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Biomedical subjects

R Eisma

Publications and source records attributed to R Eisma.

6 recordsLinked to original sources

Characterization of the eosinophil chemokine RANTES in nasal polyps.

Previous studies have demonstrated that the cytokine RANTES (Regulated And Normal T cell Expressed and Secreted) has been shown to be a potent mediator of eosinophil chemotaxis in vitro and of leukocyte recruitment. Because eosinophils are the hallmark cells in nasal polyposis, we hypothesize that RANTES is locally produced within the nasal polyp microenvironment and is responsible for the eosinophil recruitment seen in nasal polyposis. To begin to test this hypothesis, we evaluated nasal polyps from 17 patients and 3 control specimens for distribution and content of RANTES using immunohistochemical techniques and enzyme-linked immunosorbent assay technology. Our immunohistochemical studies demonstrated that in nasal polyposis, RANTES antigen staining occurred predominantly within eosinophils and epithelial cells. To quantify the relative levels of RANTES in normal and nasal polyp specimens, tissue homogenates were prepared, quantified, and normalized to protein levels. We detected RANTES in all 17 nasal polyp tissue homogenates (566 +/- 16 pg/mg total protein). The RANTES levels in nasal polyp homogenates were nearly 40-fold higher than the RANTES levels in normal tissue (15.7 +/- 28.2 pg/mg total protein). Thus, it appears that increased expression of RANTES by eosinophils and epithelial cells within the nasal polyp microenvironment promotes eosinophil recruitment and activation within nasal polyps. We hypothesize that RANTES induces increased recruitment and activation of eosinophils, presumably contributing to the increased tissue changes associated with nasal polyposis.

Adult↗

Expression of basic fibroblast growth factor and its receptors by head and neck squamous carcinoma tumor and vascular endothelial cells.

BACKGROUND: Basic fibroblast growth factor (bFGF) is a potent angiogenic factor implicated in tumor growth and metastasis. To determine if bFGF and basic fibroblast growth factor receptor 1 (bFGFR1) and 2 (bFGFR2) are upregulated in head and neck squamous cell carcinoma (HNSCC), we measured the distribution and levels of each in HNSCC specimens and control specimens. METHODS: Head and neck squamous cell carcinoma and control tissue specimens were analyzed qualitatively (40 patients, 10 controls) using immunohistochemistry, and quantitatively (26 patients, 8 controls) using immunoassays and graded immunohistochemistry. Control tissue consisted of palatal tissue obtained during uvulopalatopharyngoplasty (UPPP). RESULTS: Immunohistochemical analysis revealed that bFGF, bFGFR1, and bFGFR2 antigens were strongly associated with cancer and vascular endothelial cells in HNSCC. Control tissue had moderate staining of vascular endothelium and no stromal staining. Quantitative analysis of bFGF in tissue homogenates indicated that bFGF levels in cancer specimens were significantly elevated compared with control tissues (420.3 +/- 360.9 ng/mg total protein versus 49.2 +/- 48.7, respectively, P < or =0.05). When analyzed by clinical stage, bFGF levels were significantly higher in stage III patients as compared with stage IV patients (P < or =0.01). When immunohistochemistry results were correlated with clinical stage, bFGF (P < or =0.01), bFGFR1 (P < or =0.001), and bFGFR2 (P < or =0.0001) staining was significantly more intense in the cancer cells of stage III versus stage IV patients. CONCLUSION: Enhanced expression of bFGF and bFGF receptors by cancer and vascular endothelial cells is present in HNSCC, and may contribute to tumor growth and metastasis in HNSCC by mediating angiogenesis. Strategies aimed at decreasing the expression of bFGF and its receptors may be of therapeutic benefit in HNSCC, particularly at an early stage of disease.

Carcinoma, Squamous Cell↗

Interleukin-8 expression in human nasal polyps.

The cytokine interleukin 8 (IL-8) has been shown to be a potent mediator of leukocyte recruitment and neovascularization in inflammatory and neoplastic diseases. In this study we hypothesize that IL-8 produced in the nasal polyp microenvironment is responsible for the leukocyte recruitment seen in nasal polyposis. To test this hypothesis we evaluated nasal polyps for distribution and content of IL-8 antigen with immunohistochemical techniques and radioimmunoassay to determine tissue levels of IL-8. The immunohistochemical results demonstrated that IL-8 antigen staining occurred predominantly within inflammatory cells and epithelium. IL-8 was detected in all nasal polyp tissue homogenates (a mean value of 1767 +/- 1633 pg/mg total protein (TP) with a range of 134 to 3668 pg/mg TP vs control specimens with a mean value of 77 pg/mg TP with a range of 0.09 to 255 pg/mg TP). These data demonstrate the presence and distribution and levels of IL-8 antigen in nasal polyps in vivo, supporting our hypothesis that local production of IL-8 could be an important factor in the sustained recruitment of leukocytes in nasal polyposis. Thus IL-8 likely plays a significant role in the pathogenesis of this disease process and therefore is a potential target for therapeutic intervention.

Adult↗

Interferon gamma expression in human nasal polyps.

One feature among nasal polyps (NPs) is the predominance of lymphocytes and eosinophils. We hypothesize that elevated levels of interferon gamma (IFN-gamma) activate lymphocytes and eosinophils within the NP microenvironment. Nasal polyps were evaluated for distribution and levels of IFN-gamma in specimens from 27 patients with nasal polyposis and 4 controls. Immunohistochemical study revealed IFN-gamma staining of eosinophils, glandular cells, and epithelium (27 of 27 patients). ELISA analysis indicated elevated IFN-gamma levels in total NP tissues (25.6 +/- 7.23 pg/mg total protein [TP]) compared with controls (16.27 +/- 6.54 pg/mg TP). Three subpopulations were identified based on IFN-gamma levels: low IFN-gamma group (10.7 +/- 5.51 pg/mg TP); medium IFN-gamma group (25.70 +/- 5.90 pg/mg TP); and high IFN-gamma group (52.58 +/- 10.29 pg/mg TP). The latter levels were approximately 3.5 times the control levels (P<0.0025). Patients with previous polypectomy surgery showed higher levels of IFN-gamma compared with controls (P<0.0423). A trend was found with increased IFN-gamma levels and allergy, asthma, and topical steroid use.

Adult↗

Interleukin-3 interleukin-5, and granulocyte-macrophage colony-stimulating factor expression in nasal polyps.

PURPOSE: Nasal polyps (NP) are grape-like clusters of chronically inflamed tissue. Little is known about the underlying cells and cytokines involved in nasal polyposis. For the present study, we hypothesize that elevated tissue levels of interleukin-3 (IL-3), interleukin-5 (IL-5), and granulocyte-macrophage colony-stimulation factor (GM-CSF) contribute to eosinophil recruitment and activation in NP. MATERIALS AND METHODS: To begin to test this hypothesis, we evaluated IL-3, IL-5, and GM-CSF levels and distributions in nasal polyp specimens obtained intraoperatively from 13 patients and two normal controls. For these studies, nasal polyp levels were determined by enzyme-linked immunosorbent assay (ELISA), and IL-3, IL-5, and GM-CSF distribution was determined by immunohistochemistry. RESULTS: Immunohistochemical staining of the NP indicated that in all 13 patient samples, IL-3, IL-5, and GM-CSF were associated with infiltrating cells, primarily eosinophils, in the NP. Quantitation of IL-3, IL-5, and GM-CSF in NP tissue homogenates indicated that IL-3, IL-5, and GM-CSF levels were evaluated in the NP tissues when compared with control tissues. Additionally, elevation of individual cytokines correlated with previous polypectomy (IL-3), steroid use (IL-3, IL-5, and GM-CSF), asthma (IL-5), and age (GM-CSF). CONCLUSION: These data support our hypothesis that IL-3, IL-5, and GM-CSF are likely to play a key role in eosinophil recruitment/activation and NP formation and support recently advanced theories that cytokines play a key role in the pathogenesis of this disease.

Adult↗

An enzyme-linked immunosorbent assay for urinary screening of fentanyl citrate abuse.

An enzyme-linked immunosorbent assay (ELISA) for quantitation of urinary fentanyl was evaluated as a screening tool for detecting abuse of this potent narcotic. The assay was found to have reproducible calibration curves from 0.5 to 10 ng/mL and a limit of detection of 0.5 ng/mL. Interference by proteins, glucose, or pH was negligible. The assay was specific for fentanyl with little cross-reactivity against despropionyl fentanyl and norfentanyl metabolites, other analgesics and common drugs of abuse. To evaluate its use in humans, urines were collected from 57 normal individuals, 48 patients seen in the Emergency Department, and 18 surgical patients receiving either low (50 micrograms) or moderate fentanyl dosage (200 and 250 micrograms) for routine anesthesia. In patients receiving 50 micrograms (a dose consistent with early abuse), urinary fentanyl was detectable for 3 to 10 h post administration. In patients receiving 200 or 250 micrograms (a dose more consistent with addiction), urinary fentanyl was detectable for longer time periods (> 24 h). These results indicate that the ELISA is sensitive for the detection of recent fentanyl exposure under conditions likely to mimic those in abuse and addiction. The assay is simple to perform, reliable, and can be used to screen urine specimens prior to gas chromatography/mass spectrometry (GC/MS) confirmation.

Calibration↗