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Biomedical subjects

B Weinhold

Publications and source records attributed to B Weinhold.

At least 19 recordsLinked to original sources
PubMed2004

Soluble serum E-cadherin as a marker of tumour progression in colorectal cancer patients.

A pilot study was conducted to determine the concentrations of soluble serum E-cadherin in 36 patients with colorectal cancer or a high-grade dysplasia by the use of an ELISA technique. The results were compared with staging characteristics and concentrations of routine serum carcinoembryonic antigen (CEA). Sixteen patients with benign diseases and nine healthy volunteers served as internal or negative controls. Tumour specimens from seven patients were analysed by immunohistochemistry to compare concentrations of soluble serum E-cadherin with patterns of cell-bound E-cadherin or beta-catenin. Serum E-cadherin concentrations were increased in colorectal cancer patients (P = 0.009), but also in benign disease controls (P = 0.005), correlating with the T- (P < 0.05), but not N- or M-stage, and with serum CEA (P = 0.002) in case of existing liver metastases. Compared with other staining patterns, concentrations of soluble serum E-cadherin were higher in case of an exclusive membrane-bound localization of cellular beta-catenin (P = 0.071). The results suggest marker characteristics of soluble serum E-cadherin in colorectal cancer patients, but lacking specificity argues against a routine clinical use.

Biomarkers, Tumor↗
PubMed2001

Serum response factor is required for immediate-early gene activation yet is dispensable for proliferation of embryonic stem cells.

Addition of serum to mitogen-starved cells activates the cellular immediate-early gene (IEG) response. Serum response factor (SRF) contributes to such mitogen-stimulated transcriptional induction of many IEGs during the G0-G1 cell cycle transition. SRF is also believed to be essential for cell cycle progression, as impairment of SRF activity by specific antisera or antisense RNA has previously been shown to block mammalian cell proliferation. In contrast, Srf(-/-) mouse embryos grow and develop up to E6.0. Using the embryonic stem (ES) cell system, we demonstrate here that wild-type ES cells do not undergo complete cell cycle arrest upon serum withdrawal but that they can mount an efficient IEG response. This IEG response, however, is severely impaired in Srf(-/-) ES cells, providing the first genetic proof that IEG activation is dependent upon SRF. Also, Srf(-/-) ES cells display altered cellular morphology, reduced cortical actin expression, and an impaired plating efficiency on gelatin. Yet, despite these defects, the proliferation rates of Srf(-/-) ES cells are not substantially altered, demonstrating that SRF function is not required for ES cell cycle progression.

Animals↗
PubMed2001

Invitation to a shared community ministry.

Health care reform presents new challenges as community clergy, health care chaplains, and parish nurses seek to provide spiritual care. This contribution describes both the advantages and barriers to a shared community ministry. Collaboration among these professionals can provide an important continuum of spiritual care. Health care chaplains can serve as a vital link between patients and their other spiritual caregivers. They should welcome community clergy as part of the healing team and offer resources such as residency programs and seminars. Parish nurses can expand the health ministry of the church and help community clergy and chaplains provide spiritual support. The skills and gifts of each can weave a shared community ministry to provide a holistic approach to the spiritual needs of congregants.

Chaplaincy Service, Hospital↗
PubMed2000

Srf(-/-) ES cells display non-cell-autonomous impairment in mesodermal differentiation.

The serum response factor (SRF) transcription factor is essential for murine embryogenesis. SRF+(-/-) embryos stop developing at the onset of gastrulation, lacking detectable mesoderm. This developmental defect may reflect cell-autonomous impairment of SRF(-/-) embryonic cells in mesoderm formation. Alternatively, it may be caused by a non-cell-autonomous defect superimposed upon inappropriate provision of mesoderm-inducing signals to primitive ectodermal cells. We demonstrate that the ability of SRF(-/-) embryonic stem (ES) cells to differentiate in vitro into mesodermal cells is indeed impaired. However, this impairment can be modulated by external, cell-independent factors. Retinoic acid, but not dimethylsulfoxide, permitted activation of the mesodermal marker gene T(Bra), which was also activated when SRF was expressed in SRF(-/-) ES cells. Embryoid bodies from SRF(-/-) ES cell aggregates also activated mesodermal marker genes, but displayed unusual morphologies and impairment in cavitation. Finally, in nude mice, Srf(-/-) ES cells readily differentiated into mesodermal cells of SRF(-/-) genotype, including cartilage, bone or muscle cells. We demonstrate that SRF contributes to mesodermal gene expression of ES cells and that SRF(-/-) ES cells display a non-cell-autonomous defect in differentiation towards mesoderm.

Animals↗
PubMed1998

Serum response factor is essential for mesoderm formation during mouse embryogenesis.

The transcription factor serum response factor (SRF), a phylogenetically conserved nuclear protein, mediates the rapid transcriptional response to extracellular stimuli, e.g. growth and differentiation signals. DNA- protein complexes containing SRF or its homologues function as nuclear targets of the Ras/MAPK signalling network, thereby directing gene activities associated with processes as diverse as pheromone signalling, cell-cycle progression (transitions G0-G1 and G2-M), neuronal synaptic transmission and muscle cell differentiation. So far, the activity of mammalian SRF has been studied exclusively in cultured cells. To study SRF function in a multicellular organism we generated an Srf null allele in mice. SRF-deficient embryos (Srf -/-) have a severe gastrulation defect and do not develop to term. They consist of misfolded ectodermal and endodermal cell layers, do not form a primitive streak or any detectable mesodermal cells and fail to express the developmental marker genes Bra (T), Bmp-2/4 and Shh. Activation of the SRF-regulated immediate early genes Egr-1 and c-fos, as well as the alpha-Actin gene, is severely impaired. Our study identifies SRF as a new and essential regulator of mammalian mesoderm formation. We therefore suggest that in mammals Ras/MAPK signalling contributes to mesoderm induction, as is the case in amphibia.

Animals↗
PubMed1997

Interleukin-6-dependent and -independent regulation of the human C-reactive protein gene.

We have investigated the function of different mediators of the regulation of the human C-reactive protein (hCRP) gene in transgenic mice. hCRP was induced by lipopolysaccharide and wounding in interleukin-6 (IL-6) +/+ mice, but not in IL-6 -/- mice. This finding suggested that IL-6 is necessary for the induction of hCRP. However, injection of IL-6 did not induce the hCRP gene. Thus, the induction of hCRP by IL-6 seems to require an additional cofactor. Therefore, we screened different cytokines for their activity in IL-6 +/+ and IL-6 -/- mice. Surprisingly, interleukin-1beta, as well as oncostatin M or leukaemia inhibitory factor, led to an induction of hCRP in both genetic backgrounds. These results indicate an IL-6-dependent and -independent regulation of hCRP. These hCRP transgenic mice therefore represent a novel model system for defining the cytokine network involved in the regulation of acute-phase genes during the course of inflammation.

Animals↗
PubMed1997

Interleukin-6 is necessary, but not sufficient, for induction of the humanC-reactive protein gene in vivo.

We have investigated the involvement of interleukin-6 (IL-6) in the induction of the gene encoding the acute-phase protein human C-reactive protein (hCRP). In transgenic mice the hCRP gene can be induced by lipopolysaccharide (LPS), but not by IL-6. In contrast, hCRP was inducible by IL-6 in primary human hepatocytes and in primary hepatocytes isolated from transgenic mice. To further evaluate the role of IL-6, we introduced the hCRP transgene into animals lacking endogenous IL-6 (IL-6-negative mice). Here, hCRP was not inducible by LPS, but was induced by a combination of LPS and IL-6. These results clearly demonstrate that IL-6 is necessary, but not sufficient, for the induction of hCRP expression. These animal models will allow further dissection of the cytokine network responsible for the regulation of the major human acute-phase reactant CRP.

Animals↗
PubMed1997

Role of interleukin-6 in mediating mesangial cell proliferation and matrix production in vivo.

Mesangial cell proliferation and matrix overproduction characterize many progressive glomerular diseases. Based on currently available data, the role of interleukin-6 (IL-6) in mediating mesangial cell proliferation and matrix production is controversial. The present study attempts to clarify this issue by showing that: (1) IL-6 knock out mice develop a normal glomerular architecture and in particular a normal mesangium. (2) Mesangioproliferative glomerulonephritis induced by Habu snake venom is equally severe in IL-6 knock out mice as in control mice. (3) A continuous seven-day intraperitoneal infusion of 50 micrograms recombinant human IL-6 into rats with a prior minimal (subnephritogenic) injury to mesangial cells does not induce glomerular cell activation, cell proliferation, matrix production, leukocyte influx, platelet influx or proteinuria. (4) A continuous seven-day IL-6 infusion into rats with mesangioproliferative nephritis (anti-Thy 1.1 nephritis) increases matrix protein transcription in the absence of detectable effects on matrix protein accumulation and otherwise has no effect on the natural course of the disease. We conclude from these findings that IL-6 is not an important mediator of mesangial cell proliferation and matrix overproduction in vivo, and that currently little rationale exists to advocate anti-IL-6 therapy in mesangioproliferative disease states.

Animals↗