PubMed Health⌕ Search

Biomedical subjects

Kevin High

Publications and source records attributed to Kevin High.

9 recordsLinked to original sources
PubMed2005

5-Oxo-ETE analogs and the proliferation of cancer cells.

MDA-MB-231, MCF7, and SKOV3 cancer cells, but not HEK-293 cells, expressed mRNA for the leukocyte G protein-coupled 5-oxo-eicosatetraenoate (ETE) OXE receptor. 5-Oxo-ETE, 5-oxo-15-OH-ETE, and 5-HETE stimulated the cancer cell lines but not HEK-293 cells to mount pertussis toxin-sensitive proliferation responses. Their potencies in eliciting this response were similar to their known potencies in activating leukocytes and OXE receptor-transfected cells. However, high concentrations of 5-oxo-ETE and 5-oxo-15-OH-ETE, but not 5-HETE, arrested growth and caused apoptosis in all four cell lines; these responses were pertussis toxin-resistant. The same high concentrations of the oxo-ETEs but again not 5-HETE also activated peroxisome proliferator-activated receptor (PPAR)-gamma. Pharmacological studies indicated that this activation did not mediate their effects on proliferation. These results are the first to implicate the OXE receptor in malignant cell growth and to show that 5-oxo-ETEs activate cell death programs as well as PPARgamma independently of this receptor.

Anilides↗
PubMed2005

The effect of malnutrition on risk and outcome of community-acquired pneumonia.

There are many potential mechanisms by which nutritional deficiencies can predispose to an increased risk and worse outcome for CAP. The elderly population is particularly vulnerable. There is a relative lack of data on the effect of nutrition on risk and outcome of CAP. More research is needed to better delineate the impact of nutrition on risk and outcome of CAP.

Adult↗
PubMed2005

A new paradigm for clinical investigation of infectious syndromes in older adults: assessing functional status as a risk factor and outcome measure.

Adults aged 65 and over comprise the fastest growing segment of the U.S. population, and older adults experience greater morbidity and mortality due to infection than young adults. While this factor is well established, most clinical investigation of infectious diseases in the aged focuses on microbiology, and crude endpoints of clinical success such as cure rates or mortality, but often fails to assess functional status, a critical variable in geriatric care. Functional status can be evaluated as a risk factor for infectious disease or an outcome of interest following specific interventions utilizing well-validated instruments. This paper outlines the currently available data suggesting a link between infection, immunity and impaired functional status in the elderly, summarizes commonly employed instruments used to determine specific aspects of functional status, and provides recommendations for a new paradigm in which clinical trials of older adults include functional assessment.

Activities of Daily Living↗
PubMed2004

Differential outcomes of human cytomegalovirus infection in primitive hematopoietic cell subpopulations.

The cellular reservoir for latent human cytomegalovirus (HCMV) in the hematopoietic compartment, and the mechanisms governing a latent infection and reactivation from latency are unknown. Previous work has demonstrated that HCMV infects CD34+ progenitors and expresses a limited subset of viral genes. The outcome of HCMV infection may depend on the cell subpopulations infected within the heterogeneous CD34+ compartment. We compared HCMV infection in well-defined CD34+ cell subpopulations. HCMV infection inhibited hematopoietic colony formation from CD34+/CD38- but not CD34+/c-kit+ cells. CD34+/CD38- cells transiently expressed a large subset of HCMV genes that were not expressed in CD34+/c-kit+ cells or cells expressing more mature cell surface phenotypes. Although viral genomes were present in infected cells, viral gene expression was undetectable by 10 days after infection. Importantly, viral replication could be reactivated by coculture with permissive fibroblasts only from the CD34+/CD38- population. Strikingly, a subpopulation of CD34+/CD38- cells expressing a stem cell phenotype (lineage-/Thy-1+) supported a productive HCMV infection. These studies demonstrate that the outcome of HCMV infection in the hematopoietic compartment is dependent on the nature of the cell subpopulations infected and that CD34+/CD38- cells support an HCMV infection with the hallmarks of latency.

ADP-ribosyl Cyclase↗
PubMed2002

Human cytomegalovirus gene expression during infection of primary hematopoietic progenitor cells: a model for latency.

Human cytomegalovirus (HCMV) resides latently in hematopoietic cells of the bone marrow. Although viral genomes can be found in CD14+ monocytes and CD34+ progenitor cells, the primary reservoir for latent cytomegalovirus is unknown. We analyzed human hematopoietic subpopulations infected in vitro with a recombinant virus that expresses a green fluorescent protein marker gene. Although many hematopoietic cell subsets were infected in vitro, CD14+ monocytes and various CD34+ subpopulations were infected with the greatest efficiency. We have developed an in vitro system in which to study HCMV infection and latency in CD34+ cells cultured with irradiated stromal cells. Marker gene expression was substantially reduced by 4 days postinfection, and infectious virus was not made during the culture period. However, viral DNA sequences were maintained in infected CD34+ cells for >20 days in culture, and, importantly, virus replication could be reactivated by coculture with human fibroblasts. Using an HCMV gene array, we examined HCMV gene expression in CD34+ cells. The pattern of viral gene expression was distinct from that observed during productive or nonproductive infections. Some of these expressed viral genes may function in latency and are targets for further analysis. Altered gene expression in hematopoietic progenitors may be indicative of the nature and outcome of HCMV infection.

Antigens, CD34↗