Interlaboratory variability of rotational chair test results II: analysis of simulated data.

Standardization of rotational chair testing across laboratories has not been achieved because of differences in test protocol and analysis algorithms. The Interlaboratory Rotational Chair Study Group was formed to investigate these differences. Its first study demonstrated significant variability in calculated results using actual patient data files. No estimation of accuracy could be made, however, because the "true" values of response parameters were unknown. In this study we used simulated "patient" data files to further explore the differences among analysis algorithms. We found a high degree of agreement and accuracy across laboratories using automated analysis of high signal-to-noise/low-artifact data for gain, phase, and asymmetry. Variability increased significantly for the lower signal-to-noise ratio/higher artifact files. Operator intervention generally improved accuracy and decreased variability, but there were cases in which operator intervention reduced accuracy.     

Th-2 type cytokine receptors in allergic rhinitis and in response to topical steroids

Objectives: Th-2 type cytokine production (inter-leukin-4 [IL-4] and interleukin-5 [IL-5]) has been demonstrated to play a significant role in the pathophysiology of allergic rhinitis (AR), and the treatment of AR with topical corticosteroids has been shown to reduce the expression of Th-2 type cytokines in vivo. However, the contribution and expression of Th-2 type cytokine receptors in AR and their response to corticosteroid treatment remain to be clarified. Objectives of the current study are 1. To examine the expression of the cytokine IL-4 and IL-5 receptors (IL-4R and IL-5R) in a nasal allergen challenge model and to contrast this with the expression of the receptor for the Th-1 type cytokine, interferon-gamma receptor (IFN-γR), and 2. to examine the effects of pretreatment with topical corticosteroid before allergen challenge on the expression of these same receptors. Study Design: Randomized prospective study involving 14 ragweed-allergic subjects evenly divided between placebo and corticosteroid pretreatment. Methods: Immunocytochemistry (alkaline phosphatase-antial-kaline phosphatase labeling [APAAP] technique) was used to stain nasal biopsy specimens before and after allergen challenge. Antibodies used included anti-CD3, CD4, CD8, MBP, IL-4R, IL-5R, and IFN-γR. Results: Following allergen challenge, we observed a significant increase in the Th-2 type cytokine receptors (IL-4R and IL-5R; P < .05), as well as a significant decrease in the expression of the Th-1 type cytokine receptor (IFN-γR; P < .05). Pretreatment with topical corticosteroids before nasal allergen challenge resulted in decreased expression of IL-4R (P < .05) and IL-5R (P < .05) and increased expression of IFN-γR (P < .05). Further, IL-4R and IL-5R expression correlated with eosinophil infiltration in the tissues. Conclusions: We have demonstrated that in AR, cytokine receptors for IL-4, IL-5, and IFN-γ follow a similar pattern to their ligands. In addition, pretreatment with topical corticosteroids was shown to alter the cytokine receptor expression pattern from a Th-2 profile more toward a Th-1 profile. Laryngoscope, 108:1528–1533,1998     

The HOPA Gene Dodecamer Duplication Is Not a Significant Etiological Factor in Autism

A recent study has suggested that a dodecamer duplication in the HOPA gene in Xq13 may occur in a significant portion of male patients with autism. We have determined the incidence of this duplication in 202 patients from the South Carolina Autism Study. The incidence of the duplication was not significantly different between patients and controls. Three of the female patients inherited the duplication from nonautistic fathers. In addition, there was no systematic skewing of X inactivation in the female patients with the duplication, or in nonautistic mothers and sisters with the duplication. These findings suggest that the dodecamer duplication in the HOPA gene does not play a significant role in the etiology of autism.     

Comparative study on differential accumulation of PSP toxins between cockle (Acanthocardia tuberculatum) and sweet clam (Callista chione).

At the western Mediterranean coast of Morocco, the cockle (Acanthocardia tuberculatum) contained persistent high levels of paralytic shellfish toxins for several years, while other bivalve molluscs such as sweet clam (Callista chione) from the same vicinity were contaminated seasonally to a much lesser extent. In order to understand the causes of this prolonged contamination, a comparative study on PSP decontamination between sweet clam and cockle was conducted from November 2001 until June 2002. PSP toxicity was analysed by automated pre-column oxidation (Prechromatographic oxidation and LC-FD) in several organs of both species, namely digestive gland, foot, gill, mantle, muscle and siphon for sweet clams. The results showed that cockle sequester PSP toxins preferably in non-visceral organs (Foot, gill and mantle) contrary to sweet clam that sequester them in visceral tissues (digestive gland). The toxin profile of cockle organs indicated dominance of dcSTX, whereas sweet clam tissues contained especially C-toxins. Substantial differences in toxin profile between cockle and sweet clam, from the same area as well as from the composition of PSP toxin producer, Gymnodinium catenatum, confirm the bioconversion of PSP toxins in cockle.     

Erythropoietin and erythropoietin receptor expression in head and neck cancer: relationship to tumor hypoxia.

PURPOSE: Erythropoietin, an oxygen-regulated glycoprotein hormone, is a hematopoietic cytokine that stimulates erythropoiesis by binding to its cellular receptor [erythropoietin receptor (EPOR)]. The recombinant form of human erythropoietin is used to prevent or treat anemia in cancer patients. However, in a recent randomized, placebo-controlled trial involving patients receiving curative radiotherapy for squamous cell carcinoma of the head and neck, erythropoietin treatment was associated with poorer locoregional progression-free survival. The purpose of our study was to determine whether EPOR and its ligand erythropoietin are expressed in primary head and neck cancer. We also investigated the hypothesis that erythropoietin expression in malignant cells may be associated with the presence of tumor hypoxia, an important factor involved in resistance to radiation treatment, tumor aggressiveness, and poor prognosis. EXPERIMENTAL DESIGN: Twenty-one patients received an i.v. infusion of the hypoxia marker pimonidazole hydrochloride before multiple tumor biopsies. Contiguous sections from 74 biopsies were analyzed by immunohistochemistry for EPOR and erythropoietin expression and pimonidazole binding. RESULTS: EPOR expression was present in tumor cells in 97% of the biopsies. Coexpression of erythropoietin was observed in 90% of biopsies. Erythropoietin and pimonidazole adduct staining did not always colocalize within tumors, but there was a significant positive correlation between levels of microregional erythropoietin expression and pimonidazole binding. CONCLUSIONS: The coexpression of erythropoietin and EPOR in tumor cells suggests that erythropoietin may potentially function as an autocrine or paracrine factor in head and neck cancer. The expression of the hypoxia-inducible protein erythropoietin in tumor cells correlates with levels of tumor hypoxia.     

ROLE OF INTERMEDIARY BIOMARKERS IN DETERMINING THE ANTICANCER EFFICACY OF MARINE COMPOUNDS

In the present study, two of the probable an umor marine compounds, manzamine A and sarcophine, were screened using benzo[a]pyrene (BP)-derived DNA adduct formation in MCF-7 cells as intermediary biomarker. Briefly, MCF-7 cells were treated with the compounds for 24 h followed by treatment with BP (0.5 μM). After 24h incubation, cellular DNA was isolated and analyzed for BP-derived DNA adducts by ³²P-postlabeling technique. Manzamine A and sarcophine increased the BP-DNA adducts by 2 to 4-folds. Further, manzamine A (50 μM) substantially down regulated the expression of p53 while sarcophine (50 μM) slightly induced the level of p21. The residual DNA repair ability was almost completely abolished by manzamine A while sarcophine was ineffective. Based on our preliminary results, these compounds may be classified as potential genotoxic.     

Localized conjunctival extra-nodal marginal zone B cell lymphoma with presumed paraproteinic crystalline keratopathy

Crystalline corneal deposits have been well reported in individual cases of lymphoproliferative disorders associated with hyper-gammaglobulinemia, hence called ‘Crystalline Paraproteinemic Keratopathy’. This is the first report of corneal deposits in a case of localised conjunctival B-cell Lymphoma without paraproteinaemia/hyper-gammaglobulinemia, hence called ‘Presumed Paraproteinic Crystalline Keratopathy’.