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Biomedical subjects

B Müller

Publications and source records attributed to B Müller.

At least 19 recordsLinked to original sources
PubMed2001

Brinker requires two corepressors for maximal and versatile repression in Dpp signalling.

decapentaplegic (dpp) encodes a Drosophila transforming growth factor-beta homologue that functions as a morphogen in the developing embryo and in adult appendage formation. In the wing imaginal disc, a Dpp gradient governs patterning along the anteroposterior axis by inducing regional expression of diverse genes in a concentration-dependent manner. Recent studies show that responses to graded Dpp activity also require an input from a complementary and opposing gradient of Brinker (Brk), a transcriptional repressor protein encoded by a Dpp target gene. Here we show that Brk harbours a functional and transferable repression domain, through which it recruits the corepressors Groucho and CtBP. By analysing transcriptional outcomes arising from the genetic removal of these corepressors, and by ectopically expressing Brk variants in the embryo, we demonstrate that these corepressors are alternatively used by Brk for repressing some Dpp-responsive genes, whereas for repressing other distinct target genes they are not required. Our results show that Brk utilizes multiple means to repress its endogenous target genes, allowing repression of a multitude of complex Dpp target promoters.

Alcohol Oxidoreductases↗
PubMed2001

Purified U7 snRNPs lack the Sm proteins D1 and D2 but contain Lsm10, a new 14 kDa Sm D1-like protein.

U7 snRNPs were isolated from HeLa cells by biochemical fractionation, followed by affinity purification with a biotinylated oligonucleotide complementary to U7 snRNA. Purified U7 snRNPs lack the Sm proteins D1 and D2, but contain additional polypeptides of 14, 50 and 70 kDa. Microsequencing identified the 14 kDa polypeptide as a new Sm-like protein related to Sm D1 and D3. Like U7 snRNA, this protein, named Lsm10, is enriched in Cajal bodies of the cell nucleus. Its incorporation into U7 snRNPs is largely dictated by the special Sm binding site of U7 snRNA. This novel type of Sm complex, composed of both conventional Sm proteins and the Sm-like Lsm10, is most likely to be important for U7 snRNP function and subcellular localization.

Amino Acid Sequence↗
PubMed2001

Conditioned blocking and schizophrenia: a replication and study of the role of symptoms, age, onset-age of psychosis and illness-duration.

Measures of selective attention processing like latent inhibition (LI) and conditioned blocking (CB) are disturbed in some patients with schizophrenia. [LI is the delay in learning about the associations of a stimulus that has been associated with no event (versus de novo learning); CB is the delay in learning the associations of a stimulus-component when the other component has already started to acquire these associations.] We proposed: (1) to replicate the reported decreases of CB in patients without paranoid-hallucinatory symptoms; (2) to see if CB depends on the age of illness-onset and its duration, as reported for LI. We studied 101 young and old, acute and chronically ill patients with schizophrenia, of whom 62 learned a modified 'mouse-in-house' CB task, and compared them with 62 healthy controls matched for age, education and socio-economic background. CB was more evident in patients with a diagnosis of paranoid schizophrenia than other subtypes. An unusual persistence of high CB scores through testing was associated with productive symptoms (including positive thought disorder). Reduced CB related to the expression of (a) Schneider's first rank symptoms of ideas-of-reference and (b) to negative symptoms like poor rapport and poor attention. CB was less evident in the older patients and those with an earlier illness-onset. In contrast to the similar LI test of selective attention, CB is found in patients with paranoid schizophrenia and its expression is not related closely to illness duration. This implies that the two tests reflect the activity of different underlying processes. We suggest that reduced CB on initial test-trials in nonparanoid schizophrenia reflects the unusual persistence of controlled information processing strategies that would normally become automatic during conditioning. In contrast, continued CB during testing reflects an unusual persistence of automatic processing strategies.

Acute Disease↗
PubMed2001

Macroprolactinaemia, the major unknown in the differential diagnosis of hyperprolactinaemia.

We report on 10 cases of macroprolactinaemia and discuss recent evidence that many patients with hyperprolactinaemia (8-26%, depending on the population studied) have in fact normal amounts of circulating prolactin but false-high values in commercial assays. This is caused by macromolecular prolactin (also named big-big prolactin or macroprolactin), a complex of prolactin with IgG antibodies leading to apparent hyperprolactinaemia. In spite of the expanding literature on this topic, it remains an underrecognised problem, typically causing unnecessary procedures such as laboratory controls, MRI of the pituitary, treatment with dopamine agonists or even pituitary surgery. Physicians involved with diagnosis and treatment of hyperprolactinaemia (general practitioners, gynaecologists, neurosurgeons, endocrinologists and biochemists) should suspect the presence of apparent hyperprolactinaemia in any patient with a high prolactin value but no related symptoms. Medical laboratories should be aware that their prolactin assay can interfere with macroprolactin and should implement the use of the PEG precipitation test in the work-up of hyperprolactinaemia, a simple and effective means of correctly diagnosing apparent hyperprolactinaemia.

Adolescent↗
PubMed2001

A method to obtain right-side-out and sealed plasma membrane vesicles from the filamentous fungus Penicillium simplicissimum.

Plasma membrane vesicles were purified from the citrate excreting filamentous fungus Penicillium simplicissimum. The hyphae were disrupted by grinding in a glass bead mill and plasma membranes were obtained from a crude membrane fraction by partitioning in an aqueous dextran/polyethylene glycol two-phase system. The resulting enriched plasma membrane fraction contained only minor contaminations of marker enzymes of intracellular membranes, consisted of more than 90% of right-side-out vesicles and was sealed for potassium.

Cell Fractionation↗
PubMed2001

[Surgical treatment of femoral neck pseudarthrosis associated with delayed union of ipsilateral femoral shaft fracture].

A femoral neck fracture combined with an ipsilateral shaft fracture is often primarily not diagnosed. The later treatment is technically more difficult, because in the choice of operative technique for the shaft fracture the neck fracture it was not considered. In this case report the treatment of the shaft fracture with a reamed nail, and the secondary stabilisation of the femoral neck fracture with screws resulted in a pseudarthrosis of the femoral neck with an unfavourable inclination of the fracture plane. Both fractures healed without complications after changing the nail against a bridging plate and an intertrochanteric osteotomy with correction in two planes.

Adult↗
PubMed2001

World Stress Map of the Earth: a key to tectonic processes and technological applications.

Modern civilisation explores and penetrates the interior of the Earth's crust, recovers from it and stores into it solids, fluids and gases to a hitherto unprecedented degree. Management of underground structures such as boreholes or reservoirs take into account the existing stress either to take advantage of it or at least to minimise the effects of man-made stress. This paper presents the World Map of Tectonic Stresses (in short: World Stress Map or WSM) as a fundamental geophysical data-base. The impact of the WSM is pointed out: in the context of global tectonics, in seismic hazard quantification and in a wide range of technological problems in industrial applications such as oil reservoir management and stability of underground openings (tunnels, boreholes and waste disposal sites).

Earth, Planet↗
PubMed2001

Knee laxity after ACL reconstruction with a BPTB graft.

UNLABELLED: The objective of the study was to compare prospectively short-term and mid-term results after ACL reconstruction with special focus on changes in instrumented knee laxity. METHODS: The original study group included prospectively 58 patients who underwent arthroscopically assisted ACL reconstruction with BPTB graft in a two-tunnel technique between 1991 and 1993. Seven patients were lost to follow-up, leaving 51 patients for a first follow-up at 6 months and a second follow-up at 3-6 years (mean 4.3 years). Clinical results were evaluated by means of the Lysholm score and the IKDC score. Laxity was assessed using a KT-1000 arthrometer applying an 89 N anterior load in 20 degrees of flexion. Increased laxity was defined as a 3 mm increase in AP translation between the first and the second follow-up. RESULTS: At mid-term follow-up pivot shift was negative in 86% of cases. IKDC score: normal = 28%, nearly normal = 44%, abnormal = 24%, severely abnormal = 4%. KT-1000: < 3 mm = 68%, 3-5 mm = 24%, > 5 mm = 8%. The mean KT-1000 side-to-side difference was 1.08 (0.17) mm at 6 months and 2.01 (0.29) mm at 3-6 years. The difference was statistically significant (P < 0.005). According to the defined criteria, seven patients had increased laxity at the second follow-up, suggesting a malfunction of the graft due to stretch-out or injury. In this subgroup the mean KT-1000 measurements were 0.86 (0.26) mm at the first follow-up and 5.93 (0.54) mm at the second follow-up. In five of these patients, a malposition of the tunnels was identified as a possible cause. In the remaining group, KT-1000 measurements did not differ significantly between the first and the second follow-up [1.12 (0.20) mm versus 1.37 (0.21) mm]. CONCLUSIONS: Increase in AP laxity occurred in 14% of our cases between the first and the second follow-up. In most of these cases increased laxity was due to inadequate surgical technique, especially malposition of bony tunnels. If tunnel position was correct, there was no evidence for elongation of grafts over time as a general principle.

Adult↗
PubMed2001

Interfacing a silicon chip to pairs of snail neurons connected by electrical synapses.

Future hybrid neuron-semiconductor chips will consist of complex neural networks that are directly interfaced to electronic integrated circuits. They will help us to understand the dynamics of neuronal networks and may lead to novel computational facilities. Here we report on an elementary step towards such neurochips. We designed and fabricated a silicon chip for multiple two-way interfacing, and cultured on it pairs of neurons from the pedal ganglia of the snail Lymnaea stagnalis. These neurons were joined to each other by an electrical synapse, and to the chip by a capacitive stimulator and a recording transistor. We obtained a set of neuroelectronic units with sequential and parallel signal transmission through the neuron-silicon interface and the synapse, with a bidirectionally interfaced neuron-pair and with a signal path from the chip through a synaptically connected neuron pair back to the chip. The prospects for assembling more involved hybrid networks on the basis of these neuroelectronic units are considered.

Animals↗
PubMed2001

Long-term outcome and prognosis of obsessive-compulsive disorder with onset in childhood or adolescence.

The aim of the catch-up follow-up study is to describe the long-term outcome of obsessive-compulsive disorder (OCD) with onset in childhood and adolescence. The psychiatric morbidity in adulthood including personality disorders was assessed and predictors in childhood for the course of obsessive-compulsive symptoms were examined. The total study group consisted of the entire patient population treated for OCD at our departments for child and adolescent psychiatry between 1980 and 1991. We reassessed 55 patients personally by way of structured interviews. The mean age of onset of OCD was 12.5 years and the mean follow-up time was 11.2 years. At the follow-up investigation 71% of the patients met the criteria for some form of psychiatric disorder, while 36% were still suffering from OCD. Of the patients with a present diagnosis of OCD 70% had at least one further clinical disorder (especially anxiety and affective disorders). The most frequent personality disorders diagnosed were obsessive-compulsive (25.5%), avoidant (21.8%), and paranoid (12.7%) personality disorders. In-patient treatment, terminating treatment against advice and tics in childhood or adolescence significantly correlated with more severe OC symptoms in adulthood.

Adolescent↗
PubMed2001

Pharmacogenetics: a new diagnostic tool in the management of antidepressive drug therapy.

Pharmacogenetics studies the genetic basis of an individual's ability to respond to pharmacotherapy. Variability of this response is a major problem. Fatal adverse drug reactions have been reported to be the fourth leading cause of death in the US. In depression, 30-40% of all patients do not respond sufficiently to the initial treatment and it can take up to 6 weeks for them to be identified. Much knowledge has been gathered throughout the last 3 decades about the genetic basis of pharmacokinetic variability. Genetic tests suitable for the routine laboratory are now available for some important metabolizing enzymes (e.g., CYP2D6, CYP2C19) identifying those individuals who are slow or fast metabolizers of certain drugs, many of which are widely used in the treatment of depression (e.g., tricyclic antidepressants). The possible use of these tests in the clinical practice of monitoring antidepressant therapy is discussed in relation to older phenotyping methods and therapeutic drug monitoring.Less well studied than the genetics of pharmacokinetics is the genetic basis of pharmacodynamic variability. As selective serotonin reuptake inhibitors (SSRI) have a wide therapeutic index, pharmacokinetic variability usually does not explain insufficient response to therapy. Recently, some excitement was caused by reports on serotonin transporter gene polymorphisms and their influence on the response to antidepressive therapy with SSRIs as this could provide an interesting diagnostic tool in assessing the chances of response to the most popular group of antidepressants at present. Current knowledge in this young field of research is summarized.

Antidepressive Agents↗
PubMed2001

The Henry's law coefficient of 2-nitrophenol over the temperature range 278-303 K.

Although 2-nitrophenol has been identified as an important environmental chemical there is scarcity in the literature regarding the temperature dependence of its Henry's law coefficient, H. Here a bubble purge method was used to measure H for 2-nitrophenol over the temperature range 278-303 K. A novel approach in the data treatment allowed correction of the data for non-equilibrium partitioning in the apparatus to obtain the true equilibrium H value. The experimentally derived temperature-dependent expression for H of 2-nitrophenol is lnH (M atm(-1)) = (6290/T (K)) - 16.6. The standard enthalpy and entropy of gas-to-liquid transfer for 2-nitrophenol in aqueous solution are -52.3 +/- 8.1 kJ mol(-1) and -138 +/- 28 J mol(-1) K(-1), respectively. (Errors are 95% confidence intervals.)

Chemical Phenomena↗
PubMed2001

Protein adsorption and monocyte activation on germanium nanopyramids.

Germanium can form defect-free pyramidal islands on Si(1 0 0)-2 x 1 with a height of 15 nm and a width of 60 nm. Using chemical vapor deposition we have prepared substrates with different nanopyramid densities to study the impact on contact angles, protein adsorption and cell behavior. The advancing contact angle of a water droplet of millimeter size significantly raises with nanopyramid density. The dynamic contact angle measurements reveal that the substrate surface is highly hydrophilic. On such a surface the adsorption of hydrophilic proteins, i.e. albumin and globulin, is drastically increased by the presence of nanopyramids. More important, however, the globulin is inactive after adsorption on nanopyramid edges. This observation is supported by the cytokine release of IL-1beta and TNF-alpha of monocyte-like cell line U937. Consequently, the presence of nanopyramidal structures gives rise to less inflammatory reactions.

Adsorption↗
PubMed2001

The stiffness of bone marrow cell-knit composites is increased during mechanical load.

A novel device for mechanical stimulation of primary adult rat bone marrow cells cultured on three-dimensional knitted textiles has been prototyped. A method has been developed ensuring a well-defined, high-density, and reproducible cell seeding on the knitted fabric. After culturing for 18-52 days the cell-knit composites were subjected to uniaxial 2% stretching and relaxation. The frequency was altered between 0.1 Hz (196 min, loading phase) and 0.01 Hz (360 min, resting phase). Identically treated knits without cells exhibited a slight stiffness reduction, whereas the stiffness of knits with cells increased from cycle to cycle. The stiffness increase was found to depend on the duration of the culture period before mechanical loading. Our data suggest that the extracellular matrix deposited by the cells on the knit and intact microtubuli of living cells cause the observed stiffness increase. In comparison to the unstrained static cell-knit composites cell proliferation and bone cell differentiation were reduced by the mechanical load.

Animals↗
PubMed2001

TP53 gene mutations, nuclear p53 accumulation, expression of Waf/p21, Bcl-2, and CD95 (APO-1/Fas) proteins are not prognostic factors in de novo glioblastoma multiforme.

Glioblastoma multiforme (WHO grade IV; GBM) is the most common primary brain tumor with a median survival of less than one year despite multimodal treatment regimens. However, a small subgroup of GBM patients has a better clinical outcome, with a small number of patients surviving several years. Apoptosis, a genetically determined program of cell suicide, may be induced as a consequence of critical DNA damage. However, due to defects in the signaling pathways, cancer cells may escape apoptosis, despite carrying irreversible DNA damage. In the present study, we have analyzed tumors of two age-matched, equally treated groups of GBM patients with different postoperative time to tumor progression (TTP), defined as 'short-term' for TTP of less than 6 months (n = 54), and 'long-term' for TTP of more than 12 months (n = 39) for alterations in apoptosis regulatory pathways: Mutations of the TP53 tumor suppressor gene and/or nuclear accumulation of its gene product p53, expression of Waf/p21, CD95 (Apo1/Fas), and Bcl-2. TP53 mutations were found in 12 out of 54 (22%) GBMs of short-term survivors and 8 out of 35 (23%) tumors of long-term survivors; the respective numbers for nuclear p53 protein accumulation were 12/53 (23%) and 10/37 (27%). Waf1/p21 expression was found in 13/53 (25%) tumors of short-term survivors and 9/35 (26%) GBMs of long-term survivors. The respective numbers for Bcl-2 expression were 25/42 (60%) and 22/36 (61%) and for CD95 (Apo1/Fas) expression 20/49 (41%) and 14/36 (39%) GBMs. The percentage of alterations in genes/proteins involved in the apoptotic pathway investigated here was virtually identical in the two groups of clinically different GBM patients. Thus, our data imply that none of these alterations investigated per se has a strong impact on the overall survival of GBM patients.

Adult↗