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Biomedical subjects

C Schubert

Publications and source records attributed to C Schubert.

At least 37 records · Page 2Linked to original sources
PubMed2000

Chronic pelvic pain and previous sexual abuse.

OBJECTIVE: To determine whether there is an association between history of sexual abuse and development of chronic pelvic pain. METHODS: We studied 36 women with chronic pelvic pain, 23 with chronic low back pain, and 20 healthy women with reference to experience of sexual abuse, physical violence, and emotional neglect in childhood. Semistructured interviews were used to collect data. Assessment of severity of sexual abuse was based on Russell's criteria, and emotional and physical abuse were determined according to Briere's and Adler's definitions, respectively. RESULTS: In terms of experience of sexual abuse in general, the three groups did not differ statistically significantly from each other (P =.128). However, 22% of patients with chronic pelvic pain were sexually abused before their 15th birthdays, significantly more frequently than the other two groups (chronic low back pain 0%, P =.019, pain-free control 0%, P =.028). Women with chronic pelvic pain were exposed more frequently to physical violence (38%) and suffered more emotional neglect (25%) in their childhoods than women in the pain-free control group (physical abuse 5%, P =.012; emotional abuse 0%, P =.018). With regard to physical abuse and emotional neglect, the women with chronic pelvic pain did not differ from those with chronic low back pain (physical abuse 30.4%, P =.385; emotional abuse 21.7%, P =.571). CONCLUSION: Besides physical and emotional trauma, there is a significant association between sexual victimization before age 15 years and later chronic pelvic pain.

Adolescent↗
PubMed2000

Immune reaction links disease progression in cancer patients with depression.

Mood disturbances and depression are supposed to have a negative impact on patients' outcome in malignant tumour disease. On the other hand, poor prognosis in cancer patients is associated with chronic immune challenge which is paralleled by enhanced degradation of the essential amino acid tryptophan and thus decreased plasma tryptophan concentrations. Because tryptophan is precursor for the biosynthesis of the neurotransmitter serotonin (= 5-hydroxytryptamine, 5HT), low tryptophan concentrations will lead to decreased availability of serotonin which finally increases the susceptibility for the development of mood disturbances and depression in the patients. Thus, the development of depression in cancer patients may result from chronic cellular immune stimulation. In conclusion, a more aggressive tumour rather than depression will be responsible for worse outcome of cancer patients and will be associated with a more drastic challenge of the immune system, as a side effect leading to neurotransmitter disturbances.

Depression↗
PubMed2000

Diode laser radiation and its bactericidal effect in root canal wall dentin.

OBJECTIVES: The aim of this study was to investigate the antibacterial effect of a diode laser in deep root canal dentin. BACKGROUND DATA: The microbial colonization of root canal dentin can lead to failures in conventional endodontic treatment if an inadequate bacterial reduction only is achieved through canal treatment and chemical disinfection. METHODS: 100 microm, 300 microm and 500 microm bovine dentin slices obtained by longitudinal sections were sterilized and inoculated on one side with an Enterococcus faecalis suspension. Laser radiation was performed on the opposite side with the diode laser (810 nm) at a setting of 3 W in continuous mode (CW). Radiation was performed using a 400-microm tapered fiber tip at an angle of approximately 5 degrees to the surface over a period of 30 seconds. The output power at the distal end of the tip was 0.6 W. The bacteria were then eluted through vibration and cultured on blood agar plates. The colony count reflected the antibacterial effect of laser radiation as a function of the layer thickness. RESULTS: A mean bacterial reduction of 74% was achieved even with a 500-microm thick slice. CONCLUSION: This investigation indicates that the diode laser radiation reduces the number of bacteria in deep layers of infected root canal wall dentin.

Animals↗
PubMed1999

Characterization of glycosylphosphatidylinositol-linked molecule CD55/decay-accelerating factor as the receptor for antibody SC-1-induced apoptosis.

The human monoclonal antibody SC-1 induces apoptosis of stomach carcinoma cells and is currently used in a clinical Phase II trial. The antibody binds to a target molecule that is preferentially expressed on diffuse- and intestinal-type stomach cancer cells and shows a very restricted expression on other normal and malignant tissues. In this paper, we show that the SC-1 receptor is a stomach carcinoma-associated isoform of CD55 [membrane-bound decay-accelerating factor (DAF)-B] with a relative molecular mass of approximately 82 kDa. The antigenic site of SC-1 is an N-linked carbohydrate residue. Cross-linking of the DAF receptor increases apoptotic activity. SC-1 binding induces tyrosine phosphorylation of three proteins of approximately 60, 75, and 110 kDa, whereas a serine residue of an approximately 35-kDa protein is dephosphorylated. Expression of caspase-3 (CPP32) and caspase-8 (FLICE) is elevated, and activation of these caspases occurs. These data show that a tumor-specific variant form DAF is involved in apoptosis and can be used for adjuvant therapeutical purposes on gastric carcinoma.

Antibodies, Monoclonal↗
PubMed1999

Visual arrestin activity may be regulated by self-association.

Visual arrestin is the protein responsible for rapid quenching of G-protein-coupled receptor signaling. Arrestin exists as a latent inhibitor which must be 'activated' upon contact with a phosphorylated receptor. X-ray crystal structures of visual arrestin exhibit a tetrameric arrangement wherein an asymmetric dimer with an extensive interface between conformationally different subunits is related to a second asymmetric dimer by a local two-fold rotation axis. To test the biological relevance of this molecular organization in solution, we carried out a sedimentation equilibrium analysis of arrestin at both crystallographic and physiological protein concentrations. While the tetrameric form can exist at the high concentrations used in crystallography experiments, we find that arrestin participates in a monomer/dimer equilibrium at concentrations more likely to be physiologically relevant. Solution interaction analysis of a proteolytically modified, constitutively active form of arrestin shows diminished dimerization. We propose that self-association of arrestin may provide a mechanism for regulation of arrestin activity by (i) ensuring an adequate supply for rapid quenching of the visual signal and (ii) limiting the availability of active monomeric species, thereby preventing inappropriate signal termination.

Animals↗
PubMed1999

How does arrestin respond to the phosphorylated state of rhodopsin?

Visual arrestin quenches light-induced signaling by binding to light-activated, phosphorylated rhodopsin (P-Rh*). Here we present structure-function data, which in conjunction with the refined crystal structure of arrestin (Hirsch, J. A., Schubert, C., Gurevich, V. V., and Sigler, P. B. (1999) Cell, in press), support a model for the conversion of a basal or "inactive" conformation of free arrestin to one that can bind to and inhibit the light activated receptor. The trigger for this transition is an interaction of the phosphorylated COOH-terminal segment of the receptor with arrestin that disrupts intramolecular interactions, including a hydrogen-bonded network of buried, charged side chains, referred to as the "polar core." This disruption permits structural adjustments that allow arrestin to bind to the receptor. Our mutational survey identifies residues in arrestin (Arg175, Asp30, Asp296, Asp303, Arg382), which when altered bypass the need for the interaction with the receptor's phosphopeptide, enabling arrestin to bind to activated, nonphosphorylated rhodopsin (Rh*). These mutational changes disrupt interactions and substructures which the crystallographic model and previous biochemical studies have shown are responsible for maintaining the inactive state. The molecular basis for these disruptions was confirmed by successfully introducing structure-based second site substitutions that restored the critical interactions. The nearly absolute conservation of the mutagenically sensitive residues throughout the arrestin family suggests that this mechanism is likely to be applicable to arrestin-mediated desensitization of most G-protein-coupled receptors.

Animals↗
PubMed1999

The 2.8 A crystal structure of visual arrestin: a model for arrestin's regulation.

G protein-coupled signaling is utilized by a wide variety of eukaryotes for communicating information from the extracellular environment. Signal termination is achieved by the action of the arrestins, which bind to activated, phosphorylated G protein-coupled receptors. We describe here crystallographic studies of visual arrestin in its basal conformation. The salient features of the structure are a bipartite molecule with an unusual polar core. This core is stabilized in part by an extended carboxy-terminal tail that locks the molecule into an inactive state. In addition, arrestin is found to be a dimer of two asymmetric molecules, suggesting an intrinsic conformational plasticity. In conjunction with biochemical and mutagenesis data, we propose a molecular mechanism by which arrestin is activated for receptor binding.

Amino Acid Sequence↗
PubMed1999

Differences in morphology and cytoskeleton of MCF-7 and MX-1 cells after therapy with OH-tamoxifen and the pure estrogen antagonist ZM 182780. An immunofluorescence and scanning electron microscopic study.

The adjuvant endocrine therapy of breast cancer with non-steroidal antiestrogens of the triphenylethylene-type such as tamoxifen is clinically well established, and pure steroidal antiestrogens are being introduced in clinical trials to circumvent the probable occurrence of tamoxifen resistance. Nevertheless, there do still remain some unsolved questions about the exact mechanisms of these substances. We therefore investigated the different effects of 4-OH-Tamoxifen (OHT), a non-steroidal antiestrogen, versus ZM 182780, a pure steroidal antiestrogen, on the morphology and on the cytoskeleton of MCF-7 (estrogen receptor-positive) and MX-1 (estrogen receptor-negative) cells. For this purpose cells were treated for 2, 5 and 7 days with OHT, ZM182780 and different concentrations of beta-estradiol. Interestingly, in scanning electron microscopy, MCF-7 cells showed more differentiation by forming three-dimensional structures such as acini or tubule-like structures under ZM 182780 therapy than with OHT. As expected, MX-1 cells showed no effects after ZM 182780-therapy, but OHT led to a decrease in the number of these cells and produced a fibroblast-like appearance of the estrogen receptor-negative MX-1 cells. The following immunocytochemical experiments on the tubulin, vimentin, cytokeratin and actin cytoskeleton surprisingly did not show marked differences within the morphologically differentiated ZM 182780-treated population compared to the control group of MCF-7 cells. Only the OHT-treated cells of both, the ER(+) and the ER(-) cells, showed a rearrangement of actin filaments and cytokeratin which appeared even more pronounced within the ER(-) MX-1 cells. No experimental group showed morphologically detectable changes in tubulin or vimentin distribution. These data suggest a non ER-mediated OHT-effect on the cytoskeleton that also affects the ER(-) cell line MX-1.

Actins↗
PubMed1999

MAPKAP kinase 2 is essential for LPS-induced TNF-alpha biosynthesis.

MAPKAP kinase 2 (MK2) is one of several kinases that are regulated through direct phosphorylation by p38 MAP kinase. By introducing a targeted mutation into the mouse MK2 gene, we have determined the physiological function of MK2 in vivo. Mice that lack MK2 show increased stress resistance and survive LPS-induced endotoxic shock. This is due to a reduction of approximately 90% in the production of tumor necrosis factor-alpha (TNF-alpha) and not to a change in signalling from the TNF receptor. The level and stability of TNF-alpha mRNA is not reduced and TNF-alpha secretion is not affected. We conclude that MK2 is an essential component in the inflammatory response which regulates biosynthesis of TNF-alpha at a post-transcriptional level.

Animals↗
PubMed1999

Differential expression of CD34 and Ki-M1p in pleomorphic fibroma and dermatofibroma with monster cells.

Pleomorphic fibroma (PF) and dermatofibroma with monster cells (DFMC) are characterized by the presence of numerous cells with large atypical nuclei. Despite cytologic similarities, the two entities are likely to be unrelated, but their histogenesis is poorly understood. In this study, we examined six cases of PF and eleven cases of DFMC by immunohistochemistry using antibodies against vimentin, alpha-smooth muscle actin, S-100 protein, CD34, factor XIIIa, and the pan-monocytic marker Ki-M1p. Strong vimentin expression was seen in all tumors, whereas none of them expressed S-100 protein. PF consistently exhibited CD34 staining but appeared to be depleted of Ki-M1p positive cells compared with the surrounding normal skin. Conversely, all cases of DFMC contained numerous Ki-M1p positive cells including atypical multinucleate cells, but virtually no CD34 reactivity was observed. A weak staining for alpha-smooth muscle actin was occasionally seen in a subset of the cells of both entities. Our results indicate that PF and DFMC are histogenetically distinct entities that may arise from two different types of dermal dendritic cells defined by their reactivity for CD34 and Ki-M1p, respectively. Immunohistochemistry using these two antibodies permits an easy and reliable discrimination between PF and DFMC.

Actins↗
PubMed1999

Structural changes of human epidermis induced by human leukocyte-derived proteases.

During the process of inflammation human neutrophils release potent serine proteases, such as human leukocyte elastase and cathepsin G. In psoriasis these enzymes are released within the epidermis. To investigate the destructive potential of neutrophil-derived serine proteases these were applied on viable human epidermis as well as full thickness human skin in vitro. Human leukocyte elastase and cathepsin G were found to dissociate keratinocytes from epidermal sheets in a time- and dose-dependent fashion. Significant keratinocyte dissociation was observed 4 h after application of 3 nM human leukocyte elastase. By electron microscopy of elastase- or cathepsin G-treated full thickness human skin, widening of the extracellular space followed by complete separation of keratinocytes without intradesmosomal cleavage was observed. In addition, cathepsin G induced membrane damage as well as destruction of intracellular organelles. Thus, neutrophil-derived serine proteases exert pronounced destructive potential in human epidermis in concentrations likely to appear in lesional psoriatic skin.

Cathepsin G↗
PubMed1998

Genetic requirements for PIE-1 localization and inhibition of gene expression in the embryonic germ lineage of Caenorhabditis elegans.

In early Caenorhabditis elegans embryos, production of new mRNAs is inhibited in the germ lineage. This inhibition requires the germline factor PIE-1, and correlates with the absence in germline blastomeres of a phosphoepitope on RNA polymerase II (RNAPII-H5). We show that PIE-1 is uniformly distributed in oocytes and newly fertilized eggs, and becomes localized asymmetrically in the late one-cell stage. To begin to dissect the mechanisms required for PIE-1 localization and inhibition of RNAPII-H5 expression, we have examined the distribution of PIE-1 and RNAPII-H5 in maternal-effect mutants that disrupt embryonic development. We find that mutants that disrupt the asymmetric divisions of germline blastomeres mislocalize PIE-1, and activate RNAPII-H5 expression in the germ lineage. In contrast, mutants that alter somatic cell identities do not affect PIE-1 localization or RNAPII-H5 expression. Our observations suggest that PIE-1 represses mRNA transcription in each germline blastomere in a concentration-dependent manner. We also show that in wild-type, and in mutants where PIE-1 is mislocalized, the cellular and subcellular distribution of PIE-1 remarkably parallels that of the P granules, suggesting that the localizations of these two germline components are coordinately regulated.

Animals↗
PubMed1998

Giant cell collagenoma: a benign dermal tumor with distinctive multinucleate cells.

We present five cases of a hitherto unreported cutaneous neoplasm. The tumors appeared as solitary slow-growing flesh-colored nodules arising in young and middle-aged adults. They were located on the trunk, the upper extremities, and the face, and did not recur after complete excision. Clinically, they were diagnosed as dermal nevus, Spitz's nevus, fibroma, or neurofibroma. Histology revealed polypoid flat-dome-shaped lesions with a sharply demarcated matrix consisting of coarse hyalinized collagen bundles arranged in a prominent storiform pattern and separated by mucin-containing clefts. Despite a low overall cellularity, the tumors contained numerous, occasionally bizarre-shaped, multinucleate giant cells with crowded vesicular nuclei and a pale staining foamy cytoplasm, as well as plump fibroblastlike cells with analogous nuclear morphology. Atypical nuclei or mitotic figures were not observed. The cells were strongly positive for vimentin but negative for cytokeratin, smooth muscle actin, desmin, S-100 protein, CD34, factor XIIIa, and the macrophage markers KP1, Mac 387, and Ki-M1p, suggesting a fibroblastic origin. Based on the overall architecture, we conclude that these tumors probably represent a distinctive variant of solitary circumscribed storiform collagenoma (sclerotic fibroma) and propose the designation of giant cell collagenoma.

Adult↗
PubMed1998

Gastrointestinal upsets and new copper plumbing--is there a connection?

This article summarizes two investigations that examine the health effects of prolonged exposure to copper-contaminated drinking water. The first study was initiated after elevated copper levels were detected in several homes that were either newly constructed or recently remodeled. All of these homes were served by the same municipal water supplier. The second case involved illnesses and water-quality problems that were reported by several residents of a mobile home park shortly after a new water distribution system was installed. Findings from these investigations suggest that copper-contaminated drinking water may be a fairly common cause of nausea, diarrhea, abdominal cramps, and headaches-especially among residents of new or recently-remodeled homes, and in areas where water supplies are naturally corrosive.

Adolescent↗
PubMed1997

Proliferation marker Ki-S5 as a diagnostic tool in melanocytic lesions.

BACKGROUND: A discrimination between benign and malignant melanocytic lesions is not always possible by conventional histology. OBJECTIVE: Our purpose was to determine the proliferative activity in various types of melanocytic neoplasms and to appraise its value as a diagnostic adjunct. METHODS: The growth fraction was assessed immunohistochemically in 398 melanocytic lesions by means of the monoclonal antibody Ki-S5 directed to the Ki-67 antigen. In this way, a cut-off level was defined and applied to 112 lesions of equivocal histology. The revised diagnoses were correlated to the clinical courses. RESULTS: Common nevi, Spitz nevi, and melanomas exhibited significantly different proliferation indices and distinctive distribution patterns of cycling cells. In agreement, malignancy diagnosed on the basis of a growth fraction greater than 5% was confirmed by disease progression in 68% of our cases with uncertain diagnosis. CONCLUSION: Determination of the proliferative activity in melanocytic lesions may usefully complement conventional histology to improve diagnostic accuracy.

Antibodies, Monoclonal↗