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R Schnabel

Publications and source records attributed to R Schnabel.

At least 73 records · Page 4Linked to original sources
PubMed1996

Cell autonomous expression of perlecan and plasticity of cell shape in embryonic muscle of Caenorhabditis elegans.

Perlecan, a component of the extracellular matrix (ECM), is essential for myofilament formation and muscle attachment in Caenorhabditis elegans. We show here that perlecan is a product of muscle and that it behaves in a cell autonomous fashion. That is, perlecan expressed in an individual muscle cell does not spread beyond the borders of the ECM underlying that cell. Using a polyclonal antibody that recognizes all isoforms of perlecan, we demonstrate that this protein first appears extracellularly at the comma stage (approx. 350 min) of development. We also show that during morphogenesis muscle cells have a heretofore undescribed plasticity of shape. This ability to regulate cell shape allows cells within a muscle quadrant to compensate for missing cells and to form a functional quadrant. A dramatic example of this morphological flexibility can be observed in animals in which the D blastomere has been removed by laser ablation. Such animals, lacking 20 of the 81 embryonic body wall muscle cells, can survive to become viable adult animals indistinguishable from wildtype animals. This demonstrates that the assembly of an embryo via a stereotypic lineage does not preclude a more general regulation during morphogenesis. It appears that embryos are flexible enough to immediately compensate for drastic alterations in tissue composition, a feature of development that may be of general importance during evolution.

Animals↗
PubMed1996

mex-1 and the general partitioning of cell fate in the early C. elegans embryo.

It is thought that at least some of the initial specification of the five somatic founder cells of the C. elegans embryo occurs cell-autonomously through the segregation of factors during cell divisions. It has been suggested that in embryos from mothers homozygous for mutations in the maternal-effect gene mex-1, four blastomeres of the 8-cell embryo adopt the fate of the MS blastomere. It was proposed that mex-1 functions to localise or regulate factors that determine the fate of this blastomere. Here, a detailed cell lineage analysis of 9 mex-1 mutants reveals that the fates of all somatic founder cells are affected by mutations in this gene. We propose that mex-1, like the par genes, is involved in establishing the initial polarity of the embryo.

Alleles↗
PubMed1996

Relationship between ischemic damage and concentrations of phenytoin and phenobarbital in the brain cortex of epileptic patients in vegetative state at death.

Post-mortem concentrations of phenytoin (PHT) and phenobarbital (PB) were determined by high-performance liquid chromatography in the cortical matter of specified brain regions and in the serum (total and free) from 3 epileptic males in vegetative state and compared to the data of 45 deceased epileptic control patients. The duration of the vegetative state was 12 days, 15 days or about 4 months until death and was associated with corresponding stages of generalized ischemic brain damage. The histological examination was completed by immunohistochemical and morphometric methods. According to other investigators nerve cells are the major binding sites for PHT and PB in the cerebral cortex of rodents. But, in the 3 comatose patients the PHT and PB concentrations of the isocortex and neocerebellum were not significantly decreased in comparison with the control patients despite necrosis and loss of neurons as well as other distinct tissue alterations. The results strongly favor the non-specific binding of PHT and PB to cells and subcellular structures of the brain-mainly based on simple physico-chemical principles.

Adult↗
PubMed1996

[Extracorporeal shockwave lithotripsy (SWL) of common bile duct calculi without previous endoscopic papillotomy].

In 17 patients (8 men, 9 women; mean age 61.5 years) with problematic bile-duct stones (papilla endoscopically inaccessible, residual bile-duct stones after recent laparoscopic cholecystectomy or age below 25 years) the chances of successful treatment by ESWL without sphincterotomy were examined. In 15 patients with solitary stones measuring up to 14 mm "pulverization-ESWL" produced complete freedom from stones after spontaneous migration of fragments through the intact papilla. Only two patients with two ductal stones measuring up to 15 mm still had residual fragments in the bile duct after treatment. The ideal stone for ESWL without sphincterotomy is thus the solitary bile-duct stone measuring up to 14 mm. Before performing a high-risk sphincterotomy, before re-operation and in young patients one should therefore always examine whether ESWL without sphincterotomy is indicated.

Adolescent↗
PubMed1995

Apolipoprotein E genotype and neuropathological phenotype in two members of a German family with chromosome 14-linked early onset Alzheimer's disease.

Molecular genetic analysis was performed in two autopsy-confirmed cases of early-onset Alzheimer's disease belonging to a large German pedigree [FAD2, according to the nomenclature of St. George-Hyslop, et al. (1987) Science 235:885-890]. The disease in this family has been linked to chromosome 14. As gene interactions are considered to influence the age of onset and tissue pathology in Alzheimer's disease, we have studied three candidate genes that could modify disease progression. In this study a new polymerase chain reaction (PCR) assay was established for apolipoprotein E genotyping in archival neuropathological tissue, exon 17 of the amyloid precursor protein gene was directly sequenced, and a candidate mutation site at nucleotide (nt) 5460 of the mitochondrial NADH dehydrogenase subunit gene ND2 was analyzed employing PCR followed by HphI digestion. Whereas no sequence variations were detected in exon 17APP or at nt5460 of mitochondrial DNA, the apolipoprotein E genotypes of the two cases differed. Neuropathological examination revealed a higher number of beta A4-positive amyloid plaques and a larger total tissue area covered by beta A4 deposits in the epsilon 3/epsilon 3 homozygote. In contrast, the number of cortical neurofibrillary tangles and the number of plaques with tau-positive neurites appeared to be higher in the epsilon 3/epsilon 4 heterozygote. Our findings support the view that the chromosome 14 genetic defect, rather than apolipoprotein E genotype, is the preeminent factor determining Alzheimer's disease pathology in this family.

Alzheimer Disease↗
PubMed1995

Lack of effect of histological lesions on the phenytoin and phenobarbital concentrations in the brain cortex of epileptic patients.

Postmortem concentrations of phenytoin (PHT) and phenobarbital (PB) were determined in 24 specimens of the frontal, temporal, occipital or neocerebellar cortex with different pathological changes and in the serum (total and free) from 11 epileptic patients. The cortical lesions were characterized by various degrees of neuronal loss or necrosis associated with other changes such as proliferated gliocytes, fibre gliosis, Rosenthal fibres or numerous corpora amylacea. According to other investigators neurons are the main binding sites of PHT and PB in rodent brains. The PHT and PB concentrations in 20 cortical lesions from nine patients were not significantly reduced as compared to the data of 46 deceased epileptic control patients. A significantly decreased PB value could only be demonstrated in the temporal specimen of an old scarred infarction with complete demyelination. On the other hand a slight but significant increase of PB was observed in three neocortical samples from a child exhibiting severe brain oedema and thrombosis of the sinuses. The results favour the unspecific binding of PHT and PB to cerebral tissue constituents and do not support the hypothesis of major binding to specific receptors.

Aged↗
PubMed1995

Establishment of left-right asymmetry in the Caenorhabditis elegans embryo: a multistep process involving a series of inductive events.

Bilateral pairs of blastomeres derived from the founder cell AB, the anterior blastomere of the 2-cell stage, in the Caenorhabditis elegans embryo are initially equivalent in their developmental potential. Recently, we showed that an induction at the 12-cell stage by a blastomere called MS is necessary to establish the differences between left and right pairs of blastomeres in the anterior part of the embryo. Further analysis of the process of creating left-right asymmetry reveals that the induction at the 12-cell stage is only the first of a series of inductions establishing the left-right asymmetry of the embryo. We describe here two further inductions that create additional asymmetries in the posterior part of the embryo. One induction occurs at the 24-cell stage among AB descendants themselves. This induction is restricted to the left side of the embryo as a consequence of the fate changes induced by MS at the 12-cell stage. The second induction requires again blastomeres of the MS lineage and also occurs around the 24-cell stage. Together these inductions establish the fate differences observed in the development of left-right pairs of blastomeres in the embryo.

Animals↗
PubMed1995

Specification of anterior-posterior differences within the AB lineage in the C. elegans embryo: a polarising induction.

In a C. elegans embryo the third cleavages of descendants of the anterior blastomere AB of the 2-cell stage create pairs of blastomeres that develop differently. By laser ablation experiments we show that the fates of all the posterior daughters of this division depend on an induction occurring three cleavages before these blastomeres are born. The time of induction precludes a direct effect on cell fate. Alternatively, we suggest that the induction creates a heritable cell polarity which is propagated through several divisions. We suggest a model to demonstrate how a signal could be propagated through several rounds of cell division. An important implication of our observations is that this early induction acts to specify blastomere identity, not tissue type. A detailed lineage analysis revealed that altering the inductive signal alters complex lineage patterns as a whole. The induction described here, together with two inductions described previously can be used to illustrate how the anterior portion of the C. elegans embryo can be successively subdivided into blastomeres with unique developmental potential.

Animals↗
PubMed1995

Duels without obvious sense: counteracting inductions involved in body wall muscle development in the Caenorhabditis elegans embryo.

During the first four cleavage rounds of the Caenorhabditis elegans embryo, five somatic founder cells AB, MS, E, C and D are born, which later form the tissues of the embryo. The classical criterion for a cell-autonomous specification of a tissue is the capability of primordial cells to produce this tissue in isolation from the remainder of the embryo. By this criterion, the somatic founder cells MS, C and D develop cell-autonomously. Laser ablation experiments, however, reveal that within the embryonic context these blastomeres form a network of duelling cellular interactions. During normal development, the blastomere D inhibits muscle specification in the MS and the C lineage inhibits muscle specification in the D lineage. These inhibitory interactions are counteracted by two activating inductions. As described before the inhibition of body wall muscle in MS is counteracted by an activating signal from the ABa lineage. Body wall muscle in the D lineage is induced by MS descendants, which suppress an inhibitory activity of the C lineage. The interaction between the D and the MS lineage occurs through the C lineage. An interesting feature of these cell-cell interactions is that they do not serve to discriminate between equivalent cells but are permissive or nonpermissive inductions. No evidence was found that the C-derived body wall muscle also depends on an induction, which suggests that possibly three different pathways coexist in the early embryo to specify body wall muscle, two of which are, in different ways, influenced by cell-cell interactions and a third that is autonomous. This work supplies evidence that cells may acquire transient states during embryogenesis that influence the specification of other cells in the embryo. These states, however, may not be reflected in the developmental potentials of the cells themselves. They can only be scored indirectly by their action on the specification of other cells in the embryo. Blastomeres that behave cell-autonomously in isolation are nevertheless subjected to cell-cell interactions in the embryonic context. Why this should be is an intriguing question. The classical notion has been that blastomeres are specified autonomously in nematodes. In recent years, it was established that at least five inductions are required to determine the AB descendants of C. elegans, whereas the P1 descendants have been typically viewed to develop more autonomously. It appears now that inductions also play a major role during the determination of P1-derived blastomeres.

Animals↗
PubMed1995

[Diagnosis and therapy of primary malignant fibrous histiocytoma of the kidney].

Malignant Fibrous Histiocytoma (MFH) is an unfrequent mesenchymal tumor first described by O'Brian in 1964 [1, 16]. The most common site of this malignancy is the limbs area and the retroperitoneum. Primary involvement of the kidney is extremely rare. Only thirteen cases are well documented in the literature. We report an additional case of such primary renal tumor.

Aged↗
PubMed1994

Autonomy and nonautonomy in cell fate specification of muscle in the Caenorhabditis elegans embryo: a reciprocal induction.

EMS, a blastomere of the Caenorhabditis elegans embryo, produces body wall muscle cell-autonomously in isolation. Within the embryonic context, however, the specification of body wall muscle derived from EMS depends on inductive interactions between its daughter MS and ABa descendants that are required to overcome inhibitory interactions with other cells. The inductive events between the MS and ABa descendants are reciprocal, specifying subsequent fates in both lineages. Both induction events are blocked by mutations in the gene glp-1, known to encode a Notch-like transmembrane receptor protein.

Animals↗
PubMed1994

Ultrastructural studies of acute rejection following single lung transplantation in the rat--histological and immunohistological findings.

Nowadays the acute and especially chronic lung rejection are the major problems after lung transplantation (L-Tx) with relevant influence on longterm survival. We performed lung transplantation in rats to study a possible role of ultrastructural lesions in the graft during the acute rejection process, concerning their reversibility/irreversibility and influence of the chronic rejection. Based on histologic and immunohistologic studies after L-Tx in MHC-different and strong reactive rat strain combination AVN-LEW and filial generation (AVN-LEW)F1-LEW (n = 57 and n = 32) electronmicroscopic studies (TEM, SEM) were performed in the combination AVN-LW (n = 20) on postoperative day 0, 1, 2 and 5, all without immunsuppressive therapy. Syngenic grafts (LEW-LEW; n = 12) served as controls. Histologically the allografts were classed according to the proven acute rejection phases latent, vascular, alveolar and destructive. The immunhistological and electronmicroscopic results correlated with these rejection phases. There was no difference between the rat strain combinations. All allografts developed acute rejection on postoperative day 2 and were destroyed on postoperative day 5/6. Initially T-helper-cells, later cytotoxic-T-cells and macrophages played the predominent role in the acute rejection process. In the ultrastructural specimens alterations of the blood vessels, pneumocytes type-II, and surfactant gave more information. Initially flattening of endothelial cells and circumscribed lesions of graft vessels occur, increasing in the allografts up to extensive vascular wall destructions, accompanied by total thrombotic occlusion. Disturbances of surfactant production observed in the grafts of all strain combinations are not homogenous.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Concentrations of carbamazepine and carbamazepine-10, 11-epoxide in serum, brain tumors and paratumorous cortex: a prospective study of 37 neurosurgically treated epileptic patients.

Concentrations of carbamazepine (CBZ) and its metabolite carbamazepine-10, 11-epoxide (CE) were determined in serum (free and total), brain tumors and paratumorous cortex from 37 epileptic patients. Tumor biopsies were available from 25 different gliomas, 5 hamartomas and 1 angioma. The free serum concentrations of CBZ and CE were highly correlated with the corresponding paratumorous concentrations (r = 0.94 and r = 0.93) and to a lower extent with the tumorous concentrations (r = 0.78 and r = 0.75). For CBZ the concentration ratios paratumorous cortex/serum free and tumor/serum free showed no significant differences between CBZ-resistant and -nonresistant patients. Apart from histological grade a significant influence of type and site of the tumors on their CBZ and CE concentration was not recognizable. The results indicate that resistance to CBZ therapy cannot be sufficiently explained by decreased paratumorous or tumorous levels of CBZ and CE.

Adolescent↗
PubMed1994

Genesis of an organ: molecular analysis of the pha-1 gene.

The organisation of organ formation is still an unsolved problem. Mutations in the zygotic lethal gene pha-1 affect a late step during organ development in the nematode C. elegans. In mutant embryos all tissues in the pharynx fail to undergo terminal differentiation and morphogenesis. The expression of an early differentiation marker in pharyngeal muscle precursors is not impaired in mutant embryos, which suggests that pharynx cells still acquire their identity. Therefore the gene defines an organ-specific terminal differentiation function. We cloned and sequenced the pha-1 gene and found that the deduced protein sequence contains features characteristic of the bZIP family of transcription factors. During embryogenesis a transgenic pha-1 reporter construct is expressed transiently in all pharynx precursor cells at the time when these cells become restricted to form the pharynx organ. A mosaic analysis of the requirement of pha-1 activity during pharynx formation is consistent with the notion that pha-1 acts cell-autonomously in all cells of the pharynx primordium. The data suggest that pha-1 initiates and coordinates programs required for cytodifferentiation and morphogenesis in all cell types of the entire organ on the transcriptional level. We propose that organs are independent developmental units whose identity is reflected on the gene regulatory level.

Amino Acid Sequence↗