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Biomedical subjects

R Menzel

Publications and source records attributed to R Menzel.

At least 19 recordsLinked to original sources

The spectral input systems of hymenopteran insects and their receptor-based colour vision.

Spectral sensitivity functions S(lambda) of single photoreceptor cells in 43 different hymenopteran species were measured intracellularly with the fast spectral scan method. The distribution of maximal sensitivity values (lambda max) shows 3 major peaks at 340 nm, 430 nm and 535 nm and a small peak at 600 nm. Predictions about the colour vision systems of the different hymenopteran species are derived from the spectral sensitivities by application of a receptor model of colour vision and a model of two colour opponent channels. Most of the species have a trichromatic colour vision system. Although the S(lambda) functions are quite similar, the predicted colour discriminability curves differ in their relative height of best discriminability in the UV-blue or blue-green area of the spectrum, indicating that relatively small differences in the S(lambda) functions may have considerable effects on colour discriminability. Four of the hymenopteran insects tested contain an additional R-receptor with maximal sensitivity around 600 nm. The R-receptor of the solitary bee Callonychium petuniae is based on a pigment (P596) with a long lambda max, whereas in the sawfly Tenthredo campestris the G-receptor appears to act as filter to a pigment (P570), shifting its lambda max value to a longer wavelength and narrowing its bandwidth. Evolutionary and life history constraints (e.g. phylogenetic relatedness, social or solitary life, general or specialized feeding behaviour) appear to have no effect on the S(lambda) functions. The only effect is found in UV receptors, for which lambda max values at longer wavelengths are found in bees flying predominantly within the forest.

Animals

Opponent colour coding is a universal strategy to evaluate the photoreceptor inputs in Hymenoptera.

Behavioural tests were carried out with 9 hymenopteran insect species, which ranked certain sets of coloured stimuli according to their subjective similarity to a previously memorized stimulus. Kendall's tau co-efficient is employed for the analysis of correlation between these similarity rankings and the colour distance rankings predicted by various models of neural colour computation. The models are based on the measured spectral sensitivities of photoreceptor colour types and use a variety of simple colour coding systems to derive hypothetical colour distances. The correlation between the predictions of the models and the behavioural results serves as a measure for the likelihood of existence of a colour coding system. In all species, the similarity rankings can be best explained by assuming that colour is coded on a perceptual level by two colour opponent mechanisms. Brightness differences are ignored, indicating that an intensity-coding sub-system is not used in colour discrimination by the insects investigated. The weighting factors of the colour opponent mechanisms differ between species in detail, but not in the principles involved. It is thus possible to employ a standard measure of perceptual colour distance (colour hexagon distance) to predict the capacities of colour discrimination adequately in all the tested insects.

Agonistic Behavior

Inhibition of DNA gyrase activity in an in vitro transcription-translation system stimulates gyrA expression in a DNA concentration dependent manner. Evidence for the involvement of factors which may be titrated.

Stimulation of gyrA expression in an in vitro transcription-translation system by novobiocin, a DNA gyrase inhibitor, depends on the DNA concentration in the extract. At low DNA concentrations (less than 20 micrograms/ml) we note significant stimulation (2 to 25 x) upon the addition of novobiocin; at high DNA concentrations, stimulation is minimal. This observation is not due to the limited capacity of the system to transcribe or relax DNA. Using an extract prepared from a novobiocin-resistant strain of Escherichia coli, we were able to show that DNA gyrase mediates the novobiocin-enhanced expression. In an experiment with a fixed level of a gyrA-lac template, we found that the addition of a second non-Lac template increased expression from the gyrA-lac template, while concomitantly decreasing the extent of novobiocin stimulation. These observations are consistent with an inhibitory factor that can be titrated by increasing the DNA concentration and whose effects are minimized when the DNA template is in a relaxed conformation. The results of a mixed-extract experiment using two extracts that differ in their activities and degrees of novobiocin stimulation are also consistent with an inhibitory factor that mediates the relaxation-induced stimulation of transcription.

DNA

[Nocturnal continuous subcutaneous insulin infusion--a therapeutic possibility in labile type I diabetes under exceptional conditions].

The whole-day continuous subcutaneous insulin infusion (CSII) with portable pumps in daily blood glucose autocontrol guarantees a more stabile and favourable glycaemia than multiple injections in labile type I diabetics. The success is mainly to be traced back to the continuous replacement of the basal secretion, particularly to the nocturnal fasting phase. In this study the effect on the glycaemia is investigated with exclusively nocturnal administration of the CSII under maintenance of multiple insulin injections during this day. In a group of 18 type I diabetics the nocturnal CSII in comparison to intermediate insulin administrations in the evening led to a significant improvement of glycaemia (p less than 0.01), in particular to the decrease of the fasting blood sugars (p less than 0.05). In two casuistic observations in comparison to all the other conventional methods for the compensation of the nocturnal glycaemia (depot insulin, nocturnal injection of normal insulin) the nocturnal CSII proved to be superior. Therefore, the nocturnal CSII is an--though more rarely to be used--alternative, which may be taken into consideration, of a whole-day CSII is temporarily unwished for.

Adult

"Catheter-pens"--an alternative to insulin pump treatment?

Two types of insulin pens MADI and MD, were connected to subcutaneous catheters. These "catheter-pens" were used like hand-driven insulin pumps. Results after 1 year of treatment in 30 type 1 diabetics (HCP-negative; age at onset of diabetes 16.5 +/- 1.7 years; duration of diabetes 18.5 +/- 1.6 years, on multiple insulin injections before catheter-pen application): 1. better quality of life (reduction of frequency of needle pricks, more flexibility, inconspicuous application of insulin in public); 2. daily insulin--increased number of "injections" (4.2 +/- 0.1 vs 5.8 +/- 0.1, p less than 0.01), reduction of units per kg BW (0.70 +/- 0.02 vs 0.60 +/- 0.01, p less than 0.01), reduction of intermediate-acting insulin (14.1 +/- 1.3 vs 9.2 +/- 1.2 U/d, p less than 0.05); 3. no change of HbA1 (10.8 +/- 0.8 vs 10.2 +/- 0.2%, normal range 7.7 to 8.4%), mean blood glucose (MBG) in stress situation (8.4 +/- 0.4 vs 7.7 +/- 0.3 mmol/l), serum cholesterol and body weight, both within normal range; 4. improvement (p less than 0.05) of serum triglycerides, serum HDL-cholesterol, ratio of apolipoprotein A1/B; 5. rare skin reactions at the needle site. Conclusion. Catheter-pens offer a very convenient alternative for insulin administration in intensified conventional insulin treatment with multiple injections in type 1 diabetics.

Apolipoproteins A

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