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Biomedical subjects

W A Knorre

Publications and source records attributed to W A Knorre.

At least 19 recordsLinked to original sources
PubMed2000

Antibiotica research in Jena from penicillin and nourseothricin to interferon.

Milestones of antibiotics research and biotechnology in Jena/Thuringia are: 1938--Hans Knöll established a strain collection of microorganisms; 1942--production of penicillin on laboratory scale by Hans Knöll; since 1945--development of industrial production processes for penicillin and streptomycin; 1952--production of BCG-vaccine; since 1956--development of biotechnical processes in the Institute of Microbiology and Experimental Therapy for actinomycin C, oxytetracyclin, erythromycin, paromomycin, turimycin, griseofulvin, nystatin, and nourseothricin, and in the 1980s for streptokinase, staphylokinase, and interferons. After the German unification the Hans-Knöll-Institute for Natural Products Research was founded.

Academies and Institutes↗
PubMed1998

Analysis and simulation of complex interactions during dynamic microfiltration of Escherichia coli suspensions.

Microfiltration is an important unit operation in downstream processing. However, due to the influence of membrane fouling, prediction of the filtration performance for biological suspensions is difficult. This paper describes a modeling approach that allows a comprehensive description of filtration performance. On the basis of experimental data and linguistic information, a specific artificial neural network was developed that predicts the process behavior within a certain range of parameters. This approach allows us to analyze influences of fermentation on filtration. By using extensive simulations, the interactions of 17 parameters were examined and the fouling causes determined. The model was developed for cell harvesting of Escherichia coli through a shear-enhanced module. The method can be applied to any cross-flow filtration process.

Bacteriological Techniques↗
PubMed1991

High cell density fermentation of recombinant Escherichia coli with computer-controlled optimal growth rate.

In recent years recombinant DNA technology has enabled us to produce various proteins of therapeutic importance with microorganisms. As an appropriate host organism, E. coli plays a dominant role. Yields of E. coli dry cell mass in shaker flask culture range from 1-2 g/L, whereas in fermentors up to 10 g dry cells/L can be achieved. ZIMET and GBF have developed a high cell density fermentation process that produces E. coli (on a glucose/mineral salt medium) up to more than 100 g dry cells/L in a special fed-batch mode. This cultivation strategy prevents oxygen limitation and hence the accumulation of acetate and other metabolic byproducts. The specific growth rate can be adjusted so that product formation reaches its optimum value. An example of the production of alpha1-interferon is presented. The high cell density fermentations were realized in 30- and 450-L Chemap fermentors (ZIMET) and in a three-stage bioreactor scale-up system (72, 300, and 1,500 L) developed in cooperation with GBF and B. Braun Melsungen AG. Multiloop controllers were used to control the process variables.

Biotechnology↗
PubMed1991

High cell density cultivation of Escherichia coli at controlled specific growth rate.

A high cell density cultivation (HCDC) for growth of Escherichia coli in an especially designed glucose/mineral salt medium is proposed. The HCDC essentially starts as a batch process which is followed by a two-phase fed-batch cultivation. After unlimited growth at mu max = 0.45 h-1 in the batch part, growth was controlled at a reduced specific growth rate (mu = 0.11 h-1 less than mu max) over a period of 3 doubling times in which the biomass concentration increased from 12 to 95 g 1(-1) (phase 1 of fed-batch cultivation). Control of growth (mu) was realized by a PO2 control loop (by variation of glucose feeding) and a mu control loop (by variation of agitation speed N) while the actual mu was calculated from the off-gas composition. If the agitation rate cannot be increased anymore the mu controller is switched off (end of phase 1). In the following phase 2, mu declines, however, the still acting pO2 (glucose) controller guarantees sufficient O2 supply till the end of the cultivation with a biomass concentration of 110 g 1(-1) (dry mass). The proposed HCDC suppresses generation of inhibitory by-products and the high yield coefficients indicate the economy of the process.

Bacteriological Techniques↗
PubMed1990

High cell density fermentation of recombinant Escherichia coli expressing human interferon alpha 1.

A defined medium was developed which, by means of a specific fed-batch mode, allows growth of the recombinant Escherichia coli strain TG1 (pBB210) up to a cell density of 60 g dry weight/l. Apart from glucose and aqueous ammonia fed as carbon and nitrogen sources, it was necessary to supply other nutrients or O2-enriched air. Aqueous ammonia also served for pH control. The pO2 level was kept at 20% saturation via closed-loop controls operating the two output variables of stirrer speed and glucose feeding rate. This fed-batch method prevented significant accumulation of acetate and other metabolic by-products. The recombinant E. coli expressed interferon alpha 1 more efficiently at a lower specific growth rate (muPr approximately 0.15 h-1) than at the maximum specific growth rate (mu max = 0.45 h-1). Therefore, fermentation in the batch phase at mu max was only allowed to continue up to a medium cell density. In the succeeding fed-batch phase, the specific growth rate was reduced to muPr by increasing the stirrer speed according to an empirically developed time scale.

Ammonia↗
PubMed1988

[Changes in the pharmacokinetics of gentamycin during nephrotoxic therapy].

Nephrotoxicity secondary to aminoglycoside antibiotic therapy is a well-known complication in clinical medicine. We have analysed the influence of a 10-day gentamicin treatment with 3.40 mg/d on pharmacokinetic parameters and renal excretion of electrolyses and beta-NAG in 10 patients (9 female, 1 males) with UTJ. Using compartment-independent methods the following kinetic parameters at the first and 10th day of treatment were estimated: total body clearance from 100 to 80 ml/min (-20%), mean residence time from 2.7 to 3.5 h (+28%) and AUC from 6.7 to 9.4 mg/l.h (+41%). Similar results could be obtained using a linear two-compartment model: k13 is changed from 0.74 to 0.54 h-1 (-27%). Vdss approximately 16 1, k12 and k21 are not significantly influenced. There was no significant difference between the first and 10th day for renal excretion electrolyses, urine volume and osmolality with the exception of beta-NAG, which increased from 7.2 to 11.7 U/l (p less than 0.05). From the results it can be concluded that even a ten day gentamicin treatment with normal doses and serum concentrations in the therapeutic range less than 5 mg/l induce nephrotoxic effects at the glomerular and tubular side of the nephron. For quantification of the nephrotoxic effects we propose a nonlinear two-compartment model with a new pharmacokinetic parameter for renal damage. This new model allows to predict and to compare the nephrotoxic effects for different aminoglycoside antibiotics and different modes of treatment.

Electrolytes↗
PubMed1985

Two-pool model analysis of data in hemodialysis by means of programmable pocket calculator TI 59.

Four parameters of a two-pool model are evaluated by an iterative method using the explicit solutions of the linear differential equations. For this it was presumed that the residual renal clearance is sufficiently small. Five data pairs of measured plasma concentrations ci for the time points ti (i = 0 to 4), as well as the dialyzer and residual renal clearances (KD and KR), must be given and put in the calculator. A sample run is shown for urea kinetics. The parameter estimation takes about 10 min. The program is suitable to assist in the individualization of dialysis therapy.

Computers↗
PubMed1984

Model aided dynamic process analysis and optimization for the nourseothricin fermentation.

The relation between product formation and growth kinetics could be characterized by two facts: the specific product formation rate depends on the ageing of the population and on the specific growth rate. These relation was formulated and quantified by a mathematical model, which was fitted to experimental data of a representative fermentation run und used to predict an optimal fermentation mode. In the result of this discussion cyclic fed batch fermentation was found to be optimal.

Anti-Bacterial Agents↗
PubMed1984

Dynamic model of discontinuous and continuous phaseolotoxin production of Pseudomonas syringae pv. phaseolicola.

From experimental data of kinetics of growth, glucose consumption and product formation of Pseudomonas syringae pv. phaseolicola the development and parameter estimation of a mathematical model is presented. The model describes the behaviour of both, batch and chemostat culture, as well as for different temperatures. The model is favoured for dynamic optimization studies. Maximal productivity is reached in the chemostat for a dilution rate which is only a little bit smaller than the wash out point.

Culture Media↗
PubMed1980

Bistability in a model of microbial product formation.

A mathematical model of continuous growth of microorganisms and product formation with growth inhibition by the product is presented and investigated. Two stable steady states occur due to the competion of growth and product formation for the same limiting substrate. One stable state is characterized by a high product concentration but low biomass concentration whereas the other state is characterized by the opposite relations. The first steady state is approached by oscillating kinetics. Both phenomena are consistent with frequently observed kinetic instabilities in industrial fermentation processes.

Anti-Bacterial Agents↗
PubMed1978

[Maintenance metabolism in glucose-limited chemostat cultures of Streptomyces hygroscopicus].

Investigations with the mycelium forming bacterium Streptomyces hygroscopicus IMET JA 6599 in glucose-limited chemostat cultures gave a maintenance coefficient of m = 0.031 h-1. This low maintenance coefficient corresponds to those of moulds (RIGHELATO et al. 1968, CARTER et al. 1971). With a simple model structured in active and inactive biomass (x1 and x2) it was tried to explain the low maintenance coefficient of S. hygroscopicus in relation to nonfilamentous growing microorganisms. The model contains the transition rate k, which describes the transition of active biomass in inactive one and the decay rate beta, which considers the decay of hyphae. The model was used to study the influence of beta on the maintenance coefficient and it was shown that maintenance metabolism can be simulated by the parameter beta alone.

Glucose↗
PubMed1978

[Multiphasic growth of microorganisms: modeling and computer simulation of linear growth phases].

A phenomenological and a more causal model are developed for the multiphasic discontinuous growth. The first model distinguished between the lag-phase, the exponential phase, the transient phase from the exponential to the linear phase, the linear phase, the transient phase from the linear to the stationary phase, and the stationary phase. The parameters are rate constants, critical values of biomass, and time constants. The parameters are estimated for experimental data of growth of Candida lipolytica under limitation of thiamine (Müller et al. 1978). These data are fitted also by a more causal model. This second model is in agreement with Monod's idea that a linear growth phase may be due to an enzyme or enzyme system which has a constant activity. In the analysed case of limitation of thiamine the constancy of the dehydrogenase activity is caused by a constant level of the coenzymethiaminepyrophosphate. Thus, when such a thiamine requiring enzymatic step becomes to the "bottle-neck", bacterial culture switches over from exponential to linear growth. The end of linear phase is discussed more hypothetically by the high cooperativity of activity of dehydrogenases and the existence of a mimimal specific growth rate. The results of modeling and parameter estimation are compared with experimental data of C. lipolytica. These two models are able to interpret the growth kinetic of these multiphasic growth.

Candida↗
PubMed1978

Kinetics of growth and substrate consumption of Escherichia coli ML 30 on two carbon sources.

When E. coli ML 30 is grown in batch culture on a mineral salt medium containing a mixed carbon source of glucose and pyruvate, there is no sequential utilization of the carbon sources. The consumption of glucose and pyruvate takes place simultaneously with reciprocal influence (inhibition) on rates of substrate uptake. The specific growth rate is greater than mupmax for pyruvate but smaller than musmax for glucose. In the paper three cases of kinetics of growth and of substrate consumption at several combinations of initial substrate concentrations are considered. A mathematical model is proposed and investigated. The model allows to describe the growth on glucose or on pyruvate not only as singular carbon sources, but also as a mixed carbon source with reciprocal inhibition on rates of substrate uptake. By data fitting parameters of growth and substrate consumption were found.

Escherichia coli↗
PubMed1977

A mathematical model of microbial growth including an intermediate. I. Growth in batch cultures.

A mathematical model of microbial growth is presented and examined which, in contrast to the well-known MONOD model, includes transitions from one cell "bottle-neck" to another. This is achieved by introducing an intermediate product in the model. Three variants of the model for different regulatory functions of the intermediate are considered. The results permit to describe a set of experimentally observable microbial growth curves. According to the model, the shape of the growth curves, the kinetics of substrate consumption and changes of intermediate concentration depend on culture prehistory and the nature of the intermediate regulatory function.

Bacteria↗