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Biomedical subjects

L Müller

Publications and source records attributed to L Müller.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Energy expenditure at rest and obesity].

Adult human body has to have, because of every day fluctuating energy intake and energy needs, very precious adaptive mechanisms for maintenance of heat homeostasis in the body and nearly stable body weight and body composition, which are optimal for life and reproduction. These short term functioning adaptive mechanisms are called "empty biochemical mechanisms", where chemically bound energy is transformed to heat without work performance. These mechanisms are present on the cellular level (substrates cycles, uncoupling of respiration chain), on the interorgan metabolic level (glycolysis and gluconeogenesis between liver and adipose tissue-glucose-lactate cycle). Central nervous system controls them via many factors; the most important are catecholamines, leptin, insulin, thyroid hormones, cortisol, growth and sex hormones. Neurotransmitters and neuronal net influence energy intake and other behavior. Obesity seems to be associated with the amelioration or overcoming of possibilities of function short-term effective adaptive mechanisms.

Adaptation, Physiological↗
PubMed1998

[Health effects of weight reduction].

Although weight loss is routinely recommended for obese person, the observational literature is controversial in respect of prolongation of life longevity after body weight loss. The positive long-term outcome has been found only in intentional weight loss in obese people with obesity-related comorbidities. The main task in obesity treatment strategy is "primum non nocere". The authors analysed the short-term effect and acceptability of low calorie diet (5 MJ) on health state of 150 obese people (BMI x = 35.9 kg/m2). The acceptability of this diet was 60% only, when the rest of patients has broken this regime mostly after second appointment with their physician. The successful patients achieved 10% weight loss from initial body weight during in average 5 months (95% CI for BMI reduction = (-4.55; -3.01), as well as reduction of percentage of body fat (95% CI = -7.7; -3). During this period has been observed in consistency with experimental evidence of other authors a decrease of plasma values of triacylglycerol, LDL cholesterol in hyperlipidemic patients, but not significant increase of HDL cholesterol. During this period obese persons have taken up more physical activities and felt themselves more psychologically comfortable.

Diet, Reducing↗
PubMed1998

[Public health relevant levels of pollutants in soil. Considerations for preventive, environmental health protection].

A working document on nation-wide applicable health-related guiding levels of environmental pollutants in soil has been prepared. These levels are intended to be the base for the administrative regulation of soil contaminations in connection with the German "Bundesbodenschutzgesetz" (Federal law on the protection of soil). Legislation demands these base levels to be intensely related to protection against serious health effects (i.e. health hazards). Looking more closely at the toxicological deduction of these values and at some values extracted from that process some uncertainties become obvious with regard to a clearcut limit between dangerous and noxious levels in soil. Indeed there are some arguments which suggest a more conservative approach. Health-care based recommendations should be introduced also at lower contaminant levels in soil. Therefore, development of an internal administrative manual on basic noxious values of soil pollutants (e.g. values below the threshold of danger) is suggested which may be useful for health authorities to cope with special problems in individual cases.

Adult↗
PubMed1998

[Compression of the ulnar nerve in Guyon's canal by a traumatic aneurysm. A case report].

A patient developed after an occupational trauma with fall on the ulnar edge of his right hand pain and swelling in the ulnar area with reduced sensation in the fourth and fifth finger. After examination performed by a neurologist, ulnar nerve-entrapment was diagnosed and operative treatment was indicated. The release of the ulnar tunnel showed a traumatic aneurysma of the ulnar artery compressing the superficial branch of the ulnar nerve. The tumor was removed and end-to-end anastomosis ensued. Four weeks after surgery, examination showed complete recovery. Various reasons of ulnar tunnel syndrome are discussed.

Adult↗
PubMed1997

Application of the in vitro rat hepatocyte micronucleus assay in genetic toxicology testing.

The investigation of micronuclei in mitogenic stimulated hepatocytes in vitro is a quite new area of research. Nevertheless, a relatively large database comprising more than 40 tested compounds of various classes has been generated up to now. This paper reviews the available data for the in vitro rat hepatocyte micronucleus assay, showing a sensitivity of this assay in identifying mutagens and genotoxic liver carcinogens of about 85%. Additionally, all of the tested non-carcinogens gave negative results. The use of primary hepatocytes instead of permanently dividing mammalian cell lines for the investigation of micronucleus induction has several advantages. (1) The broad spectrum of metabolizing enzymes expressed in primary hepatocytes ensures an adequate activation of most xenobiotics. (2) No transfer of activated metabolites via the culture medium is necessary in this system, since the metabolizing cells are the target cells themselves. (3) Whilst in experiments with permanently dividing cells the use of S9-mix restricts the treatment period with the test compounds to 2-6 h in the hepatocyte micronucleus assay continuous treatment of up to 48 h is possible. Investigations with the pyrrolizidine alkaloids retrorsine, monocrotaline and isatidine, strong mutagens and liver carcinogens, clearly showed that at least for isatidine a prolonged exposure period is essential to detect its mutagenic potential. This compound gave positive results in rat hepatocytes but not in V79-cells/S9-mix cultures. (4) The results obtained with the hepatocyte micronucleus assay are in good agreement with the genotoxic profiles of most of the compounds tested. Only three polycyclic aromatic hydrocarbons led to 'false-negative' results, since they strongly inhibited hepatocyte proliferation and thereby prevented micronucleus formation. (5) Hepatocytes are target cells of special interest when compounds are investigated which act specifically in the liver. Especially for hepatocarcinogens classified as non-genotoxins in standard genotoxicity tests or for chemicals showing DNA-repair induction in hepatocytes but no mutagenicity in standard tests, the hepatocyte micronucleus assay can contribute to clarify the situation. (6) The rat hepatocyte micronucleus assay can be performed easily and without great efforts in parallel to the in vitro hepatocyte DNA repair test (UDS-test), using the same hepatocyte batches. (7) Similar to the two versions of the UDS-test, the hepatocyte micronucleus assay can be performed following an in vivo-in vitro protocol. In order to further validate the hepatocyte micronucleus assay, as a next step controlled interlaboratory studies should be initiated.

Animals↗
PubMed1997

Bone morphogenetic protein-6 is expressed in nonparenchymal liver cells and upregulated by transforming growth factor-beta 1.

Bone morphogenetic protein-6 (BMP-6) is a member of the TGF-beta superfamily, which controls growth and differentiation during embryogenesis and acts as an osteoinductive factor in the adult organism. In order to gain further insights into the role of BMP-6, the present study analyzed the expression pattern of BMP-6 in adult rat tissues with special emphasis to the liver, since TGF-beta 1, another member of the TGF-beta superfamily, has been shown to play a fundamental role in liver physiology. Rat BMP-6-coding cDNAs were generated by homology cloning using RT-PCR and displayed 89.6 and 83.4% homology to mouse and human BMP-6, respectively. By Northern blotting BMP-6-specific transcripts 3.7 kb in size were detected in major amounts in lung and in minor quantities in spleen, kidney, heart, brain, and liver. Among the different hepatic cell populations tested BMP-6 expression was confined to nonparenchymal liver cells, namely rat hepatic stellate cells (HSC) and Kupffer cells (KC). During primary culture BMP-6 expression was increased in HSC but declined in KC. Interestingly, TGF-beta 1 stimulated BMP-6 expression of HSC especially at an early time point of culture, while interferon-gamma downregulated BMP-6 expression. The detection of BMP-6 transcripts in the liver, the cell-type-restricted expression pattern, and its regulation propose that, in addition to its osteoinductive properties, BMP-6 might play a role in liver growth and differentiation, in particular after tissue damage.

Animals↗
PubMed1997

Size principle and information theory.

The motor units of a skeletal muscle may be recruited according to different strategies. From all possible recruitment strategies nature selected the simplest one: in most actions of vertebrate skeletal muscles the recruitment of its motor units is by increasing size. This so-called size principle permits a high precision in muscle force generation since small muscle forces are produced exclusively by small motor units. Larger motor units are activated only if the total muscle force has already reached certain critical levels. We show that this recruitment by size is not only optimal in precision but also optimal in an information theoretical sense. We consider the motoneuron pool as an encoder generating a parallel binary code from a common input to that pool. The generated motoneuron code is sent down through the motoneuron axons to the muscle. We establish that an optimization of this motoneuron code with respect to its information content is equivalent to the recruitment of motor units by size. Moreover, maximal information content of the motoneuron code is equivalent to a minimal expected error in muscle force generation.

Animals↗
PubMed1997

A new method for isolation and differentiation of native Entamoeba histolytica and E. dispar cysts from fecal samples.

A new method for the purification of protozoan cysts from feces was established, allowing to isolation of native cysts. The procedure consists of two sucrose-density gradients and enzymatic digestion of cellulose particles by cellulase and can be accomplished in a few hours. The cyst fractions were differentiated into Entamoeba histolytica and E. dispar using the DNA probes P145 and B133 and a dot-blot test.

Animals↗
PubMed1997

Effect of tumour necrosis factor-alpha on proliferation, activation and protein synthesis of rat hepatic stellate cells.

BACKGROUND/AIMS: Hepatic stellate cells represent the principal matrix-synthesising cells of damaged liver and are targets of a number of cytokines currently under investigation. The study analyses the effects of tumour necrosis factor-alpha and interferon-gamma on proliferation, "activation" and protein synthesis of hepatic stellate cells. METHODS: Primary cultures of hepatic stellate cells were exposed to tumour necrosis factor-alpha and interferon-gamma. Cell proliferation was studied by 3H-thymidine and bromo-deoxy-uridine incorporation. Protein synthesis was analysed using immunoprecipitation, Western- and Northern blotting techniques. RESULTS: Proliferation of hepatic stellate cells was reduced by tumor necrosis factor-alpha and interferon-gamma, while "activation" of hepatic stellate cells as assessed by expression of smooth muscle alpha-actin and of TGF-beta/activin type I receptor was induced by tumour necrosis factor-alpha but downregulated by interferon-gamma. Tumour necrosis factor-alpha increased the synthesis of distinct extracellular matrix proteins, particularly of fibronectin and tenascin, but decreased collagen type III expression. In contrast, interferon-gamma reduced the synthesis of all connective tissue proteins tested. Among the protease inhibitors, interferon-gamma induced C1-esterase inhibitor synthesis, while tumour necrosis factor-alpha stimulated plasminogen activator inhibitor type 1 production. CONCLUSIONS: Tumour necrosis factor-alpha and interferon-gamma decrease proliferation of hepatic stellate cells, while "activation" of hepatic stellate cells and synthesis of proteins involved in matrix metabolism are regulated in a differential, cytokine-specific manner, suggesting that both cytokines play an important role in liver repair.

Adipocytes↗
PubMed1996

Expression of active streptolysin O in Escherichia coli as a maltose-binding-protein--streptolysin-O fusion protein. The N-terminal 70 amino acids are not required for hemolytic activity.

Streptolysin 0 (SLO) is the prototype of a family of cytolysins that consists of proteins which bind to cholesterol and form very large transmembrane pores. Structure/function studies on the pore-forming cytolysin SLO have been complicated by the proteolytic inactivation of a substantial portion of recombinant SLO (rSLO) expressed in Escherichia coli. To overcome this problem, translational fusions between the E. coli maltose-binding protein (MBP) gene and SLO were constructed, using the vectors pMAL-p2 and pMAL-c2. MBP-SLO fusion proteins were degraded if secreted into the E. coli periplasm, but intact, soluble MBP-SLO fusion proteins were produced at high levels in the cytoplasm. Active SLO with the expected N-terminus was separated from the MBP carrier by cleavage with factor Xa. Cleavage with plasmin or trypsin also yielded active, but slightly smaller forms of SLO. Surprisingly, uncleaved MBP-SLO was also hemolytic and cytotoxic to human fibroblasts and keratinocytes. The MBP-SLO fusion protein displayed equal activities to SLO. Sucrose density gradient analyses showed that the fusion protein assembled into polymers, and no difference in structure was discerned compared with polymers formed by native SLO. These studies show that the N-terminal 70 residues of mature (secreted) SLO are not required for pore formation and that the N-terminus of the molecule is probably not inserted into the bilayer. In addition, they provide a simple means for producing mutants for structure/function studies and highly purified SLO for use as a permeabilising reagent in cell biology research.

ATP-Binding Cassette Transporters↗
PubMed1996

Series: current issues in mutagenesis and carcinogenesis, No. 65. The genotoxicity and carcinogenicity of paracetamol: a regulatory (re)view.

The publication of several studies reporting genotoxic effects of paracetamol, one of the world's most popular over-the-counter drugs, has raised the question of regulatory action. Paracetamol does not cause gene mutations, either in bacteria or in mammalian cells. There are, however, published data giving clear evidence that paracetamol causes chromosomal damage in vitro in mammalian cells at high concentrations and indicating that similar effects occur in vivo at high dosages. Available data point to three possible mechanisms of paracetamol-induced genotoxicity: (1) inhibition of ribonucleotide reductase; (2) increase in cytosolic and intranuclear Ca2+ levels; (3) DNA damage caused by NAPQI after glutathione depletion. All mechanisms involve dose thresholds. Studies of the relationship between genotoxicity and toxic effects in the rat (induction of micronuclei in rat bone marrow including dose-response relationship, biotransformation of paracetamol at different dosages, concomitant toxicity and biochemical markers) have recently been completed. These studies, which employed doses ranging from the dose resulting in human therapeutic peak plasma levels to highly toxic doses, give convincing evidence that genotoxic effects of paracetamol appear only at dosages inducing pronounced liver and bone marrow toxicity and that the threshold level for genotoxicity is not reached at therapeutic dosage. Reliable studies on the ability of paracetamol to affect germ cell DNA are not available. However, based on the amount of drug likely to reach germ cells and the evidence of thresholds, paracetamol is not expected to cause heritable damage in man. Various old and poorly designed long-term studies of paracetamol in the mouse and rat have given equivocal results. A few of these studies showed increased incidence of liver and bladder tumours at hepatotoxic doses. National Toxicology Program (U.S.A.) feeding studies have shown that paracetamol is non-carcinogenic when given at non-hepatotoxic doses up to 300 mg/kg/d to the rat and up to 1000 mg/kg/d to the mouse. Taking into account the knowledge of the hepatotoxicity and metabolism of paracetamol and the existence of thresholds for its genotoxicity, the animal studies do not indicate a carcinogenic potential at non-hepatotoxic dose levels. Based on this updated assessment of the genotoxicity and carcinogenicity of paracetamol, it is concluded that there is no need for regulatory action.

Acetaminophen↗
PubMed1996

Transmitter concentration profiles in the synaptic cleft: an analytical model of release and diffusion.

A three-dimensional model for release and diffusion of glutamate in the synaptic cleft was developed and solved analytically. The model consists of a source function describing transmitter release from the vesicle and a diffusion function describing the spread of transmitter in the cleft. Concentration profiles of transmitter at the postsynaptic side were calculated for different transmitter concentrations in a vesicle, release scenarios, and diffusion coefficients. From the concentration profiles the receptor occupancy could be determined using alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor kinetics. It turned out that saturation of receptors and sufficiently fast currents could only be obtained if the diffusion coefficient was one order of magnitude lower than generally assumed, and if the postsynaptic receptors formed clusters with a diameter of roughly 100 nm directly opposite the release sites. Under these circumstances the gradient of the transmitter concentration at the postsynaptic membrane outside the receptor clusters was steep, with minimal cross-talk among neighboring receptor clusters. These findings suggest that for each release site a corresponding receptor aggregate exists, subdividing an individual synapse into independent functional subunits without the need for specific lateral diffusion barriers.

Animals↗
PubMed1996

Transforming growth factor beta 1-regulated gene expression of Ito cells.

During liver fibrogenesis, Ito cells are regarded as the principal matrix synthesizing cells and transforming growth factor beta 1 (TGF-beta 1) appears to be the main fibrogenic mediator. This study analyzed the effects of TGF-beta 1 on Ito cell activation, proliferation, and on the expression of a set of matrix proteins, antiproteases, and TGF-beta receptors both in "early cultured" and "culture-activated" Ito cells. Rat liver Ito cells at day 2 of primary culture ("early cultured" cells) were mainly smooth muscle alpha actin (SMA)-negative, whereas cells at day 6 were judged as "activated" cells (SMA-positive). Following 24-hour exposure to 1 ng/mL TGF-beta 1, total protein synthesis, cell proliferation, and expression of the "activation" marker SMA were not significantly changed. In addition to previously described stimulatory effects on collagen types I and III, fibronectin, undulin, and proteoglycan-gene expression, TGF-beta also dose-dependently increased synthesis and secretion of tenascin, laminin, entactin, collagen type IV, and alpha 2-macroglobulin, but decreased C1-esterase inhibitor production by Ito cells, as revealed by immunoprecipitation of endogenously labeled proteins and by Northern blot analysis. The stimulatory effect of TGF-beta was evident both in "early cultured" as well as "culture-activated" Ito cells. By reverse-transcription polymerase chain reaction (RT-PCR) analysis, TGF-beta type II, III, and TGF-beta/activin type I receptors were present in Ito cells, and their expression pattern was not changed upon TGF-beta exposure. Northern blot analysis demonstrated that type I TGF-beta/activin receptor was induced during in vitro activation and that TGF-beta exposure resulted in a slight increase of type I and III receptor messenger RNAs. In summary, the data illustrate that TGF-beta is an important fibrogenic mediator acting both on "early cultured" as well as "culture-activated" Ito cells, rather than a mitogenic or morphogenic mediator. The differential regulation of TGF-beta/activin receptors during in vitro activation and their up-regulation by TGF-beta 1 might represent a mechanism by which the receptor complex regulates TGF-beta signalling in Ito cells.

Adipocytes↗
PubMed1996

[Outcome of flexor tenolysis after injury in zone 2].

Tenolysis of flexor tendons was performed in 48 fingers of 36 patients. After a mean follow-up to ten months, the total active movement (TAM) was improved from 79 degrees preoperative to 189 degrees postoperative in 84% of the fingers with a minimal improvement of 40 degrees. Following the classification of Buck-Gramcko, 80% (38) of the fingers showed an excellent, good, or fair result. In addition, the influence of nine factors (associated injuries or procedures) on the outcome was investigated. These results showed that there is a decrease in improvement when severity of trauma increases. Arthrolysis of PIP-joint showed no negative influence on the results. We are not able to establish a predictive score for flexor tenolysis from our results.

Adolescent↗