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Biomedical subjects

R Schweitzer

Publications and source records attributed to R Schweitzer.

At least 19 recordsLinked to original sources
PubMed2001

Cloning and expression of a novel cysteine-rich secreted protein family member expressed in thyroid and pancreatic mesoderm within the chicken embryo.

We have isolated a new chicken gene that is a member of the cysteine-rich secreted protein family (CRISP). The CRISP family is composed of over 70 members that are found in many phyla of organisms, including: vertebrates, plants, fungi, yeast, and insects. Here we describe the cloning of a novel member of this family, SugarCrisp, and its expression pattern throughout chicken embryogenesis. We also describe its utility as a marker of thyroid and pancreatic mesoderm in the developing chicken embryo and its expression within the human and mouse in glandular tissue.

Amino Acid Sequence↗
PubMed2001

Analysis of the tendon cell fate using Scleraxis, a specific marker for tendons and ligaments.

Little is known about the genesis and patterning of tendons and other connective tissues, mostly owing to the absence of early markers. We have found that Scleraxis, a bHLH transcription factor, is a highly specific marker for all the connective tissues that mediate attachment of muscle to bone in chick and mouse, including the limb tendons, and show that early scleraxis expression marks the progenitor cell populations for these tissues. In the early limb bud, the tendon progenitor population is found in the superficial proximomedial mesenchyme. Using the scleraxis gene as a marker we show that these progenitors are induced by ectodermal signals and restricted by bone morphogenetic protein (BMP) signaling within the mesenchyme. Application of Noggin protein antagonizes this endogenous BMP activity and induces ectopic scleraxis expression. However, the presence of excess tendon progenitors does not lead to the production of additional or longer tendons, indicating that additional signals are required for the final formation of a tendon. Finally, we show that the endogenous expression of noggin within the condensing digit cartilage contributes to the induction of distal tendons.

Animals↗
PubMed2000

The role of personality in the development and perpetuation of chronic fatigue syndrome.

OBJECTIVES: Qualitative evidence suggests that personality may have special relevance to the predisposition, precipitation and perpetuation of chronic fatigue syndrome (CFS). This study compares three dimensions of personality - perfectionism, self-esteem, and emotional control in the personality profiles of CFS patients (N=44) and a control group (N=44) without a history of CFS, matched for age and gender. METHODS: Participants were assessed on the MPS [Frost RO, Marten P, Lahart C, Rosenblate R. The dimensions of perfectionism. Cognit Ther Res 1990;14:449-468.]; the Rosenberg Self-Esteem Scale [Rosenberg M. Society and the Adolescent Self-image. Princeton, NJ: Princeton Univ Press, 1965.]; the Courtauld Emotional Scale [Watson M, Greer S. Development of a questionnaire measure of emotional control. J Psychosom Res 1983;27:299-305.] and the Marlowe-Crowne Social Desirability Scale [Crowne DP, Marlowe D. A new scale of social desirability independent of psychopathology. J Consult Psychol 1960;24:349-354.]. RESULTS: Analyses revealed that the CFS group reported higher levels than the control group on the Total Perfectionism score and Doubts about Actions and the Concern over Mistakes subscales. Furthermore, the CFS group also reported lower self-esteem than the control group. No difference between the two groups was found on the dimensions of emotional control and social desirability response bias. CONCLUSION: A developmental model of CFS, which considers the predisposing, precipitating, and perpetuating factors that may account for the course of the disorder irrespective of etiology, is proposed. In the context of the results, recommendations for practice and future research are discussed.

Adolescent↗
PubMed2000

Similar expression and regulation of Gli2 and Gli3 in the chick limb bud.

Gli genes encode a family of zinc finger transcription factors that mediate signaling by Hedgehog proteins. We have cloned the chick Gli3 gene and studied its expression in developing chick limbs. Gli3 expression is highly similar to that of chick Gli2. Gli3 mRNA is evenly distributed in the early limb mesenchyme and subsequently downregulated in the posterior mesenchyme by the polarizing activity of Sonic hedgehog. At later stages, Gli3 is expressed in the distal limb mesenchyme.

Amino Acid Sequence↗
PubMed2000

Decontamination of a Mycoplasma-infected Chlamydia pneumoniae strain by pulmonary passage in SCID mice.

We describe a procedure to eliminate contaminating Mycoplasma from Chlamydia pneumoniae (C. pneumoniae) cultures by pulmonary passage in severe combined immunodeficiency mice (SCID). Four weeks after experimental infection only C. pneumoniae could be cultured from the lungs of the infected animals while Mycoplasma could not be detected any longer, as shown by PCR, culture and transmission electron microscopy (TEM).

Animals↗
PubMed2000

Neutralization of disease associated autoantibodies by an immunoglobulin M- and immunoglobulin A-enriched human intravenous immunoglobulin preparation.

Immunoglobulin preparations enriched with IgM and IgA are used in the therapy of severe bacterial infections and for the treatment of acute graft-versus-host disease, but not as yet, in the treatment of autoimmune diseases. We investigated the potential of an IgM- and IgA-enriched immunoglobulin preparation to neutralize activity autoantibodies from patients with autoimmune diseases. We demonstrate that Pentaglobin(R) was at least as effective as intravenous immunoglobulin (Sandoglobulin(R)) in inhibiting autoantibody activity. Each of the immunoglobulin isotypes present in Pentaglobin(R) may be responsible for the inhibitory effect. Pentaglobin(R) immobilized on an affinity matrix retained the disease associated autoantibodies and interacted with F(ab')2 fragments of IgG autoantibodies. Suppression of autoantibody activity is dependent, at least in part, on idiotypic interactions. The present findings provide a rationale for considering these preparations for the immunomodulation of autoimmune disease.

Autoantibodies↗
PubMed1999

p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development.

The p63 gene, a homologue of the tumour-suppressor p53, is highly expressed in the basal or progenitor layers of many epithelial tissues. Here we report that mice homozygous for a disrupted p63 gene have major defects in their limb, craniofacial and epithelial development. p63 is expressed in the ectodermal surfaces of the limb buds, branchial arches and epidermal appendages, which are all sites of reciprocal signalling that direct morphogenetic patterning of the underlying mesoderm. The limb truncations are due to a failure to maintain the apical ectodermal ridge, a stratified epithelium, essential for limb development. The embryonic epidermis of p63-/- mice undergoes an unusual process of non-regenerative differentiation, culminating in a striking absence of all squamous epithelia and their derivatives, including mammary, lacrymal and salivary glands. Taken together, our results indicate that p63 is critical for maintaining the progenitor-cell populations that are necessary to sustain epithelial development and morphogenesis.

Animals↗
PubMed1999

Digital Imaging as a Detection Method for a Fluorescent Protease Assay in 96-Well and Miniaturized Assay Plate Formats.

The demand to increase throughput in HTS programs, without a concomitant addition to costs, has grown significantly during the past few years. One approach to handle this demand is assay miniaturization, which can provide greater throughput, as well as significant cost savings through reduced reagent costs. Currently, one of the major challenges facing assay miniaturization is the ability to detect the assay signal accurately and rapidly in miniaturized formats. Digital imaging is a detection method that can measure fluorescent or luminescent signals in these miniaturized formats. In this study, an imaging system capable of detecting the signal from a fluorescent protease assay in multiple plate formats was used to evaluate this detection method in an HTS environment. A direct comparison was made between the results obtained from the imaging system and a fluorescent plate reader by screening 8,800 compounds in a 96-well plate format. The imaging system generated similar changes in relative signal for each well in the screen, identified the same active compounds, and yielded similar IC(50) values as compared to the plate reader. When a standard protease inhibitor was evaluated in 96-, 384-, 864-, and 1536-well plates using imaging detection, similar IC(50) values were obtained. Furthermore, similar dose-response curves were generated for the compound in 96- and 384-well assay plates read in a plate reader. These results provide support for digital imaging as an accurate and rapid detection method for high-density microtiter plates.

Journal Article↗
PubMed1998

EGF domain swap converts a drosophila EGF receptor activator into an inhibitor.

In Drosophila the function of the epidermal growth factor (EGF) receptor is modulated zygotically by three EGF-like proteins: Spitz (Spi), which is a potent activator; Vein (Vn), which is a moderate activator; and Argos (Aos), which is an inhibitor. Chimeric molecules were constructed in which the EGF domain of Vn was swapped with the EGF domain from each factor. The modified Vn proteins behaved both in vitro and in vivo with properties characteristic of the factor from which the EGF domain was derived. These results demonstrate that the EGF domain is the key determinant that gives DER inhibitors and activators their distinct properties.

Amino Acid Sequence↗
PubMed1998

Sequential activation of the EGF receptor pathway during Drosophila oogenesis establishes the dorsoventral axis.

Previous work has demonstrated a role for the Drosophila EGF receptor (Torpedo/DER) and its ligand, Gurken, in the determination of anterioposterior and dorsoventral axes of the follicle cells and oocyte. The roles of DER in establishing the polarity of the follicle cells were examined further, by following the expression of DER-target genes. One class of genes (e.g. kekon) is induced by the DER pathway at all stages. Broad expression of kekon at the stage in which the follicle cells migrate posteriorly over the oocyte, demonstrates the capacity of the pathway to pattern all follicle cells except the ventral-most rows. This may provide the spatial coordinates for the ventral-most follicle cell fates. A second group of target genes (e.g. rhomboid (rho)) is induced only at later stages of oogenesis, and may require additional inputs by signals emanating from the anterior, stretch follicle cells. The function of Rho was analyzed by ectopic expression in the stretch follicle cells, and shown to induce a non-autonomous dorsalizing activity that is independent of Gurken. Rho thus appears to be involved in processing a DER ligand in the follicle cells, to pattern the egg chamber and allow persistent activation of the DER pathway during formation of the dorsal appendages.

Animals↗
PubMed1997

A comparison of masticatory function in patients with or without reconstruction of the mandible.

BACKGROUND: The functional benefits of mandibular reconstruction following a composite resection remain unclear. Although microvascular surgical techniques have dramatically increased the predictability of bone and soft-tissue reconstruction towards presurgical anatomic norms, the specific factors responsible for improved function remain controversial. Objective measures of masticatory function need to be more clearly determined before the predictability and efficacy of reconstructive approaches is established. METHODS: We evaluated objective measures of oral function and patient reports of function in 10 reconstructed mandibulectomy patients, 10 without reconstruction, and 10 controls. Measures of oral function included bite force assessed at the first molar and incisal edge, a measure of tongue and cheek function, and patient reports of food they could eat. RESULTS: Both reconstructed and nonreconstructed patients presented decreased biting force, a more restricted diet, and compromised cheek and tongue function as compared with normals. However, reconstructed patients had significantly better measures of tongue function and ability to eat a varied diet than did nonreconstructed patients. Of the objective measures used to measure masticatory performance, bite force was poorly correlated, whereas measures of tongue function strongly correlated with successful mastication. CONCLUSION: Both reconstructed and nonreconstructed patients presented with a significant functional deficit when compared with normals, with reconstructed patients having better overall function than nonreconstructed patients.

Aged↗
PubMed1997

Plasma carotenoids in German children and adolescents.

UNLABELLED: Carotenoids are important antioxidants and precursors of vitamin A, but only few studies have been carried out on plasma carotenoid levels in paediatric age groups. Using high-performance liquid chromatography we analysed concentrations of four important carotenoids (alpha-carotene, beta-carotene, cryptoxanthin, lycopene) in 129 healthy German children and adolescents (81 boys, 48 girls; age 1-18 years). For all carotenoids analysed, no significant differences between girls and boys were found. alpha-Carotene values ranged from 0 mumol/l (below detection limits) to 0.73 mumol/l (0-395 micrograms/l), beta-carotene from 0.09 mumol/l to 2.68 mumol/l (48-1443 micrograms/l), lycopene from 0 mumol/l to 1.51 mumol/l (0-815 micrograms/l), and cryptoxanthin from 0 mumol/l to 0.30 mumol/l (0-164 micrograms/l), respectively. Data analyses according to age groups showed a tendency towards higher levels of alpha- and beta-carotene, and lower levels of lycopene in young children. These differences were significant when children younger than 4 years were compared with those above 8 and 12 years, respectively. The data presented may serve as reference values for studies on children with nutritional disorders and diseases associated with a risk of vitamin deficiencies. CONCLUSION: Carotenoids are important antioxidants and singlet oxygen scavengers. Plasma levels of alpha-carotene, beta-carotene, lycopene and cryptoxanthin were determined in 129 healthy German children and adolescents. Highest values were found for beta-carotene and lycopene.

Adolescent↗
PubMed1997

A thousand and one roles for the Drosophila EGF receptor.

In the Drosophila genome there is a single member of the EGF receptor tyrosine kinase family. This receptor fulfills multiple roles during development, as reflected by the many designations given to mutant alleles in the locus (Egfr, DER, faint little ball, torpedo and Ellipse). The full scope of EGFR functions became apparent only in recent years: receptor activation was shown to have an instructive role in successive cell fate determination events during oogenesis, embryogenesis, and the proliferation and differentiation of imaginal discs. To ensure the fidelity of these processes, the precise place and time of receptor activation are tightly regulated by the localized presentation of activating ligands, in conjunction with a negative-feedback loop generated by an inhibitory secreted factor. The cellular mechanisms that translate EGFR activation to discrete cell fates are now the focus of intense studies.

Animals↗
PubMed1996

Argos transcription is induced by the Drosophila EGF receptor pathway to form an inhibitory feedback loop.

Argos is a secreted molecule with an atypical EGF motif. It was recently shown to function as an inhibitor of the signaling triggered by the Drosophila EGF receptor (DER). In this work, we determine the contribution of Argos to the establishment of cell fates in the embryonic ventral ectoderm. Graded activation of DER is essential for patterning the ventral ectoderm. argos mutant embryos show expansion of ventral cell fates suggesting hyperactivation of the DER pathway. In the embryonic ventral ectoderm, argos is expressed in the ventralmost row of cells. We show that argos expression in the ventral ectoderm is induced by the DER pathway: argos is not expressed in DER mutant embryos, while it is ectopically expressed in the entire ventral ectoderm following ubiquitous activation of the DER pathway. argos expression appears to be triggered directly by the DER pathway, since induction can also be observed in cell culture, following activation of DER by its ligand, Spitz. Argos therefore functions in a sequential manner, to restrict the duration and level of DER signaling. This type of inhibitory feedback loop may represent a general paradigm for signaling pathways inducing diverse cell fates within a population of non-committed cells.

Animals↗
PubMed1995

Inhibition of Drosophila EGF receptor activation by the secreted protein Argos.

The Drosophila homologue of the mammalian epidermal growth factor (EGF) receptor (DER) is a receptor tyrosine kinase involved in many stages of fly development, including photoreceptor determination, and wing-vein formation. Its primary activating ligand is the Spitz protein, which is similar to mammalian TGF-alpha. Argos is a secreted protein that, like Spitz, contains a single EGF motif. It is a repressor of cell determination in the eye, and acts in other tissues, including the wing. Because Argos has the opposite effects to DER in the eye (the former blocks photoreceptor determination, the latter promotes it) we have tested whether it acts by blocking the DER pathway. We show that Argos does indeed repress this pathway in vivo and find that, in vitro, Argos protein can inhibit the activation of DER by Spitz. Thus the determination of cells by the DER pathway is regulated by a balance between extracellular activating and inhibiting signals. This is the first in vivo example of an extracellular inhibitor of a receptor tyrosine kinase.

Animals↗