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Biomedical subjects

R Schuh

Publications and source records attributed to R Schuh.

At least 19 recordsLinked to original sources

[Long-term results of surgical therapy of epicondylitis humeri radialis using the technique described by Mittelmeier].

INTRODUCTION: Tennis elbow is one of the most common stress induced pathological findings in patients consulting an orthopaedic surgeon. In refractory cases operation is indicated after conservative treatment. Several operative techniques have been published. We prefer the technique described by Mittelmeier. Aim of this study is to show long- term results of operative therapy of the tennis elbow using this technique. PATIENTS AND METHOD: Between 1.1.1980 and 31.12.1992 we performed 115 outpatient operations for epicondylitis humeri radialis using the technique described by Mittelmeier. After a mean follow-up of 15,3 years we could examine 98 patients according to the score of Roles and Maudsley. RESULTS: We found excellent results in 47 %, good results in 43 % and fair results in 10 % of the evaluated cases. All patients had a benefit concerning the operation. There was one infection as a serious complication which led to revision. CONCLUSION: In epicondylitis humeri radialis surgical therapy according to Mittelmeier leads to good long-term results and can be recommended for persistent radial epicondylitis.

Adult↗

[Experiences with 925 outpatient operations of carpal tunnel syndrome].

In the era of cost containment in our health care system the demand is made of increasing outpatient surgery e. g. for carpal tunnel syndrome. To show the possibilities of carpal tunnel release performed under outpatient conditions we analysed 925 consecutive cases during 1. 1. 1981 to 30. 4. 2001. A tourniquet was used in all cases. In 814 cases we used axillary plexus anaesthesia. 107 surgical interventions were done under local anesthesia. Two of these patients could not tolerate the tourniquet. Analgesia was complete in all but two cases. In two cases revision due to after bleeding was necessary. There were no further complications seen. The mean time for return to work was 21.3 days (min: 14, max: 36 days). The mean follow-up for these patients was 36 months. Numbness and paresthesias were relieved in 98 %, pain was relieved in 90 %, motoric weakness was relieved in 95 % of the hands. The overall satisfaction rate was 94 %. Carpal tunnel release can be performed safely and unexpensively under outpatient conditions.

Adolescent↗

Single mesodermal cells guide outgrowth of ectodermal tubular structures in Drosophila.

The Drosophila tracheal system, a tubular network, is formed from isolated ectodermal metameres by guided branch outgrowth and branch fusion. Branch outgrowth is triggered by the localized and transient activity of Branchless (Bnl/dFGF). Here, we report the discovery of a mesodermal cell that links the leading cells of outgrowing main branches 2.5 hr before they fuse. This bridge-cell serves as an essential guidance post and needs Hunchback (Hb) activity to exert its function. The bridge-cell provides cues acting in concert with Bnl/dFGF signaling to mediate directed branch outgrowth that ultimately leads to position-specific branch fusion.

Animals↗

Enantiomeric resolution of galanthamine and related drugs used in anti-Alzheimer therapy by means of capillary zone electrophoresis employing derivatized cyclodextrin selectors.

An analytical assay is presented for the determination of the enantiomeric composition of galanthamine and related synthetic and natural compounds. (-)-Galanthamine is isolated from Galanthus nivalis and is used in this optical pure form in the therapy of Alzheimer's disease. Recent efforts for a total synthesis of unichiral (-)-galanthamine is connected with the need for a fast and reliable assay for the determination of the optical purity of the end product, as well as for optimizing and controlling the final steps in total synthesis particularly the asymmetric transformation of narwedine. In this paper the enantiomeric resolution of these compounds is reported employing a capillary electrophoretic system with beta-cyclodextrin derived chiral selectors. With the proposed system a number of galanthamine and narwedine derived analogous compounds could be separated, including 1-bromo- and N-alkyl-substituted compounds.

Alzheimer Disease↗

A transcription unit at the ken and barbie gene locus encodes a novel Drosophila zinc finger protein.

We describe a novel Drosophila transcription unit, located in chromosome region 60A. It encodes a zinc finger protein that is expressed in distinct spatial and temporal patterns during embryogenesis. Its initial expression occurs in a stripe at the anterior and the posterior trunk boundary, respectively. The two stripes are activated and spatially controlled by gap-gene activities. The P-element of the enhancer trap line l(2)02970 is inserted in the 5'-region of the transcript and causes a ken and barbie (ken) phenotype, associated with malformation of male genital structures.

Amino Acid Sequence↗

The transcription factors KNIRPS and KNIRPS RELATED control cell migration and branch morphogenesis during Drosophila tracheal development.

Cell migration during embryonic tracheal system development in Drosophila requires DPP and EGF signaling to generate the archetypal branching pattern. We show that two genes encoding the transcription factors KNIRPS and KNIRPS RELATED possess multiple and redundant functions during tracheal development. knirps/knirps related activity is necessary to mediate DPP signaling which is required for tracheal cell migration and formation of the dorsal and ventral branches. Ectopic knirps or knirps related expression in lateral tracheal cells respecifies their anteroposterior to a dorsoventral migration behavior, similar to that observed in the case of ectopic DPP expression. In dorsal tracheal cells knirps/knirps related activity represses the transcription factor SPALT; this repression is essential for secondary and terminal branch formation. However, in cells of the dorsal trunk, spalt expression is required for normal anteroposterior cell migration and morphogenesis. spalt expression is maintained by the EGF receptor pathway and, hence, some of the opposing activities of the EGF and DPP signaling pathways are mediated by spalt and knirps/knirps related. Furthermore, we provide evidence that the border between cells acquiring dorsal branch and dorsal trunk identity is established by the direct interaction of KNIRPS with a spalt cis-regulatory element.

Animals↗

The tracheae defective gene encodes a bZIP protein that controls tracheal cell movement during Drosophila embryogenesis.

The tracheae defective (tdf) gene is required for the formation of the tracheal system during Drosophila embryogenesis. It encodes a putative bZIP transcription factor (TDF). Antibodies directed against TDF detect a nuclear protein in all tracheal cells before invagination and throughout tracheal system morphogenesis. Examination of tdf mutants revealed that tdf activity is not necessary for determining tracheal cell identity but for subsequent morphogenetic cell movements. tdf activity is under the control of trachealess, the key regulator gene for tracheal development. In contrast, tdf activity is not dependent on and does not interfere with the fibroblast growth factor- (FGF) and Decapentaplegic- (DPP) mediated signalling that direct guided tracheal cell migration. Our results suggest that lack of tdf activity affects tracheal cell migration in general rather than specific aspects of cell migration. tdf activity involves a maternal and zygotic component and its requirement is not limited to tracheal system formation. The complex spatiotemporal patterns of TDF expression in the embryo correspond to defects, suggesting that cell migration is impaired. We propose that the bZIP protein TDF functions as a co-regulator of target genes that provide cells with the ability to migrate.

Amino Acid Sequence↗

Regulation of Drosophila spalt gene expression.

The region-specific homeotic gene spalt is involved in the specification of terminal versus trunk structures during early Drosophila embryogenesis. Later in development spalt activity participates in specific processes during organogenesis and larval imaginal disc development. The multiple functions of spalt are reflected in distinct spatio-temporal expression patterns throughout development. Here we show that spalt cis-regulatory sequences for region-specific and organ-specific expression are clustered. Their organization may provide the structural basis for the diversification of expression pattern within the spalt/spalt related/spalt adjacent gene complex. We also examined the transacting factor requirement for the blastodermal spalt expression domains. They are under the genetic control of maternal and gap gene products and we show that these products are able to bind to corresponding spalt cis-acting sequences in vitro. The results suggest that the transacting factors, as defined by genetic studies, functionally interact with the spalt regulatory region. In addition, we provide evidence that a zygotic gene product of the terminal system, Tailless, cooperates with the maternal gene product Caudal and thereby activates gene expression in the terminal region of the embryo.

Animals↗

DPP controls tracheal cell migration along the dorsoventral body axis of the Drosophila embryo.

We report that DPP signaling is required for directed tracheal cell migration during Drosophila embryogenesis. The failure of tracheal cells to receive the DPP signal from adjacent dorsal and ventral cells results in the absence of dorsal and ventral migrations. Ectopic DPP signaling can reprogram cells in the center of the placode to adopt a dorsoventral migration behavior. The effects observed in response to ectopic DPP signaling are also observed upon the tracheal-specific expression of a constitutive active DPP type I receptor (TKV(Q253D)), indicating that the DPP signal is received and transmitted in tracheal cells to control their migration behavior. DPP signaling determines localized gene expression patterns in the developing tracheal placode, and is also required for the dorsal expression of the recently identified BRANCHLESS (BNL) guidance molecule, the ligand of the BREATHLESS (BTL) receptor. Thus, DPP plays a dual role during tracheal cell migration. It is required to control the dorsal expression of the BNL ligand; in addition, the DPP signal recruits groups of dorsal and ventral tracheal cells and programs them to migrate in dorsal and ventral directions.

Activin Receptors↗

Isolation, characterization, and organ-specific expression of two novel human zinc finger genes related to the Drosophila gene spalt.

The region-specific homeotic gene spalt (sal) of Drosophila specifies head and tail as opposed to trunk segments. During later stages of ontogenesis, sal is also expressed and required in a small number of tissues and organs in the developing embryo. sal encodes a zinc finger protein of unusual but characteristic structure. We made use of these unique features to isolate sal-like genes from humans. Here we report the isolation and molecular characterization of two sal-like transcription units, termed Hsal1 and Hsal2, which are located on chromosomes 16q12.1 and 14q11.1-q12.1, respectively. Their transcripts are expressed in a limited number of adult organs, including the brain. While Hsal2 is evenly expressed in different brain areas, Hsal1 transcripts preferentially accumulate in the corpus callosum and the substantia nigra. In the fetal brain, transcripts of both genes were detected in neurons. The arrangement of sal-like zinc finger domains and their high degree of sequence similarity suggest a novel and conserved subfamily of human zinc finger transcription factors that is closely related to the Drosophila gene product encoded by the gene sal.

Adult↗

Regulation, function and potential origin of the Drosophila gene spalt adjacent, which encodes a secreted protein expressed in the early embryo.

During early embryogenesis of Drosophila the spatial and temporal expression patterns of the region-specific homeotic gene spalt (sal) and the neighbouring gene spalt adjacent (sala) extensively overlap. We show that the initial expression patterns of the two genes in the blastoderm also have identical genetic controls. However, while sal encodes a transcription factor, sala encodes a precursor protein from which a functional signal peptide is cleaved off to generate the secreted sala protein. Ectopic expression or absence of sala protein does not affect embryonic development, adult viability or fertility. In addition to sal and sala, we identified a third gene nearby, termed spalt related (salr), which shares coding sequence similarity and a late embryonic expression pattern with sal, but lacks the early expression domains that are shared by sal and sala. These results suggest that the three genes and their present cis-regulatory regions arose through a chromosomal rearrangement involving local duplication and transposition events in the 32F/33A region on the left arm of the second chromosome.

Amino Acid Sequence↗

Xenopus Xsal-1, a vertebrate homolog of the region specific homeotic gene spalt of Drosophila.

We have isolated an amphibian homolog of the homeotic gene spalt of Drosophila. Like its Drosophila counterpart the Xenopus Xsal-1 gene encodes a protein that contains three widely separated sets of sequence related double zinc finger motifs of the CC/HH-type as well as a single CC/HH zinc finger. The Xenopus gene encodes a fourth double zinc finger and a single CC/HC zinc finger motif that have no counterpart in the fly protein. Alternative splicing of Xsal-1 transcripts gives rise to RNAs coding for either four, three or two double zinc fingers, respectively. The main expression domains of Xsal-1 in early development are confined to distinct regions along the lateral axon tracts within the midbrain, hindbrain, and spinal cord. Outside the central nervous system Xsal-1 is expressed in the facio-acoustic ganglion and in the developing limb buds. The pattern of expression suggests that Xsal-1 might be under control of signals emanating from the notochord and/or the floor plate and that it might function in neuronal cell specification.

Alternative Splicing↗

Dual function of the region-specific homeotic gene spalt during Drosophila tracheal system development.

We report that the region-specific homeotic gene spalt affects the Drosophila tracheal system at two different stages of embryonic development. Both lack-of-function and gain-of-function experiments show that blastodermal spalt activity restricts tracheal development to 10 bilaterally positioned pairs of tracheal placodes in the trunk region by repressing placode formation in parasegments 2, 3 and 14. The results suggest that the activity of the zinc-finger type transcription factor encoded by spalt suppresses the molecular pathway that establishes tracheal development. spalt function is also necessary for the directed migration of the dorsal trunk cells, a distinct subset of tracheal cells. This process is a prerequisite for the formation of the dorsal trunk generated by fusion of adjacent tracheal metameres into a common tubular structure. The directed cell migration, in which spalt gene function participates, seems to be independent of branch fusion and general tracheal cell migration processes.

Animals↗

Suppression of normal and neoplastic human T cells with unconjugated monoclonal antibodies in SCID mouse chimeras.

The aim of this study was to establish a preclinical in vivo model to evaluate the suppressive effect of unconjugated anti-human T (CD3, 5, 7)-cell monoclonal antibodies (mAb) of mouse IgG2a or rat IgG2b isotype. Therefore, severe combined immunodeficient (SCID) mice were transplanted with human peripheral blood lymphocytes (PBL) of healthy donors (hu-PBL-SCID) or with neoplastic T cells of the human T-ALL cell line Jurkat. In preselected hu-PBL-SCID mice with substantial T cell chimerism single antibody injection caused prompt suppression of circulating human T lymphocytes within 2 days followed by occasional T cell recovery during the following weeks. Furthermore, antibody-mediated T cell suppression was measured by prolonged survival of SCID mice that had been injected with Jurkat cells preadapted to cause 100% mortality within 40 days. Injection of preadapted Jurkat cells caused fatal metastasis in lymphoid as well as non-lymphoid organs. The progression of leukemic cells was successfully suppressed when cells and anti-T cell mAb were given i.p. In contrast to control mice, tumor mortality of antibody-treated animals was delayed or completely suppressed. We conclude that SCID mice with reproducible human T cell chimerism are a relevant animal model to test the suppressive effect of anti-human T cell mAb in preclinical studies.

Animals↗

spalt encodes an evolutionarily conserved zinc finger protein of novel structure which provides homeotic gene function in the head and tail region of the Drosophila embryo.

The region specific homeotic gene spalt (sal) of Drosophila melanogaster promotes the specification of terminal pattern elements as opposed to segments in the trunk. Our results show that the previously reported sal transcription unit was misidentified. Based on P-element mediated germ line transformation and DNA sequence analysis of sal mutant alleles, we identified the transcription unit that carries sal function. sal is located close to the misidentified transcription unit, and it is expressed in similar temporal and spatial patterns during embryogenesis. The sal gene encodes a zinc finger protein of novel structure composed of three widely spaced 'double zinc finger' motifs of internally conserved sequences and a single zinc finger motif of different sequence. Antibodies produced against the sal protein show that sal is first expressed at the blastoderm stage and later in restricted areas of the embryonic nervous system as well as in the developing trachea. The antibodies detect sal homologous proteins in corresponding spatial and temporal patterns in the embryos of related insect species. Sequence analysis of the sal gene of Drosophila virilis, a species which is phylogenetically separated by approximately 60 million years, suggests that the sal function is conserved during evolution, consistent with its proposed role in head formation during arthropod evolution.

Amino Acid Sequence↗

Localized expression of a novel micropia-like element in the blastoderm of Drosophila melanogaster is dependent on the anterior morphogen bicoid.

We have identified a novel transposon-like element of Drosophila melanogaster that is present in approximately 20 copies in the genome. It codes for a polyprotein containing the diagnostic sequence motifs for a nucleic acid binding CCHC protein, a proteinase, a reverse transcriptase and an integrase as typically found in retroviruses. Owing to its early expression in the blastoderm embryo, and its close relationship to micropia, a previously identified Drosophila retrotransposon, we termed the novel element "blastopia". The spatially restricted expression of blastopia transcripts in head anlagen of the blastoderm embryo is under the direct or indirect control of the Drosophila morphogen bicoid, which is normally required to establish the anterior pattern elements in the embryo. Our results suggest that a blastopia element acts as an "enhancer trap", and thereby participates in the control of an as yet unidentified gene normally expressed in the head anlagen of the embryo.

Amino Acid Sequence↗

Determination of monoclonal antibody specificity by immunoadsorption and western blotting.

A rapid and simple method has been developed for identifying the specificity of monoclonal antibodies at an early stage in the production of hybridomas. The technique is a micro-method utilizing biotinylated crude antigen and the surface of microtiter plates as an immunoaffinity matrix. The monoclonal antibodies to be tested are adsorbed to the microtiter wells and incubated with the labeled antigen preparation. Non-specific binding can be reduced by blocking and repeated washing steps. The specific antigen is then eluted by SDS-containing buffers, subjected to SDS-PAGE, blotted onto nitrocellulose and detected by enzyme-labeled avidin in a Western blot assay. The amount of bound and removed antigen can be quantitated by developing eluted and non-eluted control wells by ELISA techniques. Since this ELISA can be performed rapidly, only samples which contain sufficient specific material can be selected for electrophoresis and blotting. The major advantages of the technique are (i) the use of a non-radioactive label resulting in an easy and time-saving procedure, (ii) the possibility of quantitating the amount of captured and detached antigen by ELISA, (iii) the need for only a minimal amount of antigen, (iv) the use of unpurified antibodies of all isotypes, (v) a high signal-to-noise ratio, and (vi) as with all immunoprecipitation techniques, the possibility of detecting SDS-sensitive epitopes and of using crude antigen preparations. Using this method we were able to characterize monoclonal antibodies against both soluble proteins (mouse and human C1q) and membrane determinants (human pan T cell CD5 and CD7).

Animals↗