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Biomedical subjects

K Schneider

Publications and source records attributed to K Schneider.

At least 19 recordsLinked to original sources

[The early history of transmissible spongiform encephalopathies exemplified by scrapie].

Transmissible spongiform encephalopathies (TSE) are unique diseases in that they are sporadic, hereditary, and infectious. The transmissible pathogen--the prion--stands out from all other pathogens in being devoid of nucleic acids. Instead its most important and possibly only constituent is a host-encoded protein, the prion protein (PrP), in an alternative conformation induced by post-translational modifications. Thus TSEs belong to and are so far the only transmissible member of the continuously growing group of disorders collectively referred to as protein conformational disorders. During elucidation of these disorders, many different--and contradictory--theories have been put forward. Early researchers, mostly driven by the economic effect of these diseases upon sheep farming, engaged in heavy disputes concerning the heredity vs infectivity of scrapie. After the experimental demonstration of scrapie's infectivity during the twentieth century, research focused on elucidating the nature of the transmissible agent. The current work comprehensively summarizes the early literature available on TSE research.

Animals↗

Classification of non-bacterial osteitis: retrospective study of clinical, immunological and genetic aspects in 89 patients.

OBJECTIVE: To define non-bacterial osteitis (NBO) as a clinical entity possibly associated with autoimmune manifestations. Patients with sterile osteitis were analysed to develop diagnostic criteria. METHODS: A total of 89 patients with non-bacterial inflammatory bone lesions were observed for a median of 49 months. History, diagnostic imaging, laboratory and histological data were obtained. Mutation analysis in the genes PSTPIP1 and PSTPIP2 was performed. RESULTS: Patients had an onset of disease at a median age of 10 yrs [interquartile range (IQR) 7.5-12] and suffered a median period of 21 (IQR 9-52) months with a median of three foci per patient. Twenty percent of all the patients demonstrated associated autoimmune disorders, particularly of the skin and bowel. The majority of bone lesions were located in the vertebrae and metaphyses. Slight-to-moderate elevation of inflammation values were found in all the patients and antinuclear antibodies were elevated in 30%. Non-steroidal anti-inflammatory drugs (NSAIDs) were effective in 85% of the patients. HLA-B27 and Human Leukocyte Antigen-DR (HLA-DR)-classification did not differ from the general population. Autoimmune diseases in 40% of all the families, multiply affected family members, linkage to 18q21 and mouse models strongly indicate a genetic basis for NBO. We observed three different courses of disease regarding the duration of complaints, rate of complications and associated autoimmune manifestations leading to a new classification of NBO. CONCLUSIONS: Clinical analysis of our cohort leads us to define NBO as a distinct disease entity with three clinical presentations: acute NBO, chronic recurrent multifocal osteomyelitis or persistent chronic NBO. Diagnostic criteria were proposed to differentiate NBO from diseases with similar clinical presentation.

Adaptor Proteins, Signal Transducing↗

[Typical findings of maltreated children].

Childhood maltreatment manifests in a variety of forms and the underlying causes are manifold. In contrast to other offences involving physical injury, reporting behavior has, statistically speaking, remained unchanged. Patterns of injury must first be established and documented, and this involves a complete examination of the child's body. Depending on the constellation of findings, a radiological diagnosis is usually necessary. When all the findings have been collected, the further steps to be taken--where indicated a report to the police--must be discussed. All the evidence must be recorded, and photos obtained of all externally visible injuries before they fade. It is not the task of the physician to develop criminalistic ambitions, for example, by grilling (a parent) on the cause of the injuries. However, he/she has a duty to do everything necessary to protect the well-being of the child.

Child↗

[Significance of PET and integrated PET/CT in the diagnostics of occult primary tumors].

BACKGROUND: In the last years (18)F-FDG-positron-emission-tomography (PET) worked satisfactorily as helpful auxiliary method in order to verify recurrency of head and neck tumors and to detect primary tumors in case of CUP syndrome especially when CT and MR imaging failed to identify the tumor accurately. Fusion of FDG hypermetabolism in PET scan and anatomical structures is achieved by integrating positron emission tomography with CT and provides improvement also in case of CUP syndrome. This retrospective study shows 47 patients with neck metastases where PET or PET/CT helped to detect primary tumor site. PATIENTS: In a retrospective investigation 49 PET studies of 47 patients with CUP syndrome were analyzed. RESULTS: 9 cases had positive PET findings, 1 case false-positive. 5 cases were false-negative. In 40 PET studies there couldn't be found any sign of suspicious FDG hypermetabolism. CONCLUSION: PET and PET/CT deliver a certain improvement in localization of primary tumor site and therapeutical strategy.

Adult↗

[Ointments and other dermal applications].

In dermatopharmacotherapy the choice of the appropriate vehicle is essential. Acuity of the efflorescence, localization, and extent of the affection, skin type, cosmetic preferences of the patient as well as removability with water, cooling and occlusive effects of the vehicle are important criteria for the choice of the appropriate vehicle. Adapted therapeutic and utilization modalities support a successful dermatopharmacotherapy and compliance.

Administration, Topical↗

[The integrated PET/CT: technological advance in diagnostics of head and neck recurrencies and CUP?].

BACKGROUND: In the last years (18)F-Fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) worked satisfactorily as auxiliary method in order to show recurrency of head and neck tumors and to detect primary tumors in case of CUP especially when CT and MR imaging failed to identify the tumor accurately. The correlation of FDG hypermetabolism and anatomical structures is now provided by a new technology which is integrating PET and CT: Integrated PET/CT represents a new technical development, which combines the advantages of CT and PET. PATIENTS: In a retrospective investigation 84 non selected PET/CT studies of 83 patients with recurrent head and neck disease and CUP were critically analyzed. RESULTS: 33 cases had positive PET findings. 5 of these 33 cases showed false-positive findings. In 51 PET studies there was not found any sign of suspicious FDG hypermetabolism. CONCLUSION: Integrated PET/CT delivers substantial progress in detecting tumor localization. False positive findings have to be considered and therefore indications should be strictly limited to special cases of head and neck tumor recurrency, cases with complex anatomical sites and CUP.

Adult↗

Patterns of growth and body condition in sea otters from the Aleutian archipelago before and after the recent population decline.

1. Growth models for body mass and length were fitted to data collected from 1842 sea otters Enhydra lutris shot or live-captured throughout south-west Alaska between 1967 and 2004. Growth curves were constructed for each of two main year groups: 1967-71 when the population was at or near carrying capacity and 1992-97 when the population was in steep decline. Analyses of data collected from animals caught during 2004, when the population density was very low, were precluded by a small sample size and consequently only examined incidentally to the main growth curves. 2. Growth curves demonstrated a significant increase in body mass and body length at age in the 1990s. Asymptotic values of body mass were 12-18% higher in the 1990s than in the 1960s/70s, and asymptotic values for body length were 10-11% higher between the same periods. Data collected in 2004 suggest a continued increase in body size, with nearly all data points for mass and length falling significantly above the 1990s growth curves. 3. In addition to larger asymptotic values for mass and length, the rate of growth towards asymptotic values was more rapid in the 1990s than in the 1960s/70s: sea otters reached 95% of asymptotic body mass and body length 1-2 years earlier in the 1990s. 4. Body condition (as measured by the log mass/log length ratio) was significantly greater in males than in females. There was also an increasing trend from the 1960s/70s through 2004 despite much year-to-year variation. 5. Population age structures differed significantly between the 1960s/70s and the 1990s with the latter distribution skewed toward younger age classes (indicating an altered lx function) suggesting almost complete relaxation of age-dependent mortality patterns (i.e. those typical of food-limited populations). 6. This study spanned a period of time over which the population status of sea otters in the Aleutian archipelago declined precipitously from levels at or near equilibrium densities at some islands in the 1960s/70s to < 5% of estimated carrying capacity by the late 1990s. The results of this study indicate an improved overall health of sea otters over the period of decline and suggest that limited nutritional resources were not the cause of the observed reduced population abundance. Our findings are consistent with the hypothesis that the decline was caused by increased killer whale predation.

Aging↗

No evidence for the 'Meselson effect' in parthenogenetic oribatid mites (Oribatida, Acari).

It has been hypothesized that in ancient apomictic, nonrecombining lineages the two alleles of a single copy gene will become highly divergent as a result of the independent accumulation of mutations (Meselson effect). We used a partial sequence of the elongation factor-1alpha (ef-1alpha) and the heat shock protein 82 (hsp82) genes to test this hypothesis for putative ancient parthenogenetic oribatid mite lineages. In addition, we tested if the hsp82 gene is fully transcribed by sequencing the cDNA and we also tested if there is evidence for recombination and gene conversion in sexual and parthenogenetic oribatid mite species. The average maximum intra-specific divergence in the ef-1alpha was 2.7% in three parthenogenetic species and 8.6% in three sexual species; the average maximum intra-individual genetic divergence was 0.9% in the parthenogenetic and 6.0% in the sexual species. In the hsp82 gene the average maximum intra-individual genetic divergence in the sexual species Steganacarus magnus and in the parthenogenetic species Platynothrus peltifer was 1.1% and 1.2%, respectively. None of the differences were statistically significant. The cDNA data indicated that the hsp82 sequence is transcribed and intron-free. Likelihood permutation tests indicate that ef-1alpha has undergone recombination in all three studied sexual species and gene conversion in two of the sexual species, but neither process has occurred in any of the parthenogenetic species. No evidence for recombination or gene conversion was found for sexual or parthenogenetic oribatid mite species in the hsp 82 gene. There appears to be no Meselson effect in parthenogenetic oribatid mite species. Presumably, their low genetic divergence is due to automixis, other homogenizing mechanisms or strong selection to keep both the ef-1alpha and the hsp82 gene functioning.

Animals↗

Impact of endodontic treatments on the rigidity of the root.

The destabilizing effect of endodontic treatment upon teeth is still controversial. The purpose of this study was to investigate the effects of different steps of endodontic treatments upon the rigidity of teeth. Extracted untreated central maxillary anterior teeth were loaded (3.75 N), and deformations of the root were assessed by Speckle pattern interferometry. The following treatments (with subsequent determination of deformability) were conducted sequentially: access preparation, manual instrumentation (Kerr files ISO-40, ISO-60, ISO-80, ISO-110), and tapered and parallel-sided post preparation. It was found that the teeth were increasingly destabilized by any treatment. While the increased deformability was not significant with the manual enlargement (p > 0.05), we found a significant destabilization after access preparation and post preparation (p < 0.05). A corresponding difference was found after conversion of the post preparation from tapered to parallel-sided (p < 0.05). Both substance loss and modifications of the natural root canal geometry play an important role in tooth rigidity.

Bicuspid↗

Bradykinin mediates phosphorylation of eNOS in odontoblasts.

While the activation of eNOS by Akt/PKB-dependent phosphorylation, leading to NO release, and the inhibition of enzyme activity by bradykinin (BK)-mediated phosphorylation of eNOS in endothelial cells are established, the phosphorylation of eNOS in odontoblasts is unknown. To clarify the regulation of eNOS in odontoblasts by BK, we examined the phosphorylation of eNOS, Akt/PKB, and ERK1/2 in odontoblasts of rat molars. BK (10(-7) M) transiently induced the phosphorylation of eNOS at Ser1177, Akt/PKB in odontoblasts, while it induced the phosphorylation of eNOS at Thr495 throughout the entire period of BK treatment. BK receptor 2 antagonist HOE 140 (10(-6) M) significantly reduced signal intensities of phosphorylated-eNOS at Ser1177, Thr495, and phosphorylated-Akt/PKB. These results suggest that BK has dual effects on the activation of eNOS in odontoblasts, the Akt/PKB-dependent up-regulation of eNOS by the transient phosphorylation at Ser1177, and the ERK1/2-independent down-regulation of eNOS by the phosphorylation at Thr495.

Animals↗

Oribatid mites as potential vectors for soil microfungi: study of mite-associated fungal species.

The ability of soil-living oribatid mites to disperse fungal propagules on their bodies was investigated. Classical plating methods were applied to cultivate these fungi and to study their morphology. Molecular markers were used for further determination. The nuclear ribosomal large subunit and the nuclear ribosomal internal transcribed spacer of DNA extracts of the cultured fungi as well as total DNA extracts of the mites themselves, also containing fungal DNA, were amplified and sequenced. Based on phylogenetic analysis, a total of 31 fungal species from major fungal groups were found to be associated with oribatid mites, indicating that mites do not selectively disperse specific species or species groups. The detected taxa were mainly saprobiontic, cosmopolitan (e.g., Alternaria tenuissima), but also parasitic fungi (Beauveria bassiana) for whose dispersal oribatid mites might play an important role. In contrast, no mycorrhizal fungi were detected in association with oribatid mites, indicating that their propagules are dispersed in a different way. In addition, fungi that are known to be a preferred food for oribatid mites such as the Dematiacea were not detected in high numbers. Results of this study point to the potential of oribatid mites to disperse fungal taxa in soil and indicate that co-evolutionary patterns between oribatid mites and their associated fungi might be rare or even missing in most cases, since we only detected ubiquitous taxa attached to the mites.

Animals↗

A probabilistic effect assessment model for hazardous substances at the workplace.

A major problem in risk assessment is the quantification of uncertainties. A probabilistic model was developed to consider uncertainties in the effect assessment of hazardous substances at the workplace. Distributions for extrapolation factors (time extrapolation, inter- and intraspecies extrapolation) were determined on the basis of appropriate empirical data. Together with the distribution for the benchmark dose obtained from substance-specific dose-response modelling for the exemplary substances 2,4,4-trimethylpentene (TMP) and aniline, they represent the input distributions for probabilistic modelling. These distributions were combined by Monte Carlo simulation. The resulting target distribution describes the probability that an aspired protection level for workers is achieved at a certain dose and the uncertainty associated with the assessment. In the case of aniline, substance-specific data on differences in susceptibility (between species; among humans due to genetic polymorphisms of N-acetyltransferase) were integrated in the model. Medians of the obtained target distributions of the basic models for TMP and aniline, but not of the specific aniline model are similar to deterministically derived reference values. Differences of more than one order of magnitude between the medians and the 5th percentile of the target distributions indicate substantial uncertainty associated with the effect assessment of these substances. The probabilistic effect assessment model proves to be a practical tool to integrate quantitative information on uncertainty and variability in hazard characterisation.

Alkenes↗

Breakable stent for interventions in infants and neonates: an animal study and histopathological findings.

OBJECTIVE: To test in a neonatal animal model the feasibility and biocompatibility of a new breakable stent that can be broken open by balloon dilatation during reintervention for use in neonates and infants. MATERIALS AND METHODS: Medical grade stainless steel breakable stents (n = 16) were interventionally implanted in systemic arteries in neonatal piglets (n = 7). Patency of the stented segments was shown by repeated angiography. Stents were redilated up to three times. After a follow up of 18-165 days the animals were killed and the tissue block containing the stent was excised. Besides standard histological examination, scanning electron microscopy was used for biocompatibility screening. RESULTS: The stents were broken by redilatation with a conventional angioplasty balloon catheter. During follow up, patency of all stented segments was shown angiographically. One stent became dislocated during implantation. One vessel ruptured during redilatation when an inadequately large balloon catheter was used for dilatation. No other complications were observed. Scanning electron microscopy showed complete cellular coverage of the stent struts. Histological examination showed thinning of the vessel wall and partial rupture of the media at the site of stent breakage. An only mild inflammatory reaction was detected. CONCLUSION: The new breakable stent can be broken open by simple angioplasty. Feasibility, effectiveness, and biocompatibility were shown in an animal model. Surgery to remove stents from paediatric patients due to disproportion between a previously implanted stent and the growing vessel may be avoided by the use of a breakable stent.

Animals↗

NO-cGMP signaling molecules in cells of the rat molar dentin-pulp complex.

By the formation of cyclic guanosine 3',5'-monophosphate (cGMP), nitric oxide (NO)-sensitive enzyme-soluble guanylate cyclase (sGC) plays a receptor role for NO within the NO-cGMP signaling cascade, which is involved in vasodilatation and neurotransmission. The hypothesis that NO-cGMP signaling molecules modulate cells of the dentin-pulp complex was investigated in rat molars by histochemical, immunohistochemical, immuno-ultrastructural, and organ bath techniques. NO synthase (NOS) I-III, the sGC alpha(2)-subunit/beta(1)-subunit, and cGMP were detected in odontoblasts and blood vessels. NOS I, sGC alpha(2), and cGMP were identified in nerve fibers. Treatment of rat molars with the NO donor NONOate (10(-5) M) increased cGMP staining intensities in blood vessels and odontoblasts, while NO synthase inhibitor L-NAME (10(-4) M) attenuated intensity of the reaction products for cGMP, suggesting an effect of endogenous NO on sGC. These correlations of patterns and alterations of cGMP staining intensities after treatment with the NO donor or NO inhibitor might represent an NO-sGC-cGMP signaling-dependent modulation of odontoblasts, blood vessels, and nerve fibers in the dentin-pulp complex.

Animals↗

Micromotor endoscope catheter for in vivo, ultrahigh-resolution optical coherence tomography.

A distally actuated, rotational-scanning micromotor endoscope catheter probe is demonstrated for ultrahigh-resolution in vivo endoscopic optical coherence tomography (OCT) imaging. The probe permits focus adjustment for visualization of tissue morphology at varying depths with improved transverse resolution compared with standard OCT imaging probes. The distal actuation avoids nonuniform scanning motion artifacts that are present with other probe designs and can permit a wider range of imaging speeds. Ultrahigh-resolution endoscopic imaging is demonstrated in a rabbit with <4-microm axial resolution by use of a femtosecond Cr:forsterite laser light source. The micromotor endoscope catheter probe promises to improve OCT imaging performance in future endoscopic imaging applications.

Animals↗

Quantitative relationship between the local lymph node assay and human skin sensitization assays.

The local lymph node assay (LLNA) is a new test method which allows for the quantitative assessment of sensitizing potency in the mouse. Here, we investigate the quantitative correlation between results from the LLNA and two human sensitization tests--specifically, human repeat insult patch tests (HRIPTs) and human maximization tests (HMTs). Data for 57 substances were evaluated, of which 46 showed skin sensitizing properties in human tests, whereas 11 yielded negative results in humans. For better comparability data from mouse and human tests were transformed to applied doses per skin area, which ranged over four orders of magnitude for the substances considered. Regression analysis for the 46 human sensitizing substances revealed a significant positive correlation between the LLNA and human tests. The correlation was better between LLNA and HRIPT data (n=23; r=0.77) than between LLNA and HMT data (n=38; r=0.65). The observed scattering of data points is related to various uncertainties, in part associated with insufficiencies of data from older HMT studies. Predominantly negative results in the LLNA for another 11 substances which showed no skin sensitizing activity in human maximization tests further corroborate the correspondence between LLNA and human tests. Based on this analysis, the LLNA can be considered a reliable basis for relative potency assessments for skin sensitizers. Proposals are made for the regulatory exploitation of the LLNA: four potency groups can be established, and assignment of substances to these groups according to the outcome of the LLNA can be used to characterize skin sensitizing potency in substance-specific assessments. Moreover, based on these potency groups, a more adequate consideration of sensitizing substances in preparations becomes possible. It is proposed to replace the current single concentration limit for skin sensitizers in preparations, which leads to an all or nothing classification of a preparation as sensitizing to skin ("R43") in the European Union, by differentiated concentration limits derived from the limits for the four potency groups.

Allergens↗

Allometric principles for interspecies extrapolation in toxicological risk assessment--empirical investigations.

Four types of data (toxicokinetic data of pharmaceuticals from six species including humans, LD(50) values from eight animal species, long-term NOAEL values of pesticides from mice, rats, and dogs, and toxicity data on anti-neoplastic agents from six species including humans) were used for interspecies comparisons. Species differences with regard to kinetic parameters and toxicity were evaluated and the concordance with predictions by allometric scaling according to caloric demand (allometric exponent 0.75) or to body weight (allometric exponent 1) was checked. For LD(50) values, agreement was poor for both allometric concepts. Recently reported concordance of LD(50) species differences with body weight scaling could be traced back to biased data selection. The other three datasets are clearly in agreement with the allometric scaling according to caloric demand. Caloric demand scaling is thus proposed as a generic interspecies extrapolation method in the absence of substance-specific data. Moreover, the evaluated data make it possible to describe uncertainty associated with the process of interspecies extrapolation by allometric rules.

Animals↗