 27% in stroke index, 20% in ejection fraction, 31% in VCF and 39% in dp/dt max, while LVEDP decreased to normal values as if at resting conditions. All changes were significant (P less than 0.05). 4. LV-systolic pressure and end diastolic volume (P greater than 0.05) remained the same. Thus the AR-L 115-induced improved LV-pump function was accomplished under stress conditions in the absence of evidence for myocardial ischaemia.

Adult↗
PubMedDate not supplied

The pyruvate kinase isoenzyme tumor M2 (Tu M2-PK) as a tumor marker for renal carcinoma.

Various isoforms of the glycolytic enzyme pyruvate kinase are expressed in different cell-types. One of these isoforms, the type Tu M2-PK, is strongly overexpressed by tumor cells and released into body fluids. The concentration of Tu M2-PK in body fluids can be quantitatively determined by a commercially available enzyme-linked immunosorbent assay (ELISA)-kit. Using this kit, the Tu M2-PK concentration was measured in EDTA-plasma of 64 patients with renal carcinoma and 10 patients suffering from nephritis. The ranges of the Tu M2-PK-concentrations of the two groups did not overlap, indicating a highly significant discrimination of renal carcinoma and benign renal diseases. Furthermore, the Tu M2-PK-concentration in EDTA-plasma correlates strongly with the Robson tumor stage of the 64 patients. The present results indicate that the Tu M2-PK might be the first tumor marker which could be an excellent complementation of the diagnostic program for renal carcinoma.

Biomarkers, Tumor↗
PubMedDate not supplied

Value of tumor M2 (Tu M2-PK) in patients with renal carcinoma.

Pyruvate kinase is one of the glycolytic key enzymes. It exists in various isoforms which are expressed in different cell types. One of these isoforms, the type Tu M2-PK, is strongly overexpressed by tumor cells and released into body fluids. The concentration of Tu M2-PK in body fluids can be quantitatively determined by a commercially available enzyme-linked immunosorbent assay (ELISA)-kit. The Tu M2-PK concentration was measured in EDTA-plasma of 116 patients with renal carcinoma and 42 patients suffering from nephritis, by using this kit. The ranges of the Tu M2-PK-concentrations of the two groups did not overlap, indicating a highly significant discrimination of renal carcinoma and benign renal diseases. Furthermore, the Tu M2-PK concentration in EDTA-plasma correlated strongly with the Robson tumor stage of the 116 patients. The present results indicated that the Tu M2-PK might be the first tumor marker, which could be an excellent complementation of the diagnostic program for renal carcinoma.

Biomarkers, Tumor↗
PubMedDate not supplied

Comparative efficacy of the new cardiotonic agent DPI 201-106 versus dobutamine in dilated cardiomyopathy: analysis by serial pressure/volume relations and "on-line" MVO2 assessment.

DPI 201-106 (DPI) as a positive inotropic drug might be useful in treating dilated cardiomyopathy (DCM). In seven DCM patients with normal (group A) and eight DCM patients with abnormal (group B) left ventricular (LV) function, we analyzed serially (computer-assisted) pressure/volume (P/V) effects as P/V loops (microtip catheter/99mTc scintigraphy) using DPI (30 micrograms/kg X min i.v.) and dobutamine (DOB) (10 micrograms/kg X min i.v.) for quantitative comparison of hemodynamic effects. Contractility (dP/dtmax) improvement was greater with DPI (group A, +23%; group B, +47%) than with DOB (group A, +21%; group B, +32%), as was the simultaneous LV end-diastolic pressure decrease--DPI (group A, -39%; group B, -42%) versus DOB (group A, -21%; group B, -18%). LV efficiency increased with DPI (group A, +22%; group B, +55%), but myocardial oxygen consumption (MVO2) did not change significantly. Five of 15 patients showed an increase in dP/dtmax with DPI only; with DPI there were fewer "nonresponders" than with DOB. Thus, DPI increases contractility in DCM hearts while reducing preload rather than causing higher metabolic costs. Such beneficial hemodynamic effects appear to be stronger in the more impaired myocardium (group B patients) and quantitatively superior to those induced by DOB. This might indicate that residual myocardial reserves are more readily accessible to the influences of DPI than to those of DOB. Serial P/V loops and MVO2 assessment aided the demonstration of DPI's efficacy in a more complex way.

Adult↗
PubMedDate not supplied

Cardiac glycoside receptors in clinical and experimental states of chronic renal failure.

To investigate the mechanisms leading to decreased cardiac glycoside sensitivity in uremia, digitalis receptors were characterized by [3H]-ouabain binding to mononuclear leucocytes of chronically hemodialyzed patients and to cerebral cortex membranes of partially nephrectomized rats. There were no statistically significant differences in receptor density and affinity between uremic patients and healthy control persons and between partially nephrectomized and sham operated rats. [3H]-Ouabain bound with high affinity to intact mononuclear leucocytes and to cerebral cortex membranes. However, the affinity to the cerebral cortex membrane preparation was markedly higher.

Animals↗
PubMedDate not supplied

Diagnostic value of skeletal AP and PSA with respect to skeletal scintigram in patients with prostatic disease.

The aim of this study was to compare the diagnostic value of skeletal AP and PSA with the skeletal scintigram in patients with prostatic cancer. PSA and skeletal AP were measured by Tandem-R-Ostase Assay (IRMA) and Tandem-R-PSA-Assay. 64 patients with prostatic cancer, 20 of them in stage D2 were involved. Patients with a prostatic cancer and bone metastases show remarkable increased skeletal AP concentration with a median concentration of 50ng/ml SAP and 95 ng/ml PSA. Patients without bone metastases have a lower median concentration of SAP at 10 ng/ml and PSA concentration of 40 ng/ml which is within the normal range. Six out of 20 patients at stage D2 showed a significant increase of SAP concentration and even of PSA before bone metastases were seen by skeletal scintigraphy. We conclude when skeletal metastases are assumed in patients with prostatic cancer, a combination of skeletal scintigramm and measurement of SAP seem to be of advantage to recognize patients with bone metastases earlier.

Alkaline Phosphatase↗