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Biomedical subjects

Kristin A Seiberling

Publications and source records attributed to Kristin A Seiberling.

6 recordsLinked to original sources

Chronic rhinosinusitis and superantigens.

This article discusses the potential role of bacterial superantigens (SAgs) in chronic rhinosinusitis with nasal polyposis (CRS/NP). First, it briefly describes SAgs, focusing on how they interact with the immune system by binding to T-cell receptors (TCR) and major histocompatibility complex (MHC) class II molecules. Second, it discusses the role of SAgs in other chronic inflammatory diseases.Finally, it presents evidence for the role of SAgs in the pathogenesis and maintenance of CRS/NP focusing on current research and future considerations.

Chronic Disease↗

Superantigens and chronic rhinosinusitis: detection of staphylococcal exotoxins in nasal polyps.

OBJECTIVE/HYPOTHESIS: The role of infectious agents in the etiology of chronic rhinosinusitis with nasal polyposis (CRSwNP) remains unclear. Recent studies have provided indirect evidence of exposure to staphylococcal exotoxins in the blood and polyp tissue of patients with CRSwNP. These exotoxins have the capacity to act as superantigens, bypassing normal antigen processing and directly stimulating a massive inflammatory response. The objective of the study was to analyze mucus and polyp tissue samples from patients with CRSwNP for the presence of staphylococcal exotoxins. STUDY DESIGN: Prospective study. METHODS: Tissue and mucus samples were obtained from 42 patients undergoing endoscopic sinus surgery for chronic rhinosinusitis and 11 normal control patients. Twenty-nine of 42 patients had chronic rhinosinusitis with bilateral nasal polyposis, 2 had antrochoanal polyps, and 11 had chronic rhinosinusitis without nasal polyps. Eleven patients without chronic rhinosinusitis or polyps served as normal control patients. Specimens were analyzed for the presence of five staphylococcal exotoxins (SEA, SEB, SEC, SED, and toxic shock syndrome toxin type 1 [TSST-1]) using enzyme-linked immunosorbent assay (ELISA). Histological analysis of specimens and mean eosinophil counts were correlated with the presence of toxin. RESULTS: At least one toxin was detected in 14 of 29 patients with bilateral nasal polyposis. Nine of the 14 patients also had positive findings for additional toxins. The dominant histological pattern in the CRSwNP patient group was polypoid mucosa with edema, which was found in both ELISA-positive and ELISA-negative patients. Mean eosinophil counts tended to be higher in ELISA-positive patients with polyps compared with patients without toxin detection. No toxin was detected in the 11 specimens taken from normal control patients. Only 1 of the 13 patients with CRS without polyps had positive ELISA results for toxin. CONCLUSION: The current study demonstrates the presence of superantigen toxins in 14 of 29 patients with CRSwNP, with SEB and TSST-1 being the most common. Further studies are necessary to correlate the presence of toxin with the pathological changes present in polyp tissue.

Adult↗

Aging and olfactory and taste function.

This article focuses on the change in olfaction and taste with aging. It discusses histopathology with an emphasis on age-related changes, causes of chemosensory dysfunction in the elderly, how to evaluate a patient with dysfunction, useful tests and imaging, clinical consequences of chemosensory impairments, and available treatment options.

Aged↗

Role of intrathyroidal calcifications detected on ultrasound as a marker of malignancy.

OBJECTIVES: Clinically palpable thyroid nodules are present in between 4% and 7% of the population, with only a small percentage of those harboring malignancy. Thus, it is important to find a cost-effective way to determine which nodules are more likely to be malignant. The purpose of this study was to evaluate the use of intrathyroidal calcifications detected on ultrasound as a risk factor for malignancy. STUDY DESIGN: Retrospective chart review. METHODS: One hundred fifty-nine patients with thyroid disease were included in this study. Patients were selected from a thyroid ultrasound (TUS) database. Charts were then reviewed, and only those patients who had a preoperative TUS and underwent surgery for tissue diagnosis were included. RESULTS: Of the 159 patients, 66 (41.5%) were diagnosed with cancer. Of those with malignancy, 52 (78.8%) had calcifications noted on TUS. Ninety-three of the patients were diagnosed with benign pathology. Of those 93 patients, 36 (38.7%) had TUS findings consistent with calcifications, whereas 57 (61.3%) did not. Statistical analysis using a chi-square test showed a strong association between cancer status and calcification, with P <.001. In our study, calcifications on TUS had a sensitivity of 78.8% and a specificity of 61.3%, with an odds ratio of 5.88. CONCLUSION: The presence of calcifications detected on TUS should alert the physician for the possibility of malignancy, and further work-up should be pursued. This information may be used to improve the sensitivity of other diagnostic tests such as fine needle aspiration biopsies. Given the relatively low sensitivity and specificity of the test, its use alone as a marker of malignancy is limited, but it may be used in combination with other known risk factors and tests to decide on the most appropriate treatment plan.

Adenocarcinoma, Follicular↗

Superantigens and chronic rhinosinusitis II: analysis of T-cell receptor V beta domains in nasal polyps.

BACKGROUND: The superantigen (SAg) hypothesis of chronic rhinosinusitis (CRS) suggests that toxins within the nose stimulate massive oligoclonal expansion of T-cell populations with subsequent eosinophil recruitment and tissue inflammation. SAgs are capable of activating 1 x 10(4) more lymphocytes than conventional antigens by binding specific Vbeta-domains of the T-cell receptor (TCR). The net effect is skewing from the normal Vbeta-profile by oligoclonal expansion of specific domains. This study will assess polyp tissue for evidence of an SAg response in CRS with nasal polyps (CRSwNP). METHODS: This study consists of a prospective analysis of 18 CRSwNP subjects undergoing sinus surgery. Flow cytometry was used to analyze the distribution of 24 specific TCR V beta-domains in lymphocytes from polyp tissue and blood. Evidence of oligoclonal expansion was tabulated for each specimen and defined as mean normative percentage + 2 SD. RESULTS: Eighteen of 18 CRSwNP subjects showed expansion of polyp lymphocytes expressing TCRs with specific V beta-domains. The average number of V beta-clones per CRSwNP subject was seven in polyp lymphocytes but only two in blood lymphocytes. CONCLUSION: The current results indicate that polyp lymphocytes exhibit significant oligoclonal expansion of specific V beta-domains. These data are considered diagnostic of a SAg effect. The corresponding blood profile is much less, suggesting that the nose is the primary source of stimulus. Although the trigger(s) for this expansion are unknown, these data are consistent with the hypothesis that staphylococcal toxins are central to the development of CRSwNP.

Chronic Disease↗

Superantigens and chronic rhinosinusitis: skewing of T-cell receptor V beta-distributions in polyp-derived CD4+ and CD8+ T cells.

BACKGROUND: Recent studies have suggested that Staphylococcus aureus secrete superantigenic toxins that play a role in the etiology of chronic rhinosinusitis with nasal polyposis (CRSwNP). Twenty S. aureus superantigens (SAg's) have been identified, each of which bind the V beta-region of the T-cell receptor (TCR) outside the peptide-binding site. Approximately 50 distinct V beta-domains exist in the human repertoire, and distinct SAg's will bind only particular domains generating a pattern of V beta-enrichment in lymphocytes dependent on the binding characteristics of a given toxin. The aim of this study was to analyze the pattern of V beta-expression in polyp-derived lymphocytes from CRSwNP patients. METHODS: Polyps were harvested from 20 patients with CRSwNP and 3 patients with antrochoanal polyps. Flow cytometry was used to analyze the V beta-repertoire of polyp-derived CD4+ and CD8+ lymphocytes. Data were analyzed in light of the known skewing associated with SAg exposure in vivo and in vitro. Skewing was defined as a percentage of V beta-expression >2 SD of that seen in normal blood. RESULTS: Seven of 20 subjects exhibited skewing in V beta-domains with strong associations with S. aureus SAg's. The three antrochoanal polyps failed to show any significant V beta-skewing. CONCLUSION: This study establishes evidence of S. aureus SAg-T-cell interactions in polyp lymphocytes of 35% of CRSwNP patients. Although these results are consistent with intranasal exposure of polyp lymphocytes to SAg's, additional study is necessary to establish the role of these toxins in disease pathogenesis.

CD4-Positive T-Lymphocytes↗