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Biomedical subjects

B Schmitz

Publications and source records attributed to B Schmitz.

At least 37 records · Page 2Linked to original sources

Visual field constriction in epilepsy patients treated with vigabatrin and other antiepileptic drugs: a prospective study.

BACKGROUND: Visual field constriction (VFC) has been described in about 30 % to 50 % of patients treated with the antiepileptic drug (AED) Vigabatrin (GVG). The exact incidence of VFC related to GVG exposure is unknown. Risk factors other than medication have not been identified as yet, and it is unclear whether the occurrence of VFC is restricted to the use of GVG. METHODS: In a longitudinal study, we investigated 60 epilepsy patients who received GVG and other AEDs. Patients underwent full ophthalmological examination including perimetry. RESULTS: 16 of 60 patients exposed to different AEDs developed VFC, which was judged as clinically relevant by an experienced neuroophthalmologist. VFC was observed significantly more often in patients treated with GVG as add-on- or monotherapy as compared with patients who had never been exposed to GVG (13/29 versus 3/31). Within the subgroup of 23 patients who received GVG as add-on therapy, those who developed VFC had been exposed to GVG for significantly longer than patients without VFC. The only non-treatment related feature associated with VFC was older age. Type and severity of epilepsy or type and number of concomitant AED were not related to the occurrence of VFC. CONCLUSIONS: The findings of an overrepresentation of VFC in patients receiving GVG and of a correlation between duration of GVG treatment and occurrence of VFC support the causal role of GVG treatment in the development of VFC. Old age is a possible risk factor for the development of VFC associated with GVG in epilepsy patients.

Adult↗

Snapping shrimp make flashing bubbles.

Snapping shrimp produce a loud crackling noise that is intense enough to disturb underwater communication. This sound originates from the violent collapse of a large cavitation bubble generated under the tensile forces of a high-velocity water jet formed when the shrimp's snapper-claw snaps shut (Fig. 1). Here we show that a short, intense flash of light is emitted as the bubble collapses, indicating that extreme pressures and temperatures of at least 5,000 K (ref. 4) must exist inside the bubble at the point of collapse. We have dubbed this phenomenon 'shrimpoluminescence' - the first observation, to our knowledge, of this mode of light production in any animal - because of its apparent similarity to sonoluminescence, the light emission from a bubble periodically driven by ultrasound.

Animals↗

[Propofol-remifentanil versus sevoflurane-remifentanil for anesthesia for pediatric procedures in infants, children and adolescents].

INTRODUCTION: The aim of this study was to compare total intravenous anaesthesia (TIVA) using propofol and remifentanil (P/R-group) and balanced anaesthesia (BA) using sevoflurane and remifentanil (S/R-group) for paediatric surgery. PATIENTS AND METHODS: A total of 120 patients aged 6 months to 16 years scheduled for elective minor lower abdominal surgery were randomly assigned to receive either propofol (5-10 mg/kg/h) and remifentanil (0.125-1.0 microgram/kg/min) or sevoflurane (1.0-1.5 MAC) and remifentanil (0.125-1.0 microgram/kg/min). Perioperative haemodynamics as well as recovery and discharge times, PONV and side-effects were studied. The patients vigilance, comfort and pain intensity were assessed postoperatively using the objective pain discomfort scale, the Steward post-anaesthetic recovery score and a visual analogue scale. RESULTS: Postoperative recovery (9.0 vs 11.6 min) and extubation times (11.8 vs. 15.0 min) as well as the time taken until a Steward post-anaesthetic recovery score > 3/4 (15.2 vs. 21.4 min) was reached were significantly shorter in the P/R-group. However, the length of time until discharge to the ward, postoperative comfort, pain intensity and analgesic requirements as well as PONV were comparable in both groups. CONCLUSIONS: With regards to the investigated parameters, TIVA with propofol and remifentanil is equally effective as BA with sevoflurane and remifentanil in paediatric patients. However, considering the selected dosing regimen, recovery times were significantly shorter for children after TIVA.

Abdomen↗

O-GlcNAc expression in developing and ageing mouse brain.

In order to understand whether there is a specific role for the posttranslational N-acetylglucosamine modification linked O-glycosidically (O-GlcNAc) to serine and threonine residues of proteins during development and/or ageing of the brain, we investigated the O-GlcNAc expression of early postnatal cerebellar neurons as well as of mouse brain of different ages. In all cells either in culture or of cryosections mainly the nuclei and nuclear membranes were stained with an O-GlcNAc specific monoclonal antibody. In cerebellar neurons in culture the level of expression could be manipulated by directly interfering with either the biosynthesis of GlcNAc or the removal of O-GlcNAc from proteins confirming the dynamic nature of this protein modification. O-GlcNAc was ubiquitously expressed in mouse brains from embryonic day 10 until late adulthood with some variations in expression strength from cell to cell. In addition, no significant difference in O-GlcNAc expression of subcellular fractions from brains of mice which age at an accelerated rate could be detected compared to normal mice. Taken together these observations support the view that the O-GlcNAc modification has important functional roles for physiological processes of neural cell throughout development, in adulthood and ageing.

Acetylgalactosamine↗

Overexpression of the adenovirus type 12 (Ad12) pTP or E1A gene facilitates Ad12 DNA replication in nonpermissive BHK21 hamster cells.

In the adenovirus type 12 (Ad12) hamster cell system, abortive virus infection is one of the factors associated with the highly efficient oncogenesis in newborn Syrian hamsters. We have shown earlier that the replication and efficient late transcription of the Ad12 genome are blocked in Syrian hamster cells. Some of the early Ad12 functions are transcribed in these cells, although at a minimal rate. In the present study, we demonstrate that low expression levels of the E1A and precursor to terminal protein (pTP) genes of Ad12 seem to be responsible for the lack of Ad12 DNA replication in hamster cells. The Ad12 genes for the E1A functions or for pTP were tethered to the strong early promoter of the human cytomegalovirus and transfected into BHK21 cells. Subsequently, these cells were infected with Ad12 virions. In Ad12-infected BHK21 cells, which overexpressed pTP or E1A, full-length Ad12 DNA was de novo synthesized, as documented by metabolic labeling with [3H]thymidine and by zone velocity sedimentation in alkaline sucrose gradients followed by gel electrophoresis of the 3H-labeled DNA and Southern blot hybridization to 32P-labeled Ad12 DNA. Transfection of the cloned E1A region of Ad2 yielded similar results. The newly synthesized Ad12 DNA was covalently linked to pTP. The Ad12 DNA binding protein (DBP) and DNA polymerase (pol) genes were transcribed at levels similar to those in merely Ad12-infected cells. In pTP or E1A gene-transfected and Ad12-infected BHK21 cells, marginal levels of late Ad12 mRNA were detectable. Late Ad12 proteins were, however, not synthesized. Apparently, Ad12 DNA replication in hamster cells is rendered impossible due to insufficient threshold levels of the viral E1A and/or pTP.

Adenovirus E1A Proteins↗

Encephalomyelitis due to Cryptococcus neoformans var gattii presenting as spinal tumour: case report and review of the literature.

A 24 year old immunocompetent German resident is described who developed multifocal encephalomyelitis due to infection with Cryptococcus neoformans var gatti, commonly considered a disease of tropical regions. In the light of current knowledge on the epidemiology of C neoformans var gatti and the travel history of the patient it is assumed that the infection was acquired outside Europe. As exclusive intramedullary involvement is an outstandingly rare manifestation in spinal cryptococcosis, the particular diagnostic procedure and the therapeutic strategies are discussed

Adult↗

Do rodent and human brains have different N-glycosylation patterns?

A large number of studies on the structure of N-glycosidically linked oligosaccharides from glycoproteins of different organs and/or different species have been carried out in the past using various combinations of techniques such as monosaccharide analysis, permethylation, peracteylation, exoglycosidase sequencing, normal and reversed phase HPLC, mass spectrometry and nuclear magnetic resonance spectroscopy. Although it is widely accepted that the processing of N-glycans in the ER and Golgi of mammalian cells follows the same principal metabolic rules, analyses have revealed that the glycosylation pattern of a particular protein may differ depending on the cell type in which it is expressed. N-glycans from brain glycoproteins have been shown to include a variety of hybrid- and complex-type structures with structural features that are not so commonly found on glycoproteins from other organs and which have, therefore, been classified as 'brain-specific'. Comparison of the N-glycans of glycoproteins from homogenates of rat, mouse and human brains confirm that, in general, glycoproteins from human brain show a similar profile of brain-specific N-glycans as glycoproteins from mouse and rat brain.

Animals↗

Signaling via water currents in behavioral interactions of snapping shrimp (Alpheus heterochaelis).

The snappping shrimp Alpheus heterochaelis produces a variety of different water currents during intraspecific encounters and interspecific interactions with small sympatric crabs (Eurypanopeus depressus). We studied the mechanisms of current production in tethered shrimp and the use of the different currents in freely behaving animals. The beating of the pleopods results in strong posteriorly directed currents. Although they reach rather far, these currents show no distinctions when directed toward different opponents. Gill currents are produced by movements of the scaphognathites (the exopodites of the second maxillae) and can then be deflected laterally by movements of the exopodites of the first and second maxillipeds. These frequent but slow lateral gill currents are most probably used to enhance chemical odor perception. The fast and focused, anteriorly directed gill currents, however, represent a powerful tool in intraspecific signaling, because they reach the chemo- and mechanosensory antennules of the opponent more often than any other currents and also because they are produced soon after previous contacts between the animals. They may carry chemical information about the social status of their producers since dominant shrimp release more anterior gill currents and more water jets than subordinate animals in intrasexual interactions.

Animals↗

[In vitro study of marginal quality of small approximal composite fillings].

The aim of the study was to compare different preparation methods and filling techniques for class II microcavities in vitro. The following methods were evaluated: Sonicsys halftorpedo, Sonicsys halfsphere, Sonicsys approx, Siplus, Piezo cavity system and rotating finishing bur. Every cavity type was obturated with a flowable (Tetric flow) and with a hybrid composite (Tetric ceram). One group consisted of prefabricated ceramic inlays (Sonicsys approx) and one group was filled with a three-site light curing technique. This resulted in 128 composite fillings. The evaluation of the quality of the margins under the SEM demonstrated a statistically significant higher percentage of perfect margins for Siplus compared with the PCS-System (88% versus 58% perfect margins). Marginal adaptation before and after thermocycling demonstrated the following results: Bewelled margins showed in general better adaptation than box-shaped cavities. Similar results were found for normal and flowable composites. Microcavities with occlusal access prepared with the sonicsys halfsphere showed in general better marginal adaptation in comparison to the other methods tested. It was concluded that simple obturation techniques can lead to a stable adaptation of the margins.

Composite Resins↗

How snapping shrimp snap: through cavitating bubbles.

The snapping shrimp (Alpheus heterochaelis) produces a loud snapping sound by an extremely rapid closure of its snapper claw. One of the effects of the snapping is to stun or kill prey animals. During the rapid snapper claw closure, a high-velocity water jet is emitted from the claw with a speed exceeding cavitation conditions. Hydrophone measurements in conjunction with time-controlled high-speed imaging of the claw closure demonstrate that the sound is emitted at the cavitation bubble collapse and not on claw closure. A model for the bubble dynamics based on a Rayleigh-Plesset-type equation quantitatively accounts for the time dependence of the bubble radius and for the emitted sound.

Air↗

Familial form of hirschsprung disease: nucleotide sequence studies reveal point mutations in the RET proto-oncogene in two of six families but not in other candidate genes.

Hirschsprung disease (HSCR; McKusick 142623) or aganglionic megacolon is a frequent (1 in 5,000 live births) heritable disorder of the enteric nervous system. By haplotyping with a variety of microsatellite markers, by amplifying all 20 exons of the RET proto-oncogene and by applying a direct DNA sequencing protocol, we have analyzed the DNA from HSCR patients in 6 different families. In one family with a joint occurrence of HSCR and FMTC (follicular medullary thyroid carcinoma), we have identified a mutation in codon 609 in one out of 6 cysteine residues encoded in exon 10 of the RET gene. This C609R point mutation has not previously been reported to cause HSCR. In 2 of the HSCR patients described here from different families, we have found a mutation in exon 2 (R77C) and a silent mutation in exon 3 (Y204Y), respectively, in the extracellular part of the RET proto-oncogene. In introns 2 and 17 of the RET proto-oncogene in 2 families, we have detected single nucleotide exchanges that are probably polymorphisms with unknown, if any, relations to HSCR. The DNA sequences of 5 further genes (GDNF, GDNFRalpha, EDN3, EDNRB, and NTN), that may contribute to the development of HSCR, have not shown mutations in the patients analyzed so far. In 2 of the reported families with several affected children and one grandchild, sequence analyses revealed no mutations in the coding regions of any of the candidate genes analyzed.

Adult↗

Methylation mosaicism of 5'-(CGG)(n)-3' repeats in fragile X, premutation and normal individuals.

Fragile X syndrome (FRAXA) is characterized at the molecular level by an expansion of a naturally occurring 5'-(CGG)(n)-3' repeat in the promoter and 5'-untranslated region (5'-UTR) of the fragile X mental retardation (FMR1) gene on human chromosome Xq27.3. When expanded, this region is usually hypermethylated. Inactivation of the FMR1 promoter and absence of the FMR1 protein are the likely cause of the syndrome. By using the bisulfite protocol of the genomic sequencing method, we have determined the methylation patterns in this region on single chromosomes of healthy individuals and of selected premutation carriers and FRAXA patients. In control experiments with unmethylated or M- Sss I-premethylated DNAs, this protocol has been ascertained to reliably detect all cytidines or 5-methylcytidines as unmethylated or methylated nucleotides, respectively. Analyses of the DNA from FRAXA patients reveal considerable variability in the lengths of the 5'-(CGG)(n)-3' repeats and in the levels of methylation in the repeat and the 5'-UTR. In one patient (OEl) with high repeat length hetero-geneity ( n = 15 to >200), shorter repeats (n = 20-80) were methylated or unmethylated, longer repeats ( n = 100-150) were often completely methylated, but one repeat with n = 160 proved to be completely unmethylated. This type of methylation mosaicism was observed in several FRAXA patients. In healthy females, methylated 5'-CG-3' sequences were found in some repeats and 5'-UTRs, as expected for the sequences from one of the X chromosomes. The natural FMR1 promoter is methylation sensitive, as demonstrated by the loss of activity in transfection experiments using the unmethylated or M- Sss I-premethylated FMR1 promoter fused to the luciferase gene as an activity indicator.

5' Untranslated Regions↗

The human 20-kDa 5'-(CGG)(n)-3'-binding protein is targeted to the nucleus and affects the activity of the FMR1 promoter.

Previous reports have described the human DNA CGG repeat-binding protein (CGGBP1 or p20), which binds specifically to nonmethylated, but not to methylated, 5'-(CGG)(n)-3' repeats in the promoter of the fragile X mental retardation 1 (FMR1) gene. The results of transfection experiments into human HeLa cells using a p20-green fluorescent protein fusion construct indicate that the p20 protein is targeted to the nucleus. By deletion analyses, a nuclear localization signal has been found between amino acids 80 and 84. Deletions between amino acids 69 and 71 and between 95 and 167 interfere with 5'-(CGG)(n)-3' binding. The results of electrophoretic mobility shift assays using DNA with 5'-(CGG)(n)-3' repeats of different lengths render it likely that oligomers of the p20 protein bind to the repeat. In cotransfection experiments, the activity of the FMR1 promoter is reduced by the presence of p20. Upon transfection of the p20 cDNA construct into HeLa cells, transcription of the endogenous FMR1 gene is decreased. The green fluorescent protein-p20 fusion protein associates preferentially with the telomeres of the short arms of human chromosomes 13, 14, 15, 21, and 22. Their telomeres carry the genes for the 28 S rRNA, which contain 5'-(CGG)(n)-3' repeats. The translated region of the p20 gene from three healthy, five fragile X syndrome, and five premutation-carrying individuals has been sequenced, but mutations have not been detected.

Amino Acid Sequence↗

Decapod crustacean chelipeds: an overview.

The structure, growth, differentiation and function of crustacean chelipeds are reviewed. In many decapod crustaceans growth of chelae is isometric with allometry level reaching unity till the puberty moult. Afterwards the same trend continues in females, while in males there is a marked spurt in the level of allometry accompanied by a sudden increase in the relative size of chelae. Subsequently they are differentiated morphologically into crusher and cutter making them heterochelous and sexually dimorphic. Of the two, the major chela is used during agonistic encounters while the minor is used for prey capture and grooming. Various biotic and abiotic factors exert a negative effect on cheliped growth. The dimorphic growth pattern of chelae can be adversely affected by factors such as parasitic infection and substrate conditions. Display patterns of chelipeds have an important role in agonistic and aggressive interactions. Of the five pairs of pereiopods, the chelae are versatile organs of offence and defence which also make them the most vulnerable for autotomy. Regeneration of the autotomized chelipeds imposes an additional energy demand called "regeneration load" on the incumbent, altering energy allocation for somatic and/or reproductive processes. Partial withdrawal of chelae leading to incomplete exuviation is reported for the first time in the laboratory and field in Macrobrachium species.

Agonistic Behavior↗

Selectins (CD62L, CD62P) and megakaryocytic glycoproteins (CD41a, CD42b) mediate megakaryocyte-fibroblast interactions in human bone marrow.

Previous in vitro studies are in keeping with the finding that isolated and enriched megakaryocytes attach to bone marrow fibroblasts and generate an increased growth of these cells. This process was assumed to depend on a close spatial relationship between both cell types which supports the paracrine effect of platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-beta1. Moreover, adhesion molecules including beta1 integrin receptors and fucosylated structures were determined to play an important role in these complex interactions. However, up to now the influence of megakaryocyte expressed glycoproteins CD41a and CD42b in these processes was not investigated. In addition, the role of megakaryocytic CD62P and also of CD62L, both adhesion molecules of the selectin group, could also be of interest. Following isolation and enrichment of bone marrow megakaryocytes and fibroblasts, both cell populations were characterized regarding their expression of these factors by applying immunocytochemical techniques. Additionally, their influence on adhesion of megakaryocytes to fibroblasts as well as fibroblast growth was evaluated by comparative megakaryocyte-fibroblast co-cultures and inhibition studies using specific monoclonal antibodies (mabs). Fibroblast monocultures served as controls. In these experiments, selectin-specific antibodies significantly reduced megakaryocyte attachment to fibroblast feeder layers and fibroblast growth in the co-cultures. The effect of CD41a and CD42b specific antibodies was limited to megakaryocyte-dependent fibroblast growth. These results elucidate the involvement of the selectins CD62P and CD62L in the basal activation of megakaryocytes inducing their attachment to bone marrow fibroblasts. In contrast, the megakaryocyte glycoproteins CD41a and CD42b exert their effect on the megakaryocyte dependent fibroblast growth. Altogether, it is tempting to speculate that the various interactions of these mediators reflect certain steps in the complex pathomechanisms causing the evolution of (reactive) myelofibrosis in hematopoietic neoplasias accompanied by megakaryocytic proliferation.

Bone Marrow↗

The frequency and correlates of dyspnea in patients with advanced cancer.

Dyspnea is a devastating symptom in patients with advanced cancer. Unfortunately, very limited research has been done on the frequency and correlates of dyspnea in this particular patient population. The purpose of this prospective study was to assess the frequency of moderate to severe dyspnea and the correlates of dyspnea in a population of ambulatory terminally ill cancer patients. One hundred thirty-five consecutive patients attending a multidisciplinary pain clinic were tested for respiratory function (vital capacity, peak flow, maximal inspiratory pressure, and oxygen saturation). All patients gave their rating of dyspnea, anxiety, and fatigue/tiredness using visual analogue scales (VAS). Lung involvement by the tumor (primary or metastatic) was determined from the patient's chart. Moderate dyspnea occurred in 74/135 (55%) patients with terminal cancer. Lung involvement (r = 0.285, P = 0. 0009), anxiety (r = 0.306, P = 0.0003), fatigue/tiredness (r = 0.211, P = 0.0146), and vital capacity (r = -0.189, P = 0.0444) were significantly correlated with the intensity of dyspnea. Multivariate analysis demonstrated that lung involvement (P = 0.0016) and anxiety (P = 0.0027) were independently correlated with the intensity of dyspnea. In the subgroup of patients with moderate to severe dyspnea, multivariate analysis found anxiety (P = 0.0318) and maximal inspiratory pressure (P = 0.0187) to be independent correlates of the intensity of dyspnea. Dyspnea is a frequent symptom in patients with advanced cancer. The presence of cancer in the lungs, anxiety, and maximal inspiratory pressure are correlates of the intensity of dyspnea in this patient population. Possible treatments addressing low maximal inspiratory pressure and anxiety are needed, as well as further research in finding new correlates of dyspnea in advanced cancer patients.

Aged↗

Interferon alpha2b directly induces fibroblast proliferation and transforming growth factor beta secretion of macrophages.

To elucidate the effects of interferon alpha2b (IFN-alpha) on normal human bone marrow, fibroblasts from patients without haematopoietic pathology were cultivated and used in stimulation experiments. Further, co-cultures with highly enriched fractions of megakaryocytes and bone marrow macrophages were analysed. In this context, the influence of cell-to-cell interactions and humoral factors was determined in transwell and neutralization studies. Finally, secretion of platelet-derived growth factor (PDGF) and transforming growth factor beta1 (TGF-beta1) by single megakaryocytes and macrophages was examined by using the reverse haemolytic plaque assay (RHPA). Following these experimental designs, a direct proliferative activity of IFN-alpha on bone marrow fibroblasts could be demonstrated. In the unstimulated co-cultures, the megakaryocyte- but not the macrophage-enriched fraction induced fibroblast growth and [3H]-thymidine uptake. This effect was dependent on cell-to-cell contact and also on the influence of TGF-beta and PDGF. In the megakaryocyte-enriched co-cultures, the fibroblast proliferation was not altered by IFN-alpha, but in the macrophage fibroblast cultures addition of IFN-alpha enhanced fibroblast growth and [3H]-thymidine uptake was distinctively higher than in the monocultures. This effect was not obvious in the transwell or neutralization experiments. Finally, IFN-alpha treatment exerted a significantly elevated TGF-beta1 secretion in single macrophages. Our findings are in keeping with the assumption that several pathomechanisms participate in IFN-alpha-induced myelofibrosis, including direct and indirect effects.

Adult↗