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Biomedical subjects

K Müller

Publications and source records attributed to K Müller.

At least 91 records · Page 5Linked to original sources

[Morphology of neurological complications of intravascular lymphomatosis].

Intravascular lymphomatosis (IVL) is a rare lymphoproliferative disease characterized by intravascular growth of lymphoma cells in small vessels. Most frequently, its first manifestations occur in the central nervous system or skin. Based on autoptical findings in a 68-year-old-man with IVL, the pathological morphology in the central nervous system is compared to the course of neurological symptoms. The disease could not be diagnosed during his lifetime. The spectrum of neurological deficits can be explained histopathologically by occlusive intravascular aggregations of lymphomatous cells in small vessels of the spinal leptomeninges and nerve roots causing perfusion deficits and areas of ischemic necrosis of up to 4 mm in diameter in the medulla. Aggregations of lymphoma cells in the vessels of other organs are also found, but did not result in clinical symptoms. In reference to the present case, a survey of other literature reports on IVL with neurological and psychiatric manifestations is given. In patients with this condition, even an invasive biopsy has to be considered in order to make the correct diagnosis at an early clinical stage.

Aged↗

Depsides as non-redox inhibitors of leukotriene B(4) biosynthesis and HaCaT cell growth, 2. Novel analogues of obtusatic acid.

Aseries of obtusatic acid analogues has been synthesized and evaluated as inhibitors of leukotriene B(4) (LTB(4)) biosynthesis and as antiproliferative agents. The 4-O-benzylated and the 4-O-demethylated congeners were the most potent inhibitors of LTB(4) production of the depside class of compounds, with IC(50) values in the submicromolar range. Furthermore, these compounds do not function as redox-based inhibitors because they were not reactive against a stable free radical, 2,2-diphenyl-1-picrylhydrazyl, and did not produce appreciable amounts of deoxyribose degradation as a measure of their potency to generate hydroxyl radicals. Some obtusatic acid congeners were also potent inhibitors of keratinocyte growth. Growth inhibition was not mediated by damage to the cell membrane, as the activity of lactate dehydrogenase released from the cytoplasm was in the control range.

Animals↗

Medicinal plants from nepal: evaluation as inhibitors of leukotriene biosynthesis.

The methanolic extracts of 25 different Nepalese medicinal plants were tested for their activity to inhibit the biosynthesis of leukotriene B(4) in bovine polymorphonuclear leukocytes. The selected indigenous plants are used in traditional herb remedies to treat inflammatory diseases such as asthma, bronchitis, rheumatism, and skin disorders presumed to be mediated by leukotrienes. The leaves of Zanthoxylum nepalensis were shown to be the most potent inhibitor with an IC(50) value of 11 microgram/ml. The extracts obtained from Astercantha longifolia and Hedychium ellipticum also exhibited potent inhibitory action with IC(50) values of 20 and 22 microgram/ml, respectively.

Humans↗

Antioxidative capacity in patients with common variable immunodeficiency.

Highly reactive oxygen species (ROS) are involved in T-cell activation and in the defense against environmental pathogens. An imbalance of ROS generation, detoxifying scavenger enzymes, and molecules with antioxidant capacity could contribute to the increased susceptibility to cancer and infections in severe humoral immunodeficiency. We studied antioxidant status, i.e., plasma antioxidant capacity (TEAC), retinol, alpha-to-copherol, ubiquinol, and the number of activated T cells in 16 patients with common variable immunodeficiency (CVID) compared to age-matched healthy controls. As expected, patients showed significantly increased levels of activated HLA-DR and CD45RO-expressing T cells. Plasma levels of the endogenous ROS scavenger ubiquinol (Q 10) were significantly lower in patients as compared to controls. However, patients showed only slightly reduced levels of TEAC as well as the exogenous antioxidants retinol and alpha-tocopherol. Although no correlation of the number of activated T cells and antioxidant capacity could be demonstrated, an increase in ROS and a diminished reactive oxygen scavenger capacity may be involved in the disease process in patients with common variable immunodeficiency.

Adolescent↗

[Rehabilitation and the Internet].

An overview is presented of the technical conditions, approaches, existing Internet services, famous homepages about rehabilitation in the Internet (WWW) as well as other possibilities of obtaining information via the Internet.

Directories as Topic↗

Expression of PGF(2alpha) receptor mRNA in normal, hyperplastic and neoplastic skin.

Reverse transcription polymerase chain reaction (RT-PCR) and Northern blot analysis was used to determine the level of expression of prostaglandin F(2alpha) (FP) receptor mRNA in various mouse tissues, including normal, hyperplastic and neoplastic mouse epidermis. Steady-state concentrations of FP receptor mRNA were low in normal and hyperplastic epidermis. The response of the epidermis to the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was biphasic in that FP receptor mRNA was increased immediately after treatment, followed by a long-lasting down-regulation at later time points. FP receptor mRNA was down-regulated in the majority of papillomas obtained by the mouse skin carcinogenesis initiation-promotion protocol. In carcinomas, FP receptor mRNA expression was similar to that in normal epidermis. The steady-state concentration of FP mRNA was inversely correlated with PGF(2alpha) levels in normal and hyperplastic epidermis and in papillomas, indicating that FP mRNA expression is regulated by this eicosanoid.

Adolescent↗

On the origin and domestication history of Barley (Hordeum vulgare).

Remains of barley (Hordeum vulgare) grains found at archaeological sites in the Fertile Crescent indicate that about 10,000 years ago the crop was domesticated there from its wild relative Hordeum spontaneum. The domestication history of barley is revisited based on the assumptions that DNA markers effectively measure genetic distances and that wild populations are genetically different and they have not undergone significant change since domestication. The monophyletic nature of barley domestication is demonstrated based on allelic frequencies at 400 AFLP polymorphic loci studied in 317 wild and 57 cultivated lines. The wild populations from Israel-Jordan are molecularly more similar than are any others to the cultivated gene pool. The results provided support for the hypothesis that the Israel-Jordan area is the region in which barley was brought into culture. Moreover, the diagnostic allele I of the homeobox gene BKn-3, rarely but almost exclusively found in Israel H. spontaneum, is pervasive in western landraces and modern cultivated varieties. In landraces from the Himalayas and India, the BKn-3 allele IIIa prevails, indicating that an allelic substitution has taken place during the migration of barley from the Near East to South Asia. Thus, the Himalayas can be considered a region of domesticated barley diversification.

Base Sequence↗

Does P3 reflect attentional or memory performances, or cognition more generally?

The study evaluated the off-line relationship of attention, memory and other cognitive performances with the auditory event-related potentials P3 (P300) and N2. The sample comprised 200 middle-aged construction workers. Verbal, visuomotor and memory tests were administered. Attentional domains were examined using CogniSpeed software. Slowed reaction times in the test of sustained attention (vigilance) were associated with delayed P3 latency (p < 0.001) and decreased P3 amplitude (p = 0.005), as well as with delayed N2 latency (p < 0.001). Visuomotor slowing in Digit Symbol was also related to delayed P3 latency (p = 0.030) and decreased P3 amplitude (p = 0.014). In contrast, mild cognitive impairment, short- and long-term memory, and concentrating or sharing attention with high working memory demands were not related to P3. The results suggest that P3 is linked to attentional performance with low working memory demands rather than to effortful working memory updating, retrieval from memory stores, or mild cognitive impairment.

Adult↗

Expression analysis of ataxin-7 mRNA and protein in human brain: evidence for a widespread distribution and focal protein accumulation.

Spinocerebellar ataxia 7 (SCA7) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG-trinucleotide repeat in the coding region of the SCA7 gene. The expansion is translated into an extended polyglutamine stretch in the protein ataxin-7, a protein of unknown function. By Northern blot analysis expression of ataxin-7 was detected in numerous regions of human brain and some peripheral tissues. It is unknown, however, if ataxin-7 is enriched at sites of the SCA7 pathology. We studied the regional and cellular expression pattern of ataxin-7 at the mRNA level by in situ hybridization histochemistry in normal human brain. Furthermore we used a monoclonal and two polyclonal antibodies raised against the normal ataxin-7 to establish the distribution of this protein in brain, retina and peripheral organs. At the mRNA level ataxin-7 was preferentially expressed in neurons; the regional distribution reflected neuronal packing density. Ataxin-7 immunoreactivity (IR) was similarly widely expressed. In most neurons, ataxin-7 IR was preferentially localized to the cytoplasmatic compartment although some nuclear ataxin-7 IR was detected in most neurons. A more intense and more prominently nuclear ataxin-7 IR was observed in neurons of the pons and the inferior olive, brain regions severly affected by the disease, suggesting that the subcellular localization and abundance of ataxin-7 is regulated in a regionally specific way. Since neurons displaying more intense and more prominently nuclear ataxin-7 IR belonged to the class of susceptible cells in SCA7, an enrichment of normal ataxin-7 in the nuclear compartment may contribute to neurodegeneration. However not all sites of SCA7 pathology displayed a strong cytoplasmatic and nuclear immunoreactivity.

Ataxin-7↗

Co-expression of vascular endothelial growth factor and its receptor flt-1 in malignant pleural mesothelioma.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic protein with a selective mitogenic effect on endothelial cells known to be involved in many normal and pathological processes. Coexpression of VEGF and its receptor flt-1 has been reported in different types of malignant tumors. OBJECTIVE: In the present study we investigated the expression of VEGF and flt-1 in 90 cases of diffuse malignant pleural mesotheliomas. METHODS: VEGF and flt-1 expression was analyzed by immunohistochemistry and non-radioactive in situ hybridization. RESULTS: VEGF expression was visualized immunohistochemically in tumor cells. flt-1 expression correlated with histological differentiation (p < 0.013). Furthermore, expression of flt-1 was detected in tumor cells, macrophages and microvessels adjacent to tumor cells. VEGF and flt-1 expression were confirmed by in situ hybridization. CONCLUSION: There was a statistically significant correlation between VEGF and flt-1 expression (p < 0.001). The observed coexpression of VEGF and flt-1 possibly suggests a potential autocrine loop for malignant pleural mesothelioma cells.

Aged↗

Neuromagnetic correlates of sensorimotor synchronization.

Sensorimotor synchronization tasks, in which subjects have to tap their finger in synchrony with an isochronous auditory click, typically reveal a synchronization error with the tap preceding the click by about 20 to 50 msec. Although extensive behavioral studies and a number of different explanatory accounts have located the cause of this so-called "negative asynchrony" on different levels of processing, the underlying mechanisms are still not completely understood. Almost nothing is known about the central processes, in particular, which sensory or motor events are synchronized by subjects. The present study examined central-level processing in synchronization tasks with magnetoencephalography (MEG). Eight subjects synchronized taps with their right index finger to an isochronous binaural pacing signal presented at an interstimulus interval of 800 msec. To gain information on central temporal coupling between "tap" and "click," evoked responses were averaged time-locked to the auditory signal and the tap onset. Tap-related responses could be explained with a three dipole model: One source, peaking at approximately 77 msec before tap onset, was localized in contralateral primary motor cortex (MI); the two other sources, peaking approximately at tap onset and 75 msec after tap onset, in contralateral primary somatosensory cortex (SI). Temporal coupling of these sources was compared in relation to different trigger points. The second SI source was equally well time-locked to the tap and to the auditory click. Furthermore, analysis of the time locking of this source activity as a function of the temporal order of tap and click showed that the second event - irrespective whether tap or click - was decisive in triggering the second SI source. This suggests that subjects use mainly sensory feedback in judging and evaluating whether they are "keeping time."

Acoustic Stimulation↗

Current status and recent developments in anthracenone antipsoriatics.

Treatment of psoriasis is rapidly changing, and there have been dramatic additions such as topical vitamin D analogs and a topical retinoid to the therapeutic armamentarium in recent years. Even though drug therapy is often inadequate and serves only to abate the skin disorder, anthralin of the anthracenone antipsoriatics clears the rash totally. Of all antipsoriatic agents, anthralin has proven to be the most remarkably consistent and time-honored drug for treating the disease. However, anthralin therapy is accompanied by inflammation and staining of the nonaffected skin surrounding a psoriatic lesion. A large body of evidence has shown that the biochemical basis for its mechanism of action at the molecular level is related to its redox chemistry leading to the production of oxygen radicals. These can react with all classes of biological macromolecules and are involved in the principal cellular effects of the anthracenones. This article will focus on current strategies to minimize the potential of skin inflammation by anthralin and the underlying concepts of controlling and manipulating oxygen-radical generation which are essential for the rational design of novel anthracenones. Various studies have shown that by altering the structure of anthralin the in vitro profile can be markedly altered from an only moderate 5-lipoxygenase inhibitor to a more potent inhibitor of this enzyme, which may reflect improved activity against the inflammatory component of psoriasis while the antiproliferative activity is retained. The structural change is also accompanied by significantly diminished oxygen-radical generation and proinflammatory action on the skin. In particular, derivatives bearing a phenylacyl substituent in the critical 10-position of the anthracenone molecule have a favorable overall profile for achieving improved topical therapy of psoriasis.

Anthracenes↗

Molecular analysis of homeotic genes involved in barley development.

Ectopic expression of the barley homeobox gene BKn-3 conditions the development of epiphyllous flowers by de novo meristem formation. Various strategies are being described in an effort to identify genes whose products interact with the BKn-3 gene product or BKn-3 regulatory regions.

Chromosome Mapping↗

[Autopsy in peri- and neonatology--an essential step in quality control. Data on autopsy frequency in Saxony].

In the framework of a general quality assurance compaign the working group for peri- and neonatology at the General Medical Council of Saxony has investigated the frequency, conclusiveness and development of autopsies in Saxony between 1992 and 1997/98. There were observable different autopsy rates depending on the degree of neonate maturity. Thus, the autopsy rate of stillbirths having birth weights from 500 to 999 g amounted to 79.7%, and that of stillbirths above 1000 g birth weight to only 59.4%. The abduction rate of neonates dying before day 7 of life was 65.7%. It is remarkable that the abduction rates declines from 79.1 to 62.9% in all weight classes of premature and full-term neonates from 1992 to 1997. The possible reasons for the decline of autopsies and the problems emerging for quality assurance are discussed.

Autopsy↗

Undergraduate medical education: tendencies and requirements in a rapidly developing Europe.

This study pinpoints the necessity to constantly monitor local approaches in undergraduate medical education on an inter-European scale. Traditional undergraduate medical curricula need restructuring to account for the increasing amount of medical knowledge and rapid changes and developments in societies, nosology, therapy and IT. European undergraduate medical curricula should be harmonized not egalized, with a focus on inter-European sharing of resources, mobility, credit (allocation, accumulation and transfer), definition of European and trans-European mission statements, identification of quality metrics, advice on dealing with conflicting aims such as specialization and generalization, on communicating core knowledge instead of providing overabundance of information, and on introducing multifaceted teaching and learning methods, as well as providing strategies for life long learning. Sound medical education can no longer and nowhere be considered under the autonomous auspices of individual Medical Schools or national philosophies. It has to be perceived and structured as a competitive and flexible approach which promotes life long learning of teachers, students, physicians and other related staff with international awareness. It is stressed that student and staff mobility, as well as virtual mobility in the form of worldwide available teaching modules and expertise have to be incorporated into national medical curricula. This is to guarantee up-to-date education in support of patient demands, future professionality and competitiveness of students, physicians and Public Health System institutions. The formal approaches of traditional subject related curricula as well as problem based learning must be linked with quality approved state of the art ODL, evaluated international CME strategies and training in the utilization of IT in preparation of lifelong learning. Strategies for the use of IT need updating on a regular basis to diminish the gap between undergraduate and postgraduate medical education. General European perspectives of medical education are discussed in relation to ECTS, ODL, compulsory credited and evaluated CME and relicensing of physicians. Prime features of ETM--the most reputed and well-known European medical CME initiative fostering quality assured international awareness are described and recommended for local and nationwide implementation. Specific links of the Bonn undergraduate medical curriculum with credited and evaluated CME and imminent European strategies are detailed. The authors conclude that European universities not adapting at least some of the outlined curricular necessities will rapidly lose their competitiveness compared to other national and international Medical Schools. Harmonized European ethical mission statements and consequent utilization of IT deserve special considerations in this context.

Computer-Assisted Instruction↗

Solid-state NMR and FTIR studies on bilayer membranes from 1,2- dioctadec-(14-ynoyl)-sn-glycero-3-phosphatidylcholine.

Multilamellar dispersions from a new model phospholipid, 1, 2-dioctadec-(14-ynoyl)-sn-glycero-3-phosphatidylcholine (DO(14-yne)PC), bearing a triple bond in the fatty acid chains are studied by (2)H, (31)P NMR and Fourier transform infrared (FTIR) spectroscopy. The investigations are focused on the evaluation of the molecular properties of the lipid molecules as function of temperature and sample composition. Information about the fatty acid chain conformations are obtained from FTIR measurements by analysing the CH(2) wagging and stretching modes. (2)H NMR studies are performed on two selectively deuterated compounds that provide further insights into the molecular characteristics at two specific positions along the fatty acid chains. These studies demonstrate that the introduction of the triple bond is accompanied by a reduction of fatty acid chain order which holds for both the conformational and the orientational order. Likewise, (31)P NMR spectroscopy is used for the determination of the dynamics and ordering in the head group region. Here, particular emphasis is given to the evaluation of the lipid lateral motions that are quantified over a large temperature range within the liquid crystalline phase. It is found that the lateral mobility of the lipid molecules is almost unaffected by the triple bond in the fatty acid chains. The addition of cholesterol gives rise to a reduction in lateral mobility for DO(14-yne)PC, as can be followed by spin echo, 2D-exchange NMR and stimulated echo experiments.

Crystallization↗