Biomedical subjects

Peter Fischer

Publications and source records attributed to Peter Fischer.

At least 19 recordsLinked to original sources

PubMed2006

Conversion from cognitive health to mild cognitive impairment and Alzheimer's disease: prediction by plasma amyloid beta 42, medial temporal lobe atrophy and homocysteine.

The changes of plasma amyloid beta (Abeta42) protein, homocysteine and medial temporal lobe atrophy (MTA) were studied by the transition from cognitive health to mild cognitive impairment (MCI) and to Alzheimer's disease (AD) in a prospective cohort of individuals aged 75 years. MTA but not plasma Abeta42 measured at baseline predicted which persons remained cognitively healthy (CH) and who developed AD 2.5 years later. The increase of plasma Abeta42 over time significantly distinguished between persons who remained CH on the one hand and MCI converters and AD converters out of cognitive health on the other (CH-to-MCI and CH-to-AD converters). Although both groups showed similar increase of Abeta42 levels, CH-to-AD converters had a higher increase of homocysteine compared to CH-to-MCI converters or to persons remaining CH. In comparison to all cognitive subgroups, the AD converters from MCI at baseline showed the smallest increase of Abeta42 levels and rather no increase of homocysteine. In logistic regression analysis, the increase of plasma Abeta42 but not change of MTA significantly predicted the conversion from CH to MCI, and changes of MTA and homocysteine but not of plasma Abeta42 predicted the conversion from CH to AD. The increase of plasma Abeta42 correctly allocated CH-to-MCI and CH-to-AD converters with low (63%) specificity (for both) and low (60%) sensitivity (54% for AD group). These results indicate that (1) plasma Abeta42 alone is not suitable as a biomarker for AD, (2) in the course of cognitive deterioration of the AD-type the increase of plasma Abeta42 seems to be an initial event, (3) similar to cerebrospinal fluid, changes of plasma Abeta42 may reflect the transition from cognitive health to AD, and (4) whether persons with MCI develop AD may depend on an accumulation of further toxic metabolites such as homocysteine.

Aged↗

PubMed2006

Mathematical models and lymphatic filariasis control: monitoring and evaluating interventions.

Monitoring and evaluation are crucially important to the scientific management of any mass parasite control programme. Monitoring enables the effectiveness of implemented actions to be assessed and necessary adaptations to be identified; it also determines when management objectives are achieved. Parasite transmission models can provide a scientific template for informing the optimal design of such monitoring programmes. Here, we illustrate the usefulness of using a model-based approach for monitoring and evaluating anti-parasite interventions and discuss issues that need addressing. We focus on the use of such an approach for the control and/or elimination of the vector-borne parasitic disease, lymphatic filariasis.

Animals↗

PubMed2006

Detection of Brugia parasite DNA in human blood by real-time PCR.

Brugian filariasis (caused by the nematodes Brugia malayi and B. timori) is an important cause of disability in Southeast Asia. Improved diagnostic tests are needed for filariasis elimination programs (to identify areas of endemicity and to monitor progress) and for diagnosis of the disease in infected individuals. We have developed and evaluated two real-time PCR assays for detecting Brugia DNA in human blood and compared the results of these assays to those of "gold standard" assays. One assay uses a TaqMan probe (TaqM) to amplifiy a 320-bp "HhaI repeat" DNA sequence. The other assay uses a minor groove binding probe (MGB) and modified nucleotides in primers (Eclipse MGB) to amplify a 120-bp fragment of the HhaI repeat. This assay detects 22 copies of the target sequence, and it is more sensitive than the TaqM assay. Both assays were evaluated with human blood samples from two different areas of endemicity. The MGB assay was as sensitive as membrane filtration and microscopy for the detection of B. malayi infection in 57 blood samples recovered at night from patients in Sulawesi, Indonesia. The MGB assay also detected parasite DNA in 17 of 31 (55%) of microfilaria-negative day blood samples from these subjects. This test was more sensitive than the conventional and the TaqM PCRs (and was almost as sensitive as night blood membrane filtration) for the detection of infection in 52 blood samples recovered at night from individuals in an area of B. timori endemicity on Alor Island, Indonesia, where microfilaria-positive individuals had low densities after mass treatment. Thus, the Eclipse MGB real-time PCR assay is a sensitive means of detecting Brugia parasite DNA in human blood.

Animals↗

PubMed2006

Molecular characterization of the anti-idiotypic immune response of a relapse-free neuroblastoma patient following antibody therapy: a possible vaccine against tumors of neuroectodermal origin?

Neuroblastoma treatment with chimeric antidisialoganglioside GD2 Ab ch14.18 showed objective antitumor responses. Production of anti-idiotypic Abs (Ab2) against ch14.18 (Ab1) in some cases was positively correlated with a more favorable prognosis. According to Jerne's network theory, a subset of anti-idiotypic Abs (Ab2beta) carries an "internal image" of the Ag and induces Abs (Ab3) against the original Ag. The molecular origin of an anti-idiotypic Ab response in tumor patients was not investigated previously. To clone anti-idiotypic Abs, B cells of a ch14.18-treated neuroblastoma patient with Ab2 serum reactivity were used to construct Ab phage display libraries. After repeated biopannings on ch14.18 and its murine relative, anti-GD2 mAb 14G2a, we selected 40 highly specific clones. Sequence analysis revealed at least 10 of 40 clones with different Ig genes. Identities to putative germline genes ranged between 94.90 and 100% for V(H) and between 93.90 and 99.60% for V(L). An overall high rate of replacement mutations suggested a strong Ag-driven maturation of the anti-idiotypic Abs. Two clones that were analyzed further, GK2 and GK8, inhibited binding of ch14.18 to GD2 just as the patient's serum did. GK8 alone inhibited >80% of the patient's anti-idiotypic serum Abs in binding to ch14.18. Rabbits vaccinated with GK8 or GK2 (weaker) produced Ab3 against the original target Ag GD2. GK8 may be useful as a tumor vaccine for GD2-positive [corrected] tumors.

Amino Acid Sequence↗

PubMed2006

Single-element objective lens for soft x-ray differential interference contrast microscopy.

High-resolution soft x-ray differential interference contrast (DIC) imaging was demonstrated through the use of a single-element objective, the XOR pattern, in a full-field soft x-ray microscope. DIC images of the magnetic domains in a 59 nm thick amorphous Gd25Fe75 layer were obtained and magnetic phase contributions were directly imaged. With its elemental, chemical, and magnetic specificity, compatibility with various sample environments, and ease of implementation, we expect this soft x-ray DIC technique to become one of the standard modes of operation for existing full-field soft x-ray microscopes.

Journal Article↗

PubMed2006

Three-dimensional modeling of mechanical forces in the extracellular matrix during epithelial lumen formation.

Mechanical interactions between cells and extracellular matrix (ECM) mediate epithelial cyst formation. This work relies on the combination of numerical modeling with live cell imaging, to piece together a novel nonintrusive method for determining three-dimensional (3D) mechanical forces caused by shape changes of a multicellular aggregate at the early stages of epithelial cyst formation. We analyzed the evolution of Madin-Darby canine kidney cells in 3D cultures using time-lapse microscopy, with type I collagen gel forming the ECM. The evolving 3D interface between the ECM and the cell aggregate was obtained from microscopy images, and the stress on the surface of a proliferating aggregate and in the surrounding ECM was calculated using the finite element method. The viscoelastic properties of the ECM (a needed input for the finite element method solver) were obtained through oscillatory shear flow experiments on a rheometer. For validation purpose, the forces exerted by an aggregate on a force-sensor array were measured and compared against the computational results.

Animals↗

PubMed2006

Estimation of the prevalence of lymphatic filariasis by a pool screen PCR assay using blood spots collected on filter paper.

The prevalence of lymphatic filariasis was estimated by PCR-based pool screening of night blood collected from 865 individuals living in ten areas endemic for Wuchereria bancrofti, Brugia malayi or B. timori in Indonesia. A total of 232 microfilaraemics were identified by filtration of 1 ml of blood. The microfilaria (mf) prevalence ranged from 6% to 54%, and the mf density in microfilaraemics ranged from 1 mf/ml to 6028 mf/ml. PCR assays both for W. bancrofti or Brugia spp. detected a single mf present on a 30 microl dried filter paper blood spot. One hundred and seventy-eight pools of five blood spots in each pool (pool-5) were tested by PCR and 101 (57%) pools were positive. When pool size was increased to 10 spots per pool (pool-10), 65 (70%) of 93 pools were positive. Pearson's correlation and linear regression showed a strong correlation between filtration and pool screen PCR results for pool-10 (r=0.835) and pool-5 (r=0.695). Based on the determination coefficient (R), the results of pool-10 PCR (R=0.697) gave a better prediction compared with pool-5 PCR (R=0.483). This study suggests that pool screen PCR may be a useful tool for monitoring the Global Program to Eliminate Lymphatic Filariasis.

Adolescent↗

PubMed2006

Terror management and religion: evidence that intrinsic religiousness mitigates worldview defense following mortality salience.

Terror management theory suggests that people cope with awareness of death by investing in some kind of literal or symbolic immortality. Given the centrality of death transcendence beliefs in most religions, the authors hypothesized that religious beliefs play a protective role in managing terror of death. The authors report three studies suggesting that affirming intrinsic religiousness reduces both death-thought accessibility following mortality salience and the use of terror management defenses with regard to a secular belief system. Study 1 showed that after a naturally occurring reminder of mortality, people who scored high on intrinsic religiousness did not react with worldview defense, whereas people low on intrinsic religiousness did. Study 2 specified that intrinsic religious belief mitigated worldview defense only if participants had the opportunity to affirm their religious beliefs. Study 3 illustrated that affirmation of religious belief decreased death-thought accessibility following mortality salience only for those participants who scored high on the intrinsic religiousness scale. Taken as a whole, these results suggest that only those people who are intrinsically vested in their religion derive terror management benefits from religious beliefs.

Adaptation, Psychological↗

PubMed2006

Using knowledge, attitudes and practice (KAP) surveys on lymphatic filariasis to prepare a health promotion campaign for mass drug administration in Alor District, Indonesia.

We report the results of two surveys of people's knowledge, attitudes and practices (KAP) regarding lymphatic filariasis (LF) in Alor District, eastern Indonesia. The results of the surveys were used to prepare and evaluate the social mobilization component of a pilot mass drug administration (MDA) in five villages. In the study area, the filarial parasites Brugia timori and Wuchereria bancrofti are highly endemic. Frequent and severe adverse reactions after MDA may occur especially in areas endemic for B. timori and therefore, a special communication strategy was designed to inform and to educate communities about LF and its control. The first KAP survey was conducted as a baseline pre-MDA with diethylcarbamazine and albendazole and the second as a post-intervention evaluation in order to obtain information on the impact of the communication campaign. Before the information campaign and the subsequent MDA, 54% of the study population had heard of one of the three main terms for LF, whereas after health education and MDA, 89% had heard of at least one of the three terms. Similarly, pre-MDA, 21% reported having had previously taken the treatment for filariasis, while post-MDA, 88% reported having taken the treatment during the pilot treatment period. The historical fears and traumatic experiences associated with past LF treatment campaigns in Indonesia were averted since both the communication campaign and the MDA were designed appropriately for and together with the community. As a result, compliance was sufficient in the first round to successfully begin the elimination process.

Adolescent↗

PubMed2006

Coping with terrorism: the impact of increased salience of terrorism on mood and self-efficacy of intrinsically religious and nonreligious people.

It was hypothesized that intrinsic religiousness helps to cope with increased salience of terrorism. Intrinsically religious and non-religious participants were told that it is highly probable or highly improbable, respectively, that terrorist attacks will occur in Germany. High probability of terrorism only negatively affected the mood of non-religious participants but not of intrinsically religious participants (Study 1). Using as a realistic context of investigation the terrorist suicide bombings in Istanbul, the authors replicated this finding and shed some light on the underlying psychological processes (Study 2): On the day of the terrorist attacks (high salience of terrorism), non-religious participants experienced less positive emotions and less self-efficacy than did intrinsically religious participants. Two months later (low salience of terrorism), no differences were found between non-religious and intrinsically religious participants with regard to mood and self-efficacy. Mediational analyses suggested that the mood effects were associated with differences in the reported sense of self-efficacy.

Adaptation, Psychological↗

PubMed2006

Music and aggression: the impact of sexual-aggressive song lyrics on aggression-related thoughts, emotions, and behavior toward the same and the opposite sex.

Three studies examined the impact of sexual-aggressive song lyrics on aggressive thoughts, emotions, and behavior toward the same and the opposite sex. In Study 1, the authors directly manipulated whether male or female participants listened to misogynous or neutral song lyrics and measured actual aggressive behavior. Male participants who were exposed to misogynous song lyrics administered more hot chili sauce to a female than to a male confederate. Study 2 shed some light on the underlying psychological processes: Male participants who heard misogynous song lyrics recalled more negative attributes of women and reported more feelings of vengeance than when they heard neutral song lyrics. In addition, men-hating song lyrics had a similar effect on aggression-related responses of female participants toward men. Finally, Study 3 replicated the findings of the previous two studies with an alternative measure of aggressive behavior as well as a more subtle measure of aggressive cognitions. The results are discussed in the framework of the General Aggression Model.

Adolescent↗

PubMed2006

Clinical chemistry reference values for 75-year-old apparently healthy persons.

BACKGROUND: Clinical chemistry reference values for elderly persons are sparse and mostly intermixed with those for younger subjects. To understand the links between metabolism and aging, it is paramount to differentiate between "normal" physiological processes in apparently healthy elderly subjects and metabolic changes due to long-lasting diseases. The Vienna Transdanube Aging (VITA) study, which began in 2000 and is continuing, will allow us to do just that, because more than 600 male and female volunteers aged exactly 75 years (to exclude any influence of the "aging" factor in this cohort) are participating in this study. METHODS: Extensive clinical, neurological, biochemical, psychological, genetic, and radiological analyses, with a special emphasis on consumption of medication and abuse of drugs, were performed on each of the probands. The multitude of data and questionnaires obtained made possible an a posteriori approach to select individuals fulfilling criteria for a reference sample group of apparently healthy 75-year-old subjects for our study. Specific analytes were quantified on automated clinical analyzers, while manual methods were used for hormonal analytes. All clinical chemistry analytes were evaluated using in-depth statistical analyses with SPSS for Windows. RESULTS: In all, reference intervals for 45 analytes could be established. These include routine parameters for the assessment of organ functions, as well as hormone concentrations and hematological appraisals. Because all patients were reevaluated after exactly 30 months in the course of this study, we had the opportunity to reassess their health status at the age of 77.5 years. This was very useful for validation of the first round data set. Data of the second round evaluation corroborate the reference limits of the baseline analysis and further confirm our inclusion and exclusion criteria. CONCLUSIONS: In summary, we have established a reliable set of reference data for hormonal, hematological, and clinical chemistry analytes for elderly subjects. These values will be very useful for our future attempts to correlate disease states and aging processes with metabolic factors.

Aged↗

PubMed2006

Association study of the 5-HTTLPR polymorphism and depression in 75-Year-Old nondemented subjects from the Vienna Transdanube Aging (VITA) study.

BACKGROUND: The site of effect for the selective serotonin reuptake inhibitors (SSRIs) is the serotonin transporter (5-HTT), which is extensively investigated for its involvement in depressive symptoms. The 5-HTT gene exhibits a 5'-promoter-based length polymorphism (5-HTTLPR) that affects the transcription efficiency and activity, known as short (S) and long (L) alleles. We studied the association of this polymorphism in old age and depression in the Vienna Transdanube Aging (VITA) study, excluding subjects with dementia. METHOD: We used retrospective data from the baseline of the VITA study, which is a cohort study of all inhabitants of a geographical area aged 75 years (N = 544). Depression was diagnosed and classified strictly according to the DSM-IV. To eliminate dementia effects, we excluded subjects with a Clinical Dementia Rating higher than or equal to 1 and/or a Mini-Mental State Examination score lower than 24. Genotyping for the 5-HTTLPR L/S allele was conducted using polymerase chain reaction methodology. RESULTS: We found significantly higher SS genotype frequency in all subjects with past/ present depression compared to controls (trend test, p = .01). The SS genotype frequency was especially high in subjects with onset of depression before age 65. No correlations were found between genotypes/S allele carriers and actual Hamilton Rating Scale for Depression, Short-Geriatric Depression Scale, and anxiety scale scores. CONCLUSIONS: These observations of higher frequency of the 5-HTTLPR S allele in subjects with past/present depression fit with previous findings and point to the important role of 5-HTT in depression.

Aged↗

PubMed2005

Sorbitan tristearate layers at the air/water interface studied by shear and dilatational interfacial rheology.

The shear and dilatational rheology of condensed interfacial layers of the water-insoluble surfactant sorbitan tristearate at the air/water interface is investigated. A new interfacial shear rheometer allows measurements in both stress- and strain-controlled modes, providing comprehensive interfacial rheological information such as the interfacial dynamic shear moduli, the creep response to a stress pulse, the stress relaxation response to a strain step, or steady shear curves. Our experiments show that the interfacial films are both viscoelastic and brittle in nature and subject to fracture at small deformations, as was supported by in-situ Brewster angle microscopy performed during the rheological experiments. Although any large-deformation test is destructive to the sample, it is still possible to study the linear viscoelastic regime if the deformations involved are controlled carefully. Complementary results for the dilatational rheology in area step compression/expansion experiments are reported. The dilatational behavior is predominantly elastic throughout the frequency spectrum measured, whereas the layers exhibit generalized Maxwell behavior in shear mode within a deformation frequency regime as narrow as two decades, indicating the presence of additional relaxation mechanisms in shear as opposed to expansion/compression. If the transient rheological response from stress relaxation experiments is considered, then the data can be described well with a stretched exponential model both in the shear and dilatational deformations.

Air↗

PubMed2005

The highly abundant protein Ag-lbp55 from Ascaridia galli represents a novel type of lipid-binding proteins.

Lipid-binding proteins exhibit important functions in lipid transport, cellular signaling, gene transcription, and cytoprotection. Their functional analogues in nematodes are nematode polyprotein allergens/antigens and fatty acid and retinoid-binding proteins. This work describes a novel 55-kDa protein, Ag-lbp55, purified from the parasitic nematode Ascaridia galli. By direct N-terminal sequencing, a partial amino acid sequence was obtained that allowed the design of oligonucleotide primers to obtain the full-length cDNA sequence. Sequence analysis revealed the presence of an N-terminal signal peptide of 25 amino acid residues and a FAR domain at the C terminus. Data base searches showed almost no significant homologies to other described proteins. The secondary structure of Ag-lbp55 was predominantly alpha-helical (65%) as shown by CD spectroscopy. It was found to bind with high affinity fatty acids (caprylic, oleic, and palmitic acid) and their fluorescent analogue dansylaminoundecanic acid. Immunolocalization showed that Ag-lbp55 is a highly abundant protein, mainly distributed in the inner hypodermis and extracellularly in the pseudocoelomatic fluid. A similar staining pattern was observed in other pathogenic nematodes, indicating the existence of similar proteins in these species.

Amino Acid Sequence↗

PubMed2005

Stress driven shear bands and the effect of confinement on their structures--a rheological, flow visualization, and Rheo-SALS study.

An equimolar mixture of a cationic surfactant, cetylperidinium chloride (CPyCl), and salt sodium salicylate (NaSal) forms wormlike micelles in aqueous solutions. Under shear, the solution shows a pronounced shear-thickening behavior, which is coupled with oscillations in shear rate and the apparent viscosity. In this shear-thickening regime shear bands form, which also oscillate in position and intensity. These shear bands are visualized by direct imaging and Rheo-small angle light scattering methods. Temporal intensity fluctuations of the shear bands were evaluated using image analysis. Fourier transformations (FT) of the oscillating shear rate and intensity of the shear bands showed a single dominating frequency in the power spectrum analysis. This characteristic frequency as well as the amplitude of shear rate fluctuation was found to increase with stress. From the rheological and optical measurements, we propose that a stress driven mechanism is responsible for the formation of shear bands. Experiments performed in transparent parallel-plate geometry show dampening of the shear rate oscillations and increase in the characteristic frequency with decrease in the gap. Power spectrum analysis and the SALS measurements confirm the formation of different structures as a function of gap size in the parallel-plate geometry.

Journal Article↗

PubMed2005

Structure of free MDM2 N-terminal domain reveals conformational adjustments that accompany p53-binding.

Critical to the inhibitory action of the oncogene product, MDM2, on the tumour suppressor, p53, is association of the N-terminal domain of MDM2 (MDM2N) with the transactivation domain of p53. The structure of MDM2N was previously solved with a p53-derived peptide, or small-molecule ligands, occupying its binding cleft, but no structure of the non-liganded MDM2N (i.e. the apo-form) has been reported. Here, we describe the solution structure and dynamics of apo-MDM2N and thus reveal the nature of the conformational changes in MDM2N that accompany binding of p53. The new structure suggests that p53 effects displacement of an N-terminal segment of apo-MDM2N that occludes access to the shallow end of the p53-binding cleft. MDM2N must also undergo an expansion upon binding, achieved through a rearrangement of its two pseudosymetrically related sub-domains resulting in outward displacements of the secondary structural elements that comprise the walls and floor of the p53-binding cleft. MDM2N becomes more rigid and stable upon binding p53. Conformational plasticity of the binding cleft of apo-MDM2N could allow the parent protein to bind specifically to several different partners, although, to date, all the known liganded structures of MDM2N are highly similar to one another. The results indicate that the more open conformation of the binding cleft of MDM2N observed in structures of complexes with small molecules and peptides is a more suitable one for ligand discovery and optimisation.

Animals↗

PubMed2005

Impact of two rounds of mass drug administration using diethylcarbamazine combined with albendazole on the prevalence of Brugia timori and of intestinal helminths on Alor Island, Indonesia.

BACKGROUND: Annual mass drug administration (MDA) using diethylcarbamizine (DEC, 6 mg/kg) combined with albendazole (alb, 400 mg) is recommended by the Global Programme to Eliminate Lymphatic Filariasis (GPELF). This strategy has been shown to be efficient in the of control bancroftian filariasis, but data on brugian filariasis as well as on the positive side effects on intestinal helminths are lacking. METHODS: The effect of one selective treatment and two rounds of MDA using DEC and alb on the prevalence and intensity of Brugia timori infection were studied on Alor island using a cross-sectional and a cohort approach. Before the campaign and ten months after each treatment cycle microfilariae (mf) were assessed by filtration of night blood. Before and ten months after MDA, stool samples were collected and the prevalence of intestinal helminths were determined. RESULTS: In all, the mf-rate dropped from 26.8% before any treatment to 3.8% following the second MDA. Almost all mf-positive, treated individuals showed very low mf densities. The crude prevalence of hookworm dropped from 25.3% to 5.9%. The reduction of prevalence of Ascaris lumbricoides (32.3% to 27.6%) and Trichuris trichiura (9.4% to 8.9%) was less pronounced. Within a cohort of 226 individuals, which was examined annually, the prevalence of A. lumbricoides dropped from 43.8% to 26.5% and of T. trichiura from 12.8% to 6.6%. The results indicate that this MDA approach reduces not only the mf prevalence of B. timori but also the prevalence of hookworm and to a lesser extent also of A. lumbricoides and T. trichiura. CONCLUSION: The MDA using DEC and alb as recommended by GPELF is extremely effective for areas with brugian filariasis. The beneficial effect of MDA on intestinal helminths may strengthen the national programme to eliminate lymphatic filariasis in Indonesia and may set resources free which are otherwise used for deworming campaigns of schoolchildren.

Journal Article↗