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Biomedical subjects

M Bender

Publications and source records attributed to M Bender.

At least 19 recordsLinked to original sources
PubMed2006

[Serologic early diagnosis of pneumonia caused by Mycoplasma pneumoniae].

BACKGROUND AND OBJECTIVE: The definitive diagnosis of M. pneumoniae is encumbered by the lack of a rapid and cost-effective test of detection. The study aimed to determine if a single serological test within the first days of hospital admission may be relevant for the diagnosis of community-acquired pneumonia (CAP) caused by M. pneumoniae. PATIENTS AND METHODS: Patients with suspected of CAP were investigated for microbiological diagnosis based on respiratory samples (bronchoalveolar lavage, bronchial aspirate, sputum, throat rinse), blood culture and serology for detection of atypical organisms and viruses. Patients with M. pneumoniae antibody titers > or = 1:160 were further investigated by polymerase chain reaction (PCR) for detection of M. pneumoniae in respiratory samples. The group of CAP by M. pneumoniae (MP-CAP) included patients with serum titers > 1:160 of M. pneumoniae antibodies (based on a single antibody determination at admission). The control group (non-MP-CAP group) included patients with CAP by pathogens other than M. pneumoniae or with no definitive bacteriological diagnostic. RESULTS: Twenty adults with MP-CAP and 20 controls with non-MP-CAP were included. PCR was positive in 18/20 (90 %) of the MP-CAP group and negative in the 9/9 (100 %) investigated patients of the non-MP-CAP group. The duration of symptoms prior to hospital admission was rather long in both groups (mean 13.2 days in the MP-CAP group and 12,7 days in the non-MP-CAP group). The MP-CAP group was significantly younger (p = 0.002), had subsequently less associated comorbidities (p < 0.001) and less purulent sputum (p = 0.003) than the non-MP-CAP group. CONCLUSION: Single serology at admission with M. pneumoniae antibody titers > 1:160 may be useful for the diagnosis of CAP caused by M. pneumoniae in hospitalized patients with a long duration of symptoms (> 12 days).

Adult↗
PubMed2005

Systematics of quadrupolar correlation energies.

We calculate correlation energies associated with the quadrupole shape degrees of freedom with a view to improving the self-consistent mean-field theory of nuclear binding energies. Systematic results are presented for 605 even-even nuclei from mass number 16 to the heaviest whose mass has been measured, using the Skyrme SLy4 interaction and the generator coordinate method. Correlation energies range from 0.5 to 6.0 MeV, and their inclusion improves two qualitative deficiencies of the mean-field theory, namely, the exaggerated shell effect at neutron magic numbers and the failure of mean-field theory to describe mutually enhanced magicity. For the mass table as a whole, the quadrupolar correlations improve binding energies, separation energies, and separation energy differences by 20%30%.

Journal Article↗
PubMed2004

Creation of EcR isoform-specific mutations in Drosophila melanogaster via local P element transposition, imprecise P element excision, and male recombination.

Collections of single P transposable-element insertion strains that currently inactivate more than 25% of essential Drosophila genes have proven to be a valuable tool for genome research in Drosophila melanogaster. For genes unrepresented in these collections, strategies including local P element transposition and transposase-induced imprecise excision can be used to inactivate or delete the gene of interest. Here we report our use of local P element transposition followed by imprecise P element excision and transposase-induced male recombination to generate two deficiencies specific for the EcR-A isoform of the ecdysone receptor ( EcR) gene, and four larger deficiencies likely to affect multiple EcR functions. We also report here the determination of sequences flanking six EcR-B deficiencies generated in a previous imprecise excision screen. EcR-A encodes one of a family of three related nuclear receptor proteins that, together with the heterodimer partner USP, mediate ecdysone signaling during Drosophila development. Our results delineate sequences required in vivo for EcR-A function, as well as identifying EcR-A intron 1 sequences that are not essential for EcR function.

Animals↗
PubMed2003

[Causes for in-hospital treatment of nursing home residents].

The high rates of hospitalization in nursing home residents are as well known as the hazards of in-hospital treatment especially in this group of frail older people. Moreover, hospital admissions cause considerable costs. The objective of the study was to analyze why nursing home residents are admitted for in-hospital geriatric care, and to form hypotheses of how to prevent these admissions without loss of quality of care. Reason of admission, comorbidity, competence and length of in-hospital stay were assessed in all nursing home residents referred to the Geriatric Centre at the University Hospital of Heidelberg over 12 months. There were 245 admissions of 231 nursing home residents (83.1% female; age 84.2 +/- 7.10 years). Comorbidity was substantial (77% urinary incontinence, 69% dementia, 40% stool incontinence, 22% pressure ulcers), and 56% of residents needed assistance in using the toilet before admission. Mean length of in-hospital stay was 32.6 days (median 29 days). Out of a total amount of 7983 days of in-hospital care, 3627 (45%) were caused by falls and fractures, 2039 (26%) by cardiovascular events (mainly ischemic stroke), 835 (11%) by infections and 495 (6%) by problems concerning nutrition. Most of the leading causes of admission of nursing home residents to in-hospital geriatric care might be affected by improvements in nursing home care. Thus, data suggest that hospitalization rates might be substantially reduced by targeted prevention and therapy as well as by structural measures to improve case management in the nursing homes. Such interventions should be developed and proved in controlled studies.

Activities of Daily Living↗
PubMed2002

Incorporating long-term trends in water availability in water supply planning.

This paper examines factors affecting water availability and hydrological trends of water supply. The relative impacts of the different factors have been assessed on a planning time frame of around 30 years. It is demonstrated that the non-greenhouse processes of multi-decadal climate change and el Niño-la Niña climate change will almost certainly be more significant than greenhouse induced climate change. Further, in developing countries, increased water consumption, population growth, and urbanization are likely to be the dominant factors when considering water availability. The type of responses that a water supply organization can make are discussed.

Conservation of Natural Resources↗
PubMed2001

Broad-complex, but not ecdysone receptor, is required for progression of the morphogenetic furrow in the Drosophila eye.

The progression of the morphogenetic furrow in the developing Drosophila eye is an early metamorphic, ecdysteroid-dependent event. Although Ecdysone receptor-encoded nuclear receptor isoforms are the only known ecdysteroid receptors, we show that the Ecdysone receptor gene is not required for furrow function. DHR78, which encodes another candidate ecdysteroid receptor, is also not required. In contrast, zinc finger-containing isoforms encoded by the early ecdysone response gene Broad-complex regulate furrow progression and photoreceptor specification. br-encoded Broad-complex subfunctions are required for furrow progression and proper R8 specification, and are antagonized by other subfunctions of Broad-complex. There is a switch from Broad complex Z2 to Z1 zinc-finger isoform expression at the furrow which requires Z2 expression and responds to Hedgehog signals. These results suggest that a novel hormone transduction hierarchy involving an uncharacterized receptor operates in the eye disc.

Animals↗
PubMed2000

Anisotropic diffusion in a nematic liquid crystal- An electric field PFG NMR approach

The access to self-diffusion coefficients in anisotropic systems such as thermotropic liquid crystals by means of PFG NMR is complicated by strong dipolar interactions. Additionally, problems arise due to the immediate orientation of low-molar-mass nematic liquid crystals in an external field. The director orientation can be changed by the application of an additional electric field. This can be exploited in order to reduce the dipolar interaction to such an extent that the NMR linewidths change from a solid-state to a liquid-like situation enabling PFG NMR experiments. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

The Drosophila ecdysone receptor (EcR) gene is required maternally for normal oogenesis.

Oogenesis in Drosophila is regulated by the steroid hormone ecdysone and the sesquiterpenoid juvenile hormone. Response to ecdysone is mediated by a heteromeric receptor composed of the EcR and USP proteins. We have identified a temperature-sensitive EcR mutation, EcR(A483T), from a previously isolated collection of EcR mutations. EcR(A483T) is predicted to affect all EcR protein products (EcR-A, EcR-B1, and EcR-B2) since it maps to a common exon encoding the ligand-binding domain. In wild-type females, we find that both EcR-A and EcR-B1 are expressed in nurse cells and follicle cells throughout oogenesis. EcR mutant females raised at permissive temperature and then shifted to restrictive temperature exhibit severe reductions in fecundity. Oogenesis in EcR mutant females is defective, and the spectrum of oogenic defects includes the presence of abnormal egg chambers and loss of vitellogenic egg stages. Our results demonstrate a requirement for EcR during female reproduction and suggest that EcR is required for normal oogenesis.

Animals↗
PubMed2000

A conditional rescue system reveals essential functions for the ecdysone receptor (EcR) gene during molting and metamorphosis in Drosophila.

In Drosophila, pulses of the steroid hormone ecdysone trigger larval molting and metamorphosis and coordinate aspects of embryonic development and adult reproduction. At each of these developmental stages, the ecdysone signal is thought to act through a heteromeric receptor composed of the EcR and USP nuclear receptor proteins. Mutations that inactivate all EcR protein isoforms (EcR-A, EcR-B1, and EcR-B2) are embryonic lethal, hindering analysis of EcR function during later development. Using transgenes in which a heat shock promoter drives expression of an EcR cDNA, we have employed temperature-dependent rescue of EcR null mutants to determine EcR requirements at later stages of development. Our results show that EcR is required for hatching, at each larval molt, and for the initiation of metamorphosis. In EcR mutants arrested prior to metamorphosis, expression of ecdysone-responsive genes is blocked and normal ecdysone responses of both imaginal and larval tissues are blocked at an early stage. These results show that EcR mediates ecdysone signaling at multiple developmental stages and implicate EcR in the reorganization of imaginal and larval tissues at the onset of metamorphosis.

Animals↗
PubMed1999

DHR3 is required for the prepupal-pupal transition and differentiation of adult structures during Drosophila metamorphosis.

Pulses of the steroid hormone ecdysone activate genetic regulatory hierarchies that coordinate the developmental changes associated with Drosophila metamorphosis. A high-titer ecdysone pulse at the end of larval development triggers puparium formation and induces expression of the DHR3 orphan nuclear receptor. Here we use both a heat-inducible DHR3 rescue construct and clonal analysis to define DHR3 functions during metamorphosis. Clonal analysis reveals requirements for DHR3 in the development of adult bristles, wings, and cuticle, and no apparent function in eye or leg development. DHR3 mutants rescued to the third larval instar also reveal essential functions during the onset of metamorphosis, leading to lethality during prepupal and early pupal stages. The phenotypes associated with these lethal phases are consistent with the effects of DHR3 mutations on ecdysone-regulated gene expression. Although DHR3 has been shown to be sufficient for early gene repression at puparium formation, it is not necessary for this response, indicating that other negative regulators may contribute to this pathway. In contrast, DHR3 is required for maximal expression of the midprepupal regulatory genes, EcR, E74B, and betaFTZ-1. Reductions in EcR and betaFTZ-F1 expression, in turn, lead to submaximal early gene induction in response to the prepupal ecdysone pulse and corresponding defects in adult head eversion and salivary gland cell death. These studies demonstrate that DHR3 is an essential regulator of the betaFTZ-F1 midprepupal competence factor, providing a functional link between the late larval and prepupal responses to ecdysone. Induction of DHR3 in early prepupae ensures that responses to the prepupal ecdysone pulse will be distinct from responses to the late larval pulse and thus that the animal progresses in an appropriate manner through the early stages of metamorphosis.

Animals↗
PubMed1999

Lipoprotein(a) stimulates growth of human mesangial cells and induces activation of phospholipase C via pertussis toxin-sensitive G proteins.

BACKGROUND: Renal disease is commonly associated with hyperlipidemia and correlates with glomerular accumulation of atherogenic lipoproteins, for example, lipoprotein(a) [Lp(a)], and mesangial hypercellularity. Specific binding of Lp(a) to mesangial cells and induction of c-myc and c-fos expression has been demonstrated. Therefore, in this study, we investigated a possible growth stimulatory effect and mode of action of Lp(a) in human mesangial cells. METHODS: Lp(a) was purified from the regenerate fluid of a dextran sulfate column-based low-density lipoprotein apheresis system. Human mesangial cells were isolated by a sequential sieving technique from patients undergoing tumor nephrectomy. DNA synthesis was measured by [3H]-thymidine incorporation. The intracellular calcium concentration ([Ca2+]i) was determined by Fura 2-fluorescence, and inositol 1,4,5-trisphosphate (1,4,5-IP3) concentration was measured by a radioreceptor assay. RESULTS: The data show that Lp(a) bound to the cells with a Kd of 17.0 micrograms/ml and increased DNA synthesis and cell proliferation. Lp(a) caused a rapid increase in 1,4,5-IP3 and [Ca2+]i via a pertussis toxin-sensitive mechanism. The phospholipase C (PLC) inhibitor U73122 abolished Lp(a)-induced cell proliferation. In contrast, vasopressin-induced increase in 1,4,5-IP3 and [Ca2+]i was pertussis toxin insensitive. CONCLUSION: This study revealed that Lp(a) stimulates growth of human mesangial cells. Lp(a)-induced signaling involves binding to a receptor and stimulation of PLC via Gi proteins. Stimulation of PLC appears to be essential for the growth stimulatory effect of Lp(a). Whether these effects of Lp(a) contribute to the pathophysiology of renal disease needs to be determined.

Blood Proteins↗
PubMed1999

Ecdysone response genes govern egg chamber development during mid-oogenesis in Drosophila.

The steroid hormone ecdysone regulates larval development and metamorphosis in Drosophila melanogaster through a complex genetic hierarchy that begins with a small set of early response genes. Here, we present data indicating that the ecdysone response hierarchy also mediates egg chamber maturation during mid-oogenesis. E75, E74 and BR-C are expressed in a stage-specific manner while EcR expression is ubiquitous throughout oogenesis. Decreasing or increasing the ovarian ecdysone titer using a temperature-sensitive mutation or exogenous ecdysone results in corresponding changes in early gene expression. The stage 10 follicle cell expression of E75 in wild-type, K10 and EGF receptor (Egfr) mutant egg chambers reveals regulation of E75 by both the Egfr and ecdysone signaling pathways. Genetic analysis indicates a germline requirement for ecdysone-responsive gene expression. Germline clones of E75 mutations arrest and degenerate during mid-oogenesis and EcR germline clones exhibit a similar phenotype, demonstrating a functional requirement for ecdysone responsiveness during the vitellogenic phase of oogenesis. Finally, the expression of Drosophila Adrenodoxin Reductase increases during mid-oogenesis and clonal analysis confirms that this steroidogenic enzyme is required in the germline for egg chamber development. Together these data suggest that the temporal expression profile of E75, E74 and BR-C may be a functional reflection of ecdysone levels and that ecdysone provides temporal signals regulating the progression of oogenesis and proper specification of dorsal follicle cell fates.

Animals↗
PubMed1999

Brains, minds and selves: changing conceptions of the losses involved in dementia.

Until the last 10 years or so, dementia research had been dominated by the psychiatric or medical approach to dementia. However, increasing numbers of new psychological and social psychological approaches to dementia have begun to emerge. Consequently, there has been a significant change in the descriptions of the losses involved in the dementing process: from being represented in terms of brain functioning, they have become repositioned as occurring within both personal and social contexts. We elaborate these frameworks and apply them to three phenomena associated with dementia--depressions, delusions and denial. While these conceptualizations are limited by a number of difficulties, they nevertheless represent a significant change in approaches to dementia care and allow the potential for positive change through psychological as well as chemical means. The emergence of these new accounts of the losses involved in dementia needs to be matched by the equivalent development of effective psychosocial interventions to maintain individuals within their own homes.

Brain↗
PubMed1998

Lipoprotein (a) stimulates mitogen activated protein kinase in human mesangial cells.

Evidence suggests an important role of elevated serum lipoproteins in the progression of renal glomerulosclerosis. We report here that lipoprotein (a) (Lp(a)) increased phosphorylation and activity of mitogen activated protein kinase (MAPK) in human mesangial cells. When protein kinase C (PKC) was depleted by long-term incubation with the phorbol 12-O-myristate 13-acetate the effect of Lp(a) on MAPK activation was completely inhibited. Forskolin, a stimulator of the adenylyl cyclase, and dibutyryl-cAMP reduced the effect of Lp(a) on MAPK phosphorylation and activation. We conclude that Lp(a) stimulates the MAPK cascade via activation of PKC and that activation of protein kinase A counteracts Lp(a) induced MAPK activation in human mesangial cells.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Plasma concentrations of soluble TNF-alpha receptors in obese subjects.

BACKGROUND: Recent studies show an increased adipose production of tumor necrosis factor-alpha (TNF-alpha) in human obesity. It was hypothesized from this finding and other data, that TNF-alpha may be a mediator of obesity-linked insulin resistance. OBJECTIVE: The aim of this study was to measure plasma concentrations of the two soluble TNF-alpha receptors, together with those of TNF-alpha in subjects with severe obesity with and without type 2 diabetes mellitus, in comparison to a lean control group, to examine whether plasma concentrations reflect an up-regulation of the TNF system in adipose tissue. PATIENTS AND METHODS: Plasma concentrations of the two soluble TNF-alpha receptors were measured in 49 obese subjects (mean body mass index (BMI): 44.9 kg/m2, 95% confidence intervals (CI) 42.3-47.5 kg/m2, including 19 type 2 diabetic individuals) and 28 lean controls, by using a highly sensitive enzyme-linked immunoassay (ELISA) technique. TNF-alpha concentrations were determined in 28 obese (10 with diabetes) and 23 lean subjects. RESULTS: The obese subjects showed significantly higher plasma concentrations of the soluble p60 and p80 TNF receptor, respectively, compared to the lean control group, independent of the presence of diabetes. Multiple regression analysis, with the p80 TNF receptor as dependent variable, revealed that BMI and log insulin significantly affected the plasma concentration of this soluble receptor subtype, explaining 46% of the variance, whereas for the p60 TNF receptor, only BMI turned out to influence plasma concentrations. TNF-alpha plasma concentrations were not different between the three groups (Kruskal-Wallis test: P=0.34), but due to the low power of the test, an effect of obesity on TNF-alpha is not excluded. CONCLUSION: These data indicate that plasma concentrations of both soluble TNF receptors are elevated in obesity and insulin resistance, possibly as a function of excess body fat. The reported adipose overexpression of TNF-alpha does not seem to be reflected by elevated plasma concentrations, suggesting a primarily local role of the cytokine.

Adult↗
PubMed1998

Serum leptin levels increase rapidly after initiation of clozapine therapy.

Weight gain is a major side-effect of treatment with clozapine. In order to investigate the influence of the atypical neuroleptic clozapine on leptin secretion, serum leptin levels were measured in 12 patients at baseline and for a 10-week period after initiation of treatment. Serum clozapine levels and levels of its metabolites were simultaneously assessed. Alterations of body weight and body composition were determined. During the 10-week observation period leptin levels differed significantly from the levels determined at baseline (P < 0.0001). During the first 2 weeks of treatment serum leptin levels at least doubled in eight of the 12 patients. The maximal relative increase over baseline was 536%. Low doses of clozapine were sufficient to induce this effect. Within a 10-week period mean body weight, mean body mass index, mean fat mass and mean lean body mass all increased. Based on the results we suggest that in predisposed individuals clozapine induces an increased appetite; overeating and weight gain can ensue, which in turn underlie elevated leptin secretion.

Adipose Tissue↗
PubMed1998

Drosophila EcR-B ecdysone receptor isoforms are required for larval molting and for neuron remodeling during metamorphosis.

During the metamorphic reorganization of the insect central nervous system, the steroid hormone 20-hydroxyecdysone induces a wide spectrum of cellular responses including neuronal proliferation, maturation, cell death and the remodeling of larval neurons into their adult forms. In Drosophila, expression of specific ecdysone receptor (EcR) isoforms has been correlated with particular responses, suggesting that different EcR isoforms may govern distinct steroid-induced responses in these cells. We have used imprecise excision of a P element to create EcR deletion mutants that remove the EcR-B promoter and therefore should lack EcR-B1 and EcR-B2 expression but retain EcR-A expression. Most of these EcR-B mutant animals show defects in larval molting, arresting at the boundaries between the three larval stages, while a smaller percentage of EcR-B mutants survive into the early stages of metamorphosis. Remodeling of larval neurons at metamorphosis begins with the pruning back of larval-specific dendrites and occurs as these cells are expressing high levels of EcR-B1 and little EcR-A. This pruning response is blocked in the EcR-B mutants despite the fact that adult-specific neurons, which normally express only EcR-A, can progress in their development. These observations support the hypothesis that different EcR isoforms control cell-type-specific responses during remodeling of the nervous system at metamorphosis.

Animals↗