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Biomedical subjects

R Menzel

Publications and source records attributed to R Menzel.

At least 109 records · Page 6Linked to original sources

A model-based system for the individual prediction of metabolic responses to improve therapy in type I diabetes.

Despite recent achievements such as home glucose monitoring and intensified injection regimens or insulin pumps, the metabolic care in diabetic patients is still mostly insufficient. One approach of further improving the management is the application of computer-aided procedures to estimate individually the optimal regimes. To accomplish this, a model-based strategy was developed which permits the prospective assessment of the metabolic outcome. This strategy comprises the following components: (1) a validated model of the physiological glucose-insulin regulatory system; (2) a procedure for identifying the metabolic situation of a given patient in terms of the model parameters; (3) methods of estimating the pharmacokinetics of insulin and its effect on glycemia, the absorption profiles of ingested glucose equivalents, and the effect of exercise as expressed in equivalents of insulin action; (4) computer procedures of prospective simulation of glycemic profiles around the day under the influence of selected or proposed therapeutic regimes. The entire method has been validated in C-peptide negative type I diabetic patients by comparing experimental results with theoretical predictions from model-based simulations over up to one year. This model-based simulation may be applied by ambulatory patients together with their physicians as a decision-support system in selecting appropriate individually suited regimes.

Blood Glucose↗

A microtiter plate-based system for the semiautomated growth and assay of bacterial cells for beta-galactosidase activity.

The introduction of automated pipetting devices, microtiter readers, and microcomputers makes it possible to significantly increase the number of enzyme assays which can be performed as part of the analysis of a biological process. A number of difficulties must be overcome in any such integrated approach based on the microtiter plate. Among these are cell lysis, temperature control, the conversion of microtiter reader optical density values to standard 1-cm path length values, and data management. The utility of such a scheme can be extended to gene regulation and bacterial genetics studies, if bacterial cell culture techniques can be incorporated into the scheme. This paper addresses these issues in the application of a semiautomated system to the study of the induction of the gyrA promoter by treatment (of a gyrA-lac operon fusion-containing strain) with a gyrase inhibitor. This system is specific to the requirements of our studies into the modulation of gene expression by DNA relaxation. The general approach, however, can be readily adapted to other studies.

Bacteria↗

Chemical codes for the control of behaviour in arthropods.

Neuromodulators and hormones elicit and modify well-defined behaviours. Their mode of action can be studied to advantage in arthropods, where the natural releasing cells and neuronal target circuits are concisely identified. The coordinated actions of biogenic amines and peptides on both central and peripheral neural activity and metabolic processes bias the whole organism to perform a coherent behavioural routine.

Animals↗

Spectral and polarized light sensitivity of photoreceptors in the compound eye of the cricket (Gryllus bimaculatus).

Retinula cells in the compound eye of the cricket (Gryllus bimaculatus) were recorded intracellularly and stained with Lucifer yellow. Two different methods were used to determine the spectral sensitivity of these cells: a) the spectral scanning method, and b) the conventional flash method. Three spectral types, with S(lambda)-curves close to the rhodopsin-absorption functions, were found with lambda max at 332 nm (UV), 445 nm (blue) and 515 nm (green), respectively. Blue receptors were only recorded in the anatomically specialized dorsal rim area (DRA), and UV and green receptors in the dorsal region of the pigmented part of the eye, whereby green receptors were only found in the ventral eye. On the basis of these results, model calculations are presented for di- and trichromatic colour vision in the cricket. The fluorescence markings revealed green receptors whose axons project with short visual fibres to the lamina, and a UV receptor with a long visual fibre which projects through the lamina to the medulla. The blue receptors send their axons either to the lamina and medulla (long visual fibres) or only to the lamina (short visual fibres). The temporal dynamics of the three receptor types were examined. The blue receptors lack a phasic component of the receptor potential, and the time from stimulus on-set to peak potential is strongly increased compared to the UV and green receptors. Light adaptation reduces the latency to less than half of the dark adapted state. Spectral adaptation experiments revealed an 'unidirectional coupling' between UV and green receptors, and it was found that polarization sensitivity (PS) in blue cells was much higher (PS = 6.5 +/- 1.5) than that of UV (PS = 1.76 +/- 0.05) and green (2.26 +/- 0.57) receptors. The functional aspects of the three receptor types are discussed with respect to the presented physiological and morphological data.

Adaptation, Physiological↗

The unexpected antitermination of gyrA-directed transcripts is enhanced by DNA relaxation.

We show that transcription originating at the gyrA promoter of Escherichia coli is less subject to termination at the lambda Toop terminator (22% read-through) than is transcription originating from either the galOP (1% read-through) or topA (3% read-through) control regions. Furthermore, termination of the gyrA transcripts decreases (60% read-through) upon relaxation of the template DNA. We believe that events related to stimulation of transcription at the gyrA promoter by DNA relaxation are responsible for the enhanced terminator read-through.

Bacterial Proteins↗

The effect of mixing regular- and intermediate-acting insulins on their absorption and biological activity.

Many insulin-dependent diabetics are now treated with different regimens of short- and intermediate-acting insulins. The new L-insulin S.N.C. (Berlin-Chemie) is thought to be appropriate for a combination with regular insulin. We investigated whether or not absorption kinetics and biological activity changes when L-insulin S.N.C. is mixed with regular insulin S.N.C. Eight non-obese healthy male subjects were connected to the BIOSTATOR. After an overnight fast 0.1 U of insulin S.N.C. and 0.3 U per kg b.w. of L-insulin S.N.C. or Monotard MC insulin (NOVO) were administered either in a mixture or separately. Injecting L-insulin S.N.C. and insulin S.N.C. in a mixture there was some, but not a statistically significant, delay in absorption of insulin. A mixture of insulin S.N.C. and Monotard provoked a marked delay of absorption during the first two hours. To examine biological activity we used the BIOSTATOR (glucose controlled dextrose infusion system). Glucose infusion rate necessary to keep blood glucose steady state concentration was taken as a measure of insulin action. Whereas mixing of insulin S.N.C. and L-insulin S.N.C. only slightly changed the profile of biological activity, a mixture of insulin S.N.C. and Monotard has a clear-cut higher potency during the late phase when compared with separately injected insulins. Therefore, insulin S.N.C. and Monotard should not be mixed. A mixture of insulin S.N.C. and L-insulin S.N.C. is also not recommended but can be done in exceptional cases.

Absorption↗

Color constancy in the honeybee.

A multicolored display was illuminated by 3 bands of wavelengths corresponding to the maxima of the spectral sensitivities of the 3 types of photoreceptors found in the bee retina. The intensity of each band could be varied individually. The light fluxes emitted by the colored areas of the multicolored display were determined quantitatively. Free-flying honeybees were trained with sugar solution to choose one of the colored areas. The illumination was then changed in such a way that the light fluxes formerly emitted by the training area were now measured on another area. When the trained bees were tested under those conditions, they still chose the training area. The relative positions of the colored areas were changed in order to exclude learning of position. It is concluded that color vision in bees is, in a certain range, independent of the spectral content of the illumination. Model calculations show that the behavior observed in bees is consistent with the retinex theory (Land, 1977), i.e., an algorithm using long-range interactions is required to explain color constancy.

Animals↗

Pharmacokinetics and biological activity of the new intermediate-acting insulin L-SNC).

To assess pharmacokinetics and biological activity of the new L-SNC insulin (Berlin-Chemie, a low immunogenic pork insulin in neutral solution purified by chromatography) ten healthy male subjects were connected to the BIOSTATOR. After an overnight fast 0.4 U of L-SNC insulin per kg body weight were injected subcutaneously in the thigh of each individual. Plasma insulin concentrations rose gradually reaching their maximum values after 8 hours. According to C-peptide levels there was some inhibition of endogenous insulin secretion. For the evaluation of insulin action we used the closed loop system (BIOSTATOR) which was transformed in its function into a glucose controlled dextrose infusion system. The amount of glucose delivered by the BIOSTATOR in order to maintain blood glucose steady state concentrations at the "basal" level was taken as a measure of biological activity of the injected insulin. The glucose infusion rate increased after insulin administration, reaching statistical significance after 3 hr. The maximum effect of L-SNC insulin was observed between 5 and 12 hours after injection. The overall duration of action of more than 16 hours meets the increasing need for insulin in the early morning in many diabetic patients. Therefore, L-SNC insulin should be recommended for intensified conventional insulin therapy to cover the night and to prevent dawn phenomenon in insulin dependent diabetics.

Adult↗

Modulation of transcription by DNA supercoiling: a deletion analysis of the Escherichia coli gyrA and gyrB promoters.

Expression of the genes determining the subunits of Escherichia coli DNA gyrase (gyrA and gyrB) is known to be induced by relaxation of the template DNA. In this paper we report a deletion analysis of the gyrA and gyrB promoter regions. We find that a DNA sequence 20 base pairs long that includes the -10 consensus region, the transcription start point, and the first few transcribed bases is responsible for the property of induction by DNA relaxation. We propose a model for relaxation-stimulated transcription in which promoter clearance is the rate-limiting step.

Base Sequence↗

his operons of Escherichia coli and Salmonella typhimurium are regulated by DNA supercoiling.

The hisW mutations of Salmonella typhimurium are highly pleiotropic mutations that elevate his operon expression, reduce ilv gene expression, alter stable RNA metabolism, and confer defective growth properties. The hisW mutations are highly linked to a naladixic acid-resistant gyrA mutation of S. typhimurium. Multicopy recombinant plasmids containing the Escherichia coli gyrA gene are able to complement both the growth defects and the elevated his operon expression associated with the hisW mutations. We conclude that hisW mutations are alleles of the gyrA gene. The hisU1820 mutant of S. typhimurium exhibits many of the same phenotypes as hisW mutants. Several lines of evidence, including high transduction linkage to recF, suggest that hisU1820 is an allele of gyrB. Finally, well-characterized gyrA and gyrB alleles of E. coli are also his regulatory mutations. We propose that a wild-type degree of chromosomal superhelicity is required for maximal production of histidyl-tRNA and normal his operon regulation.

Alcohol Oxidoreductases↗

Fusions of the Escherichia coli gyrA and gyrB control regions to the galactokinase gene are inducible by coumermycin treatment.

We have previously shown that the genes encoding the two subunits of Escherichia coli DNA gyrase are regulated in a manner which is dependent on DNA conformation. When the DNA encoding the gyrA and gyrB genes is relaxed, both genes are expressed at a high level; in negatively supercoiled DNA they are expressed at a low level. In this paper we describe fusions of both the gyrA and gyrB 5' sequences to the E. coli galactokinase gene. In such fusions we found that galactokinase can be induced by treating the cells with coumermycin A1, an inhibitor of DNA gyrase. Our results suggest that the regulation occurs at the transcriptional level and that only a small region of DNA is necessary for coumermycin-induced gene expression.

Amino Acid Sequence↗

Marking and recording of monopolar cells in the bee lamina.

Monopolar cells in the lamina ganglionaris of the honeybee, Apis mellifera, were marked individually for the first time and intracellular recordings made. The electrophysiological responses were mainly hyperpolarizing with peaks and descending plateaux; one specific cell gave depolarizing responses, sustained in UV, and phasic at other wavelengths. Spectral sensitivity curves obtained by the spectral scanning method showed maximum sensitivity at 520 nm. Three morphological cell types were encountered, all of which differ considerably from those described by Ribi (1).

Animals↗

Serum magnesium in insulin-dependent diabetics and healthy subjects in relation to insulin secretion and glycemia during glucose-glucagon test.

UNLABELLED: In order to investigate the influence of insulin secretion on serum magnesium concentrations 33 insulin-dependent diabetics and 10 control subjects were studied. The residual insulin secretion (RIS) was investigated by measurement of human C-peptide (HCP) before and after stimulation during on OGTT (1.75 mg/kg)-glucagon (i.v. 0.1 mg glucagon/kg)-test. RESULTS: Certain RIS existed in 11 insulin-dependent diabetics, 12 were without any RIS (uncertain RIS in 10 patients). Glucose tolerance and daily glycemia differed significantly among the two groups. However, all diabetics were far from euglycemia, (3.3-9.3 mmol/l): Fasting plasma glucose 12.0 +/- 0.9 (certain RIS), 15.0 +/- 0.8 (no RIS), 13.9 +/- 1.8 (uncertain RIS). Serum magnesium was significantly lower in all diabetics, both before and during the test. There was no change during the OGTT-glucagon-test and no difference among the three groups of insulin-dependent diabetics. So, we conclude that a small RIS in our longterm insulin-dependent diabetics has no influence on the behaviour of serum magnesium. But, magnesium depletion can influence coronary blood flow, blood clotting, and atherogenesis. Therefore, it should be necessary to pay more attention to the hypomagnesemia in insulin-dependent diabetics.

Adult↗

DNA sequence and transcription of the region upstream of the E. coli gyrB gene.

We have determined the sequence of a 1498 base-pair region in E. coli that extends from within dnaN through recF and into the gyrB gene. An open reading frame of 1071 base pairs has been identified with the recF structural gene. By S1 mapping, we have located a transcription start point 31 base pairs upstream of gyrB. The amount of this transcript is much greater in cells that have been treated with novobiocin, a treatment which is known to induce greater synthesis of DNA gyrase.

Amino Acid Sequence↗

Results of treatment with continuous subcutaneous insulin infusion (CSII) in insulin-dependent (type I) diabetics.

10 labile insulin-dependent diabetic patients treated with CSII were followed up for 6 to 16 months under conditions of everyday life. The mean blood glucose (MBG), glycosylated haemoglobin (HbA1), motor nerve conduction velocity (MCV), and respiratory heart arrhythmia at rest (RHA) were investigated. A significant improvement of metabolic control was observed (MBG 8.03 +/- 1.40 vs 5.18 +/- 0.87 mmol/l, p less than 0.01; HbA1 10.7 +/- 1.3 vs 8.7 +/- 1.6%, p less than 0.05) in comparison with the control values under intensified conventional therapy. MCV increased gradually but the average RHA remained unchanged. The psychological examination employing a questionnaire reflects that all patients selected were highly motivated and that their positive attitudes were further stabilized during pump treatment. An average of three mild hypoglycaemic episodes occurred per month per patient; these were no more than under intensified conventional treatment. Other minor clinical and technical complications occurred at a total frequency of one per month per patient and did not achieve therapeutical relevance.

Adult↗