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Biomedical subjects

Carol Stocking

Publications and source records attributed to Carol Stocking.

27 records · Page 2Linked to original sources
PubMed2003

Palliative Excellence in Alzheimer Care Efforts (PEACE): a program description.

Hospice is the standard method for providing quality end-of-life care in the United States. However, studies reveal that persons with dementia are infrequently referred to hospice, that barriers exist to increasing hospice utilization in this population, and that patients with dementia would benefit from hospice or hospice-like services earlier in the disease course. The Palliative Excellence in Alzheimer Care Efforts (PEACE) program responds to these deficiencies, striving to improve end-of-life care of persons with dementia and to integrate palliative care into the primary care of patients with dementia throughout the course of the illness. The PEACE program is a disease management model for dementia that incorporates advance planning, patient-centered care, family support, and a palliative care focus from the diagnosis of dementia through its terminal stages. PEACE is coordinated through the primary care geriatrics practice of the University of Chicago. Patients and caregivers are interviewed every 6 months for 2 years, and a postdeath interview is conducted with caregivers. These interviews assess care domains important for the optimal care of persons with dementia and their caregivers. A nurse coordinator reviews interviews and provides feedback to physicians, facilitating enhanced individual care and continuous quality improvement for the practice. Initial feedback suggests patients have adequate pain control, satisfaction with quality of care, appropriate attention to prior stated wishes, and death occurring in the patient's location of choice. Families voiced similar high marks regarding quality of care. This program demonstrates an innovative model of providing quality palliative care for dementia patients and their caregivers.

Alzheimer Disease↗
PubMed2003

Sodium-dependent myo-inositol transporter 1 is a cellular receptor for Mus cervicolor M813 murine leukemia virus.

Retrovirus infection is initiated by binding of the surface (SU) portion of the viral envelope glycoprotein (Env) to specific receptors on cells. This binding triggers conformational changes in the transmembrane portion of Env, leading to membrane fusion and cell entry, and is thus a major determinant of retrovirus tissue and species tropism. The M813 murine leukemia virus (MuLV) is a highly fusogenic gammaretrovirus, isolated from Mus cervicolor, whose host range is limited to mouse cells. To delineate the molecular mechanisms of its restricted host range and its high fusogenic potential, we initiated studies to characterize the cell surface protein that mediates M813 infection. Screening of the T31 mouse-hamster radiation hybrid panel for M813 infectivity localized the receptor gene to the distal end of mouse chromosome 16. Expression of one of the likely candidate genes (slc5a3) within this region in human cells conferred susceptibility to both M813 infection and M813-induced fusogenicity. slc5a3 encodes sodium myo-inositol transporter 1 (SMIT1), thus adding another sodium-dependent transporter to the growing list of proteins used by MuLVs for cell entry. Characterization of SMIT1 orthologues in different species identified several amino acid variations within two extracellular loops that may restrict susceptibility to M813 infection.

Amino Acid Sequence↗
PubMed2002

AML1-ETO inhibits maturation of multiple lymphohematopoietic lineages and induces myeloblast transformation in synergy with ICSBP deficiency.

The translocation (8;21), generating the AML1-ETO fusion protein, is one of the most frequent chromosomal abnormalities associated with acute myelogenous leukemia (AML). To elucidate its role in oncogenesis, bone marrow (BM) cells were infected with a retroviral vector carrying AML1-ETO and transplanted into mice. In contrast to previous transgenic mouse models, we show that AML1-ETO directly stimulates granulopoiesis, suppresses erythropoiesis, and impairs the maturation of myeloid, B, and T lymphoid cells in vivo. To determine the significance of earlier findings that expression of the tumor suppressor ICSBP is often downregulated in AML myeloblasts, AML1-ETO was introduced into BM cells derived from mice lacking the interferon regulatory factor ICSBP. Our findings demonstrate that AML1-ETO synergizes with an ICSBP deficiency to induce myeloblastic transformation in the BM, reminiscent of AML.

Animals↗
PubMed2002

Unmodified Cre recombinase crosses the membrane.

Site-specific recombination in genetically modified cells can be achieved by the activity of Cre recombinase from bacteriophage P1. Commonly an expression vector encoding Cre is introduced into cells; however, this can lead to undesired side-effects. Therefore, we tested whether cell-permeable Cre fusion proteins can be directly used for lox-specific recombination in a cell line tailored to shift from red to green fluorescence after loxP-specific recombination. Comparison of purified recombinant Cre proteins with and without a heterologous 'protein transduction domain' surprisingly showed that the unmodified Cre recombinase already possesses an intrinsic ability to cross the membrane border. Addition of purified recombinant Cre enyzme to primary bone marrow cells isolated from transgenic C/EBPalpha(fl/fl) mice also led to excision of the 'floxed' C/EBPalpha gene, thus demonstrating its potential for in vivo applications. We conclude that Cre enyzme itself or its intrinsic membrane-permeating moiety are attractive tools for direct manipulation of mammalian cells.

Animals↗
PubMed2002

Disabled-2 is transcriptionally regulated by ICSBP and augments macrophage spreading and adhesion.

Mice lacking transcription factor interferon consensus sequence binding protein (ICSBP) develop a syndrome similar to human chronic myeloid leukemia and are immunodeficient. In order to define the molecular mechanisms responsible for the cellular defects of ICSBP(-/-) mice, we used bone marrow-derived macrophages (BMM) to identify genes deregulated in the absence of ICSBP. Here, we report that disabled-2 (Dab2), a signal phosphoprotein, is transcriptionally up-regulated and accumulates in the cytoskeleton/membrane fraction of ICSBP(-/-) BMM. Moreover, our results revealed Dab2 as a novel IFN-gamma-response gene. Both ICSBP and the Ets-transcription factor PU.1 bind to the Dab2 promoter, whereby ICSBP represses PU.1-induced Dab2 promoter transactivation in vitro. Notably, repression of Dab2 expression by ICSBP is also found in myeloid progenitors. Overexpression of Dab2 leads to accelerated cell adhesion and spreading, accompanied by enhanced actin fiber formation. Furthermore, cell adhesion induces transient Dab2 phosphorylation and its translocation to the cytoskeletal/membrane fraction. Our results identify a novel role of Dab2 as an inducer of cell adhesion and spreading, and strongly suggest that the up-regulation of Dab2 contributes to the hematopoietic defect seen in ICSBP(-/-) mice.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Activation of the gene for the PDGF receptor beta1 (PDGFRbeta) in interleukin-3-dependent myeloid cells by retroviral insertional mutagenesis: implications for the transforming potential of PDGFRbeta.

Retroviral insertional mutagenesis has proven to be a powerful tool to identify genetic lesions disrupting normal hematopoiesis. The gene encoding the beta receptor for platelet-derived growth factor (PDGFRbeta) was identified as a target of retroviral mutagenesis in mutants selected for interleukin-3 (IL3)-independent growth. Expression of PDGFRbeta in the parental cells using a retroviral vector increased the frequency of factor-independent growth, confirming the significance of the retroviral integration site. Significantly, however, expression of the receptor did not induce IL3-independent growth in one step. In contrast, TEL-PDGFRbeta, the fusion protein generated by the t(5;12) translocation associated with chronic myelomonocytic leukemia, induced factor-independent growth in all transductants, demonstrating that the TEL-PDGFRbeta fusion protein is a more potent mitogenic signal. Nevertheless PDGFRbeta overexpression is sufficient to give a selective advantage to IL3-dependent cells under adverse conditions, allowing the selection of secondary mutations that impart IL3-independent growth. These results underline the power of insertional mutagenesis to identify subtle but initiating mutations that synergize with other lesions in oncogenic transformation.

3T3 Cells↗
PubMed2002

Hierarchy of stroma-derived factors in supporting growth of stroma-dependent hemopoietic cells: membrane-bound SCF is sufficient to confer stroma competence to epithelial cells.

Hemopoiesis takes place in a microenvironment where hemopoietic cells are closely associated with stroma by various interactions. Stroma coregulates the proliferation and differentiation of hemopoietic cells. Stroma-hemopoietic-cell contact can be supported by locally produced membrane associated growth factors. The stroma derived growth factor, stem cell factor (SCF) is important in hemopoiesis. We examined the different biological interactions of membrane bound and soluble SCF with human hemopoietic cells expressing the SCF receptor, c-kit. To analyze the function of the SCF isoforms in inducing the proliferation of hemopoietic TF1 or Cord blood (CB) CD34+ cells we used stroma cell lines that differ in their presentation of no SCF, membrane SCF, or soluble SCF. We established a new coculture system using an epithelial cell line that excludes potential interfering effects with other known stroma encoded hemopoietic growth factors. We show that soluble SCF, in absence of membrane-bound SCF, inhibits long term clonal growth of primary or established CD34+ hemopoietic cells, whereas membrane-inserted SCF "dominantly" induces long term proliferation of these cells. We demonstrate a hierarchy of these SCF isoforms in the interaction of stroma with hemopoietic TF1 cells. Membrane-bound SCF is "dominant" over soluble SCF, whereas soluble SCF acts epistatically in interacting with hemopoietic cells compared with other stroma derived factors present in SCF deficient stroma. A hierarchy of stroma cell lines can be arranged according to their presentation of membrane SCF or soluble SCF. In our model system, membrane-bound SCF expression is sufficient to confer stroma properties to an epithelial cell line but soluble SCF does not.

Animals↗
PubMed2002

Ethical issues in rehabilitation: a qualitative analysis of dilemmas identified by occupational therapists.

Little available research exists to address the range of ethical issues encountered by occupational therapists (OTs) in their daily clinical work. The few articles in the literature have tended to be case-based or anecdotal or have focused on professional issues rather than clinical issues. To characterize the array of clinical ethical issues in occupational therapy, we asked OTs in a free-standing academic rehabilitation hospital to describe in some detail up to three scenarios or situations from their clinical practice that raised morally troubling questions. A coding system was developed to preserve the richness of the detail but to allow for some categorization of the topics. A second section of the survey asked the therapists to rate whether various traditional ethics topics were of high, medium, or low interest to them. A third section asked that they identify the formats that would be most appealing to them for future educational interventions. Of the 56 therapists surveyed, 38 (or 68%) responded. The three self-generated topics mentioned most frequently by the therapists were (in decreasing order of frequency): reimbursement pressures, conflicts around goal setting, and patient/family refusal of team recommendations. The respondents were particularly interested in knowing more about patient-centered ethics topics, such as conflict resolution between teams and patients and the patient's role in decision making. Furthermore, they indicated a strong preference for interdisciplinary and interactive educational formats.

Journal Article↗