Biomedical subjects

B Müller

Publications and source records attributed to B Müller.

At least 181 records · Page 10Linked to original sources

PubMed1998

c-myc is not useful as prognostic immunohistochemical marker in cutaneous melanoma.

BACKGROUND: Several studies indicate that immunohistochemical detection of the c-myc oncogene might serve as an additional prognostic marker in malignant melanoma. OBJECTIVE: To study c-myc expression in paraffin-embedded cutaneous melanoma and to correlate to metastatic potential and onset of metastases. METHODS: Cytoplasmic c-myc protein expression was visualized using the APAPP method, and reactivity (percent total tumor cells stained) was assessed in 62 formalin-fixed paraffin-embedded primary cutaneous melanomas (21 not metastasizing, mean Breslow 3.0 +/- 2.9 mm, 41 metastasizing, mean Breslow 3.1 +/- 3.0 mm) and 24 metastases of the same patients. RESULTS: There was no significant difference of c-myc reactivity in cutaneous melanoma who did not metastasize (n = 21, c-myc reactivity 32.7 +/- 19.3%, follow-up 10.6 +/- 1.8 years) and primaries who metastasized (n = 41, c-myc reactivity 27.7 +/- 22.4%, p = 0.29). This finding was independent of the thickness of the primary and was found within thin cutaneous melanoma with a Breslow, < 0.75 mm (range 0.24-0.65 mm, n = 20, c-myc reactivity 29.1 +/- 15.7%, p = 0.32) or within thick cutaneous melanoma with a Breslow > 1.5 mm (range 1.6-11 mm, n = 41, c-myc reactivity 29.6 +/- 23.8%, p = 0.46). No correlation of c-myc expression between thin cutaneous melanoma, thick cutaneous melanoma (p = 0.83) or metastasizing primaries and their metastases (n = 24, c-myc reactivity 29.3 +/- 22%) was found (p = 0.64). The time period until development of first metastasis did not correlate with the percentage of cells expressing c-myc in the primary (p = 0.56). CONCLUSION: c-myc expression is independent of metastatic potential and onset of metastases and, therefore, does not serve as a prognostic immunohistochemical marker in primary cutaneous melanoma.

Adult↗

PubMed1998

Adaptation of rat type II pneumocytes to NO2: effects of NO2 application mode on phosphatidylcholine metabolism.

Previous studies have shown that nitrogen dioxide (NO2) inhalation affects the extracellular surfactant as well as the structure and function of type II pneumocytes. Since in these studies there were great variabilities in oxidant concentration, duration of exposure, and mode of NO2 application, we evaluated the influence of the NO2 application mode on the phospholipid metabolism of type II pneumocytes. Rats were exposed to identical NO2 body doses (720 ppm x h), which were applied continuously (10 ppm for 3 d), intermittently (10 ppm for 8 h per day, for 9 d), and repeatedly (10 ppm for 3 d, 28 d rest, and then 10 ppm for 3 d). Immediately after exposure, type II cells were isolated and evaluated for cell yield, vitality, phosphatidylcholine (PC) synthesis, and secretion. Type II pneumocyte cell yield from animals that had been continuously exposed to NO2 was significantly increased, whereas intermittently and repeatedly treated rats exhibited cell yields that were nonsignificantly enhanced. Vitality of the isolated type II pneumocytes was not affected by the NO2 exposure modes. Continuous application of 720 ppm x h NO2 resulted in increased activity of the cytidine-5-diphosphate (CDP)-choline pathway. After continuous NO2 application, specific activity of choline kinase, cytidine triphosphate (CTP):cholinephosphate cytidylyltransferase, uptake of choline, and pool sizes of CDP-choline and PC were significantly increased over those of controls. Intermittent application of this NO2 body dose also provoked an increase in PC synthesis, but this increase was less prominent than after continuous exposure. After repeated exposure, the synthesis parameters were comparable to those for cells from control animals. Whereas PC synthesis in type II cells was obviously stimulated by NO2, the secretory activity of the cells was reduced. Continuous exposure reduced this activity most, whereas intermittent exposure nonsignificantly reduced this activity as compared with that of controls. The repeated application of NO2 produced no differences. We conclude that type II pneumocytes adapt to NO2 atmospheres depending on the mode of its application, at least for the metabolism of PC and its secretion from isolated type II pneumocytes. Further studies are necessary to determine whether additional metabolic activities will also adapt to NO2 atmospheres, and if these observations are specific for NO2 or represent effects generally due to oxidants.

Adaptation, Physiological↗

PubMed1998

Invasion of human cartilage by cultured multicellular spheroids of rheumatoid synovial cells--a novel in vitro model system for rheumatoid arthritis.

OBJECTIVE: A new 3-dimensional cell culture system was established to examine the invasion of rheumatoid synovial cells into cartilage. METHODS: Synovial cells from 20 patients with rheumatoid arthritis (RA) and 15 patients with osteoarthritis (OA) were co-cultured as multicellular spheroids with cartilage fragments. RESULTS: After 4 weeks the rheumatoid spheroids eroded the cartilage. The destruction of cartilage was supported by a high expression level of cathepsin D and matrix metalloproteinases. In contrast, the OA tissue showed attachment to the cartilage only. CONCLUSION: Our results indicate that spheroid/cartilage co-cultures seem to be a suitable in vitro model for the study of destructive cellular mechanisms that occur in RA.

Arthritis, Rheumatoid↗

PubMed1998

[Attenuation corrected myocardial PET after application of 18FDG: effect on the determination of regional myocardial uptake values].

AIM: Post injection transmission measurement (PIT) can be performed using rotating 68Ge/68Ga linesources. This study estimates attenuation coefficients, count densities and relative regional uptake values of PIT corrected cardiac PET (E-PIT) compared to routinely pre-injection transmission measurement (RT). METHODS: A thorax-phantom with homogeneously filled myocardium or with simulated defects and six patients with advanced coronary artery disease were studied using ECAT Exact tomograph (Siemens CTI) equipped with three rotating linesources. Transmission was performed twice (PIT, RT), attenuation coefficients and emission data were analysed, the latter without attenuation correction (E-UK), corrected with PIT (E-PIT) and with RT (E-RT) (count density, standard and relative uptake values). RESULTS: Both in phantom and patient studies attenuation coefficients differed significantly between PIT and RT. Comparing E-PIT and E-RT, regional uptake values were different only in phantom simulation with myocardial radioactivity concentrations higher than 10 kBq x ml-1. The image contrast between defects and remaining myocardium in the phantom studies or the standard and relative uptake values in patient studies did not vary significantly. CONCLUSION: Under clinical conditions a post injection transmission measurement does not influence the accuracy of regional myocardial uptake values relevantly.

Biological Transport↗

PubMed1997

The importance of the back-signal from T cells into antigen-presenting cells in determining susceptibility to parasites.

It has long been known that certain MHC class II genes can dominantly suppress immune responses and so increase susceptibility to parasite infections, but the mechanism has been unclear. Recent work has revealed one way in which this form of suppression may operate, through gating by MHC class II molecules of the back-signal from activated T cells into macrophages. The two known suppressive genes of the mouse are expressed in macrophages more extensively than are other class II genes. This is associated with suppression of IL-4 production resulting, we infer, from overproduction in the macrophages of IL-12, the counter-cytokine to IL-4. The lack of IL-4 may itself be immunosuppressive, even for Th2 responses, and excess IL-12 can overinduce the antiproliferative cytokine IFN-gamma. Although this mechanism requires further substantiation, we believe that it offers a reasonable answer to an old conundrum.

Animals↗

PubMed1997

Integrin alphaIIb beta3 reconstituted into lipid bilayers is nonclustered in its activated state but clusters after fibrinogen binding.

Integrin activation, ligand binding, and integrin clustering were analyzed using alphaIIb beta3 reconstituted into phospholipid vesicles and into supported planar lipid bilayers. Strong and specific binding of fibrinogen and the gamma-chain dodecapeptide of fibrinogen to alphaIIb beta3 indicated that the integrin is in an activated state after membrane reconstitution. Cryoelectron and fluorescence microscopy suggested a nonclustered state of the protein in the vesicle membrane. Supported planar lipid membranes were generated by fusion of vesicles in which approximately equal fractions of integrins were pointing inside-out and outside-in. This distribution led to an immobilization of about 40% of the integrin in supported bilayers due to attachment of the large extracellular domains to the quartz support. Fluorescence recovery after photobleaching indicated a diffusion coefficient of D = (0.70 +/- 0.06) x 10(-8) cm2/s, consistent with a nonclustered state of the mobile integrin. Upon fibrinogen binding, the integrins became immobile, and fluorescence micrographs showed a patchy distribution of fibrinogen-integrin complexes consisting of approximately 250 molecules. In addition to the expected dimer formation by bivalent fibrinogen, additionally induced fibrinogen clustering may account for the large size of the complexes. In contrast, binding of monovalent GRGDS pentapeptide or the gamma-chain dodecapeptide of fibrinogen altered neither the mobile fraction nor the association state of alphaIIb beta3. Our data indicate that integrin alphaIIbb3 is activated while monodisperse, and became clustered upon fibrinogen binding, leading to an irreversibly bound state.

Amino Acid Sequence↗

PubMed1997

Characterization of the calf thymus hairpin-binding factor involved in histone pre-mRNA 3' end processing.

Using ion exchange chromatography we have enriched the RNA hairpin-binding factor involved in histone pre-mRNA processing from calf thymus whole cell extract. We demonstrate that the interaction of the factor with its target RNA sequence, the hairpin structure located at the 3' end of mature histone mRNA, is sequence-specific and highly salt-resistant. We have developed a simple in vitro system which allows detection of activities stimulating histone pre-mRNA 3' end processing, based on mouse cell nuclear extract fractionated by Mono Q column chromatography. Using this system, we show that the bovine hairpin-binding factor participates in histone pre-mRNA 3' end processing in vitro. We have further purified the hairpin-binding factor in form of a RNA.protein complex by RNA-mediated elution from phosphocellulose. This led to a fraction highly enriched for 2 proteins of 40 and 43 kDa.

Animals↗

PubMed1997

The gene for histone RNA hairpin binding protein is located on human chromosome 4 and encodes a novel type of RNA binding protein.

The hairpin structure at the 3' end of animal histone mRNAs controls histone RNA 3' processing, nucleocytoplasmic transport, translation and stability of histone mRNA. Functionally overlapping, if not identical, proteins binding to the histone RNA hairpin have been identified in nuclear and polysomal extracts. Our own results indicated that these hairpin binding proteins (HBPs) bind their target RNA as monomers and that the resulting ribonucleoprotein complexes are extremely stable. These features prompted us to select for HBP-encoding human cDNAs by RNA-mediated three-hybrid selection in Saccharomyces cerevesiae. Whole cell extract from one selected clone contained a Gal4 fusion protein that interacted with histone hairpin RNA in a sequence- and structure-specific manner similar to a fraction enriched for bovine HBP, indicating that the cDNA encoded HBP. DNA sequence analysis revealed that the coding sequence did not contain any known RNA binding motifs. The HBP gene is composed of eight exons covering 19.5 kb on the short arm of chromosome 4. Translation of the HBP open reading frame in vitro produced a 43 kDa protein with RNA binding specificity identical to murine or bovine HBP. In addition, recombinant HBP expressed in S. cerevisiae was functional in histone pre-mRNA processing, confirming that we have indeed identified the human HBP gene.

Amino Acid Sequence↗

PubMed1997

The U7 snRNP and the hairpin binding protein: Key players in histone mRNA metabolism.

Animal replication-dependent histone mRNAs are subject to several post-transcriptional regulatory processes. Their non-polyadenylated 3' ends are formed preferentially during S phase by a unique nuclear cleavage event. This requires the base pairing between U7 snRNA and a histone spacer element 3' of the cleavage site. Cleavage occurs preferentially after adenosine, at a fixed distance from the hybrid region. A conserved RNA hairpin just upstream of the cleavage site is recognised by the hairpin binding protein (HBP) that acts as an auxiliary processing factor, stabilising the interaction of the histone pre-mRNA with the U7 snRNP. The interaction between HBP and the RNA hairpin is very stable and HBP is also found associated with histone mRNAs on polysomes. The hairpin and presumably, HBP are also required for nuclear export and translation of histone mRNA. Furthermore, histone mRNAs are selectively destabilised in the G2 phase or upon inhibition of DNA synthesis and this regulation is also associated with the hairpin. Recently, HBP-encoding cDNAs were isolated from various organisms. Human, mouse and Xenopus laevis HBPs are similar, while the Caenorhabditis elegans protein has significant homology to the others only in a central RNA binding domain.Copyright 1997 Academic Press Limited

Journal Article↗

PubMed1997

Comparative investigations of the neuronal apparatus in the pineal organ and retina of the rainbow trout: immunocytochemical demonstration of neurofilament 200-kDa and neuropeptide Y, and tracing with DiI.

The retina and pineal organ of the rainbow trout have been investigated immunocytochemically with antibodies against neurofilament 200-kDa (NF-200) and neuropeptide Y (NPY), which are known to label horizontal and amacrine cells in the retina of several vertebrates. The NF-200 immunoreaction stains horizontal cells of the retina, but not neuronal perikarya in the pineal organ. Axons of both the optic and the pineal tract display immunoreaction for NF. The NPY immunoreaction labels a population of amacrine cells in the retina, but is not detected in neuronal perikarya of the pineal organ. Single NPY-immunoreactive nerve fibers have been located in the capsule of the pineal organ. The data suggest that neurons corresponding to NF-200-immunoreactive horizontal and NPY-immunoreactive amacrine cells of the retina are missing from the pineal organ of the trout. Thus, the neuronal apparatus in the light-sensitive pineal organ appears to be less complex than that in the retina. This has been confirmed by tracing experiments with DiI: intrapineal neurons retrogradely labeled via the pineal tract are found in a postsynaptic location to processes of photoreceptor cells containing synaptic ribbons. These results indicate a bineuronal chain in the pineal organ of the rainbow trout comprising the photoreceptor cell as the first neuron and the ganglion cells forming the pineal tract as the second neuron. The NPY-immunoreactive nerve fibers in the capsule of the pineal organ may represent an autonomic innervation.

Animals↗

PubMed1997

The development of conditioned blocking and monoamine metabolism in children with attention-deficit-hyperactivity disorder or complex tics and healthy controls: an exploratory analysis.

Conditioned blocking (CB) measures the transient suppression of learning that a new stimulus, added during learning, has the same consequences as the conditioned stimulus already present. Normal CB increases between the age of 8 and 20 years (Oades, R.D., Roepcke, B. and Schepker, R., A. test of conditioned blocking and its development in childhood and adolescence: relationship to personality and monoamine metabolism, Dev. Neuropsychol., 12 (1996) 207-230). In the present study CB development is compared between healthy children (CN), children with attention deficit (ADHD) and those with complex tics or Tourette's syndrome (TS) with mean ages of 10-11 years. All children needed fewer learning trials with increasing age: the ADHD group showed a slight impairment. Only controls improved CB with increasing age. A trend for worse CB in the TS than the other groups was significant for those over 11 years. While ADHD children over 11 years showed less CB than controls, younger ADHD children showed more. A correlational analysis of the status of monoamine metabolism in 24 h urine samples showed a positive relationship for CB with dopamine metabolism in controls and TS children, but a negative relationship in ADHD children. In contrast, increases of serotonin metabolism were negatively related to CB in TS but positively in ADHD patients. In conclusion, when selective information processing abilities reflected by CB start to develop at puberty-onset, there is a relative worsening in ADHD patients. But TS patients show an impairment independent of age. Changes in the balance between dopamine and serotonin systems may contribute to normal and abnormal cognitive development.

Adolescent↗

PubMed1997

Evaluation of automatically learned intelligent alarm systems.

In this contribution it is investigated whether a combination of mathematical simulation and inductive machine learning can replace the usual knowledge elicitation techniques. To test this a domain was selected for which knowledge based systems had a high performance: intelligent alarm systems. A mathematical model of a breathing circuit and ventilated patient was implemented in PSpice. Airway pressure, gas flows and CO2 concentration were simulated with this model, during normal functioning of the breathing circuit and during several mishaps, for a wide range of simulated patients. With an inductive machine learning program, classification trees were created from the simulated patient data. The classification trees described each breathing circuit mishap in terms of changes in signal feature values with respect to the normal situation and were implemented as alarm system knowledge bases. The alarm systems were tested with data measured at 17 mechanically ventilated animals. During ventilation of the animals several mishaps were introduced. For each animal, 93-100% of all mishaps could be detected correctly by the alarm systems. The false alarm rate ranged on average from one false alarm per h to one false alarm every 2.5 h. It was concluded that the suggested approach to knowledge elicitation was successful.

Animals↗

PubMed1997

Functional expression of rat synapse-associated proteins SAP97 and SAP102 in Drosophila dlg-1 mutants: effects on tumor suppression and synaptic bouton structure.

The synapse-associated proteins SAP97 and SAP102 are mammalian proteins that are structurally related to the Drosophila tumor suppressor protein DlgA. Previous analyses revealed that DlgA is essential for the integrity of epithelia and neuromuscular synapses. Here we show that synaptic bouton structure is severely affected in mutant larvae carrying the dlg-1(XI-2) allele. We have tested SAP97 and SAP102 for functional homology to DlgA by heterologous expression in Drosophila. Both SAP97 and SAP102 can suppress tumor formation in dlg-1 mutant flies and mimic DlgA at larval neuromuscular junctions. Neuronal expression of SAP97 or SAP102 is required for morphological restoration of synaptic boutons, indicating that presynaptic DlgA function is essential for establishing structurally intact motor nerve terminals at larval neuromuscular junctions.

Adaptor Proteins, Signal Transducing↗

PubMed1997

[CT volumetry of the liver before transplantation].

PURPOSE: Purpose of the study was to assess the predictive accuracy of preoperative CT volumetry for water displacement volume after liver transplantation. METHODS: In a retrospective study the liver volume of 52 patients who underwent an orthotopic liver transplantation, was calculated preoperatively based on incremental and spiral computed tomography (CT). The calculated values were compared with the liver volume measured by water displacement and weight of the extirpated liver. RESULTS: Marked differences of 19-21.5% were seen between calculated CT volume and water displacement volume for the entire group, and of 12.4-16.9% for livers with a plausible physical liver density (0.9 and 1.1 g/cm3). In this group, 68-86% of the livers were in the acceptable tolerance range for a predictive accuracy (+10% to -20%). Other error sources, such as the breathing shift of the abdominal organs and interobserver variability (1.5-2.7%), were of minor importance for volume calculation. CONCLUSION: In conclusion, both incremental CT and spiral CT are reliable methods for the preoperative estimation of the liver volume, whereas best accordance with the corrected water displacement volume was obtained using the individual segmentation thresholds.

Adolescent↗

PubMed1997

Estimation of tissue hypothyroidism by a new clinical score: evaluation of patients with various grades of hypothyroidism and controls.

The classical signs and symptoms of hypothyroidism were reevaluated in the light of the modern laboratory tests for thyroid function. We analyzed 332 female subjects: 50 overt hypothyroid patients, 93 with subclinical hypothyroidism (SCH), 67 hypothyroid patients treated with T4, and 189 euthyroid subjects. The clinical score was defined as the sum of the 2 best discriminating signs and symptoms. Beside TSH and thyroid hormones, we measured parameters known to reflect tissue manifestations of hypothyroidism, such as ankle reflex relaxation time and total cholesterol. Classical signs of hypothyroidism were present only in patients with severe overt hypothyroidism with low T3, but were rare or absent in patients with normal T3 but low free T4 or in patients with SCH (normal thyroid hormones but elevated basal TSH; mean scores, 7.8 +/- 2.7 vs. 4.4 +/- 2.2 vs. 3.4 +/- 2.0; P < 0.001). Assessment of euthyroid subjects and T4-treated patients revealed very similar results (mean score, 1.6 +/- 1.6 vs. 2.1 +/- 1.5). In overt hypothyroid patients, the new score showed an excellent correlation with ankle reflex relaxation time and total cholesterol (r = 0.76 and r = 0.60; P < 0.0001), but no correlation with TSH (r = 0.01). The correlation with free T4 was r = -0.52 (P < 0.0004), and that with T3 was r = -0.56 (P < 0.0001). In SCH, the best correlation was found between the new score and free T4 (r = -0.41; P < 0.0001) and TSH (r = 0.35; P < 0.0005). Evaluation of symptoms and signs of hypothyroidism with the new score in addition to thyroid function testing is very useful for the individual assessment of thyroid failure and the monitoring of treatment.

Adult↗

PubMed1997

Frequent and frequently overlooked: treatment-induced endocrine dysfunction in adult long-term survivors of primary brain tumors.

New treatments for primary brain tumors have improved survival but quality of life may be impaired by neuroendocrine dysfunction. We performed a controlled, cross-sectional study to assess frequency and clinical impact of endocrine dysfunction in adult long-term survivors of primary brain tumors outside the hypothalamic-pituitary region. Thirty-one patients (19 males and 12 females; age, 25 to 66 years) and 31 sex- and age-matched controls were studied 1.5 to 11 years after radiotherapy with a mean total dose of 62.3 +/- 2.8 Gy (mean local doses pituitary, 51.1 +/- 12.1 Gy; hypothalamus, 57.0 +/- 7.8 Gy). Structured clinical assessment included a standardized questionnaire. Thyroid, adrenal, and gonadal hormones were measured at baseline and, in the patients, also after stimulation. Sixteen patients (52%) reported two or more symptoms suggestive of hypothyroidism; eight patients (26%) showed evidence of hypothalamic hypothyroidism. Patients had significantly lower serum baseline concentrations of cortisol and dehydroepiandrosterone sulfate than controls, but no manifest hypoadrenalism was noticed except in one patient with panhypopituitarism. Forty-seven percent of the male patients, but only six percent of the controls, suffered from erectile dysfunction; 42% of the male patients showed either evidence of hypothalamic hypogonadism (32%) or primary gonadal damage (10%). Nine patients (29%) presented with hyperprolactinemia and four women concurrently suffered from oligo-amenorrhea. In adult patients treated for primary brain tumors, endocrine dysfunction due to radiation-induced hypothalamic damage is common and has a significant impact on well being. Endocrinologic evaluation should be performed periodically in these patients.

Adrenal Glands↗

PubMed1997

[A method for combined scatter and attenuation correction without transmission measurement for myocardial SPECT with 99m-Tc binding].

AIM: A new strategy is introduced for a double-head gamma-camera to calculate and to correct for attenuation distribution from count rates of backscattered radiation of 99mTc in the human thorax/myocardium setting. The intention was to gain segmented and calibrated images of distribution employing the structures of lungs and other tissues, so that attenuation may be subsequently corrected by the method of Chang METHODS: Acquisition was done simultaneously in three energy window for 99mTc to receive both emitted and scattered radiation. The acquire projections were used to calculate the attenuation distribution and to execute a scatter correction by the method of Ogawa et. al. By measuring phantoms and evaluating a set of patient studies, quality for both of the approaches towards attenuated distribution and the quality of attenuation correction was tested and an optimal setting for parameters involved was selected. RESULTS: The procedure adequately approaches the correction for both emitted and scattered radiation in SPECT, as experienced in phantom and patient studies. Clinical usefulness was preliminary documented in selected cases. In normal perfusion, distribution was more homogeneous. Perfusion defects appeared more definitive. Problems occurred in high adjacent non-target activity (e.g., in the gallbladder) and with low count rate statistics. CONCLUSION: Myocardial 99mTc MIBI SPECT may be effectively corrected for both attenuation a scatter without an additional transmission device.

Heart↗

PubMed1997

Microvascular pathology in the skeletal muscle paraneoplastic phenomenon.

An electron microscopic investigation was made in order to study capillary alterations in the muscle paraneoplastic phenomenon associated with different malignant tumours. Several abnormalities were found including basement membrane widening and lamination, endothelial hypertrophy, a varied degree of lumen occlusion, and proliferative changes in pericytes. A degenerative process leading to capillary necrosis was also observed. A mononuclear cell infiltrate formed by macrophages, lymphocytes and mast cells was seen. The capillary changes observed suggest the existence of an autoimmune vascular factor in the etiopathogenesis of muscle damage in this phenomenon.

Capillaries↗