RESUMEN
BACKGROUND: Gaucher disease (GD) is the most common autosomal recessive lipid storage disease. In this study, the changes in TFH cells and IL-4 and IL-21 cytokines in blood samples of GD patients, carriers and healthy volunteers were investigated. METHODS: Two pretreatment type 1 GD patients, 20 currently treated type 1 GD patients, 6 carriers, and 27 healthy volunteers were enrolled in the study. TFH cell (CD45RA-CD4+CXCR5+) number, phenotype (PD1, ICOS expression), and cytokine production (IL-21, IL-4) were assessed via flow cytometric assays. RESULTS: No significant differences were found between the groups with respect to the number, frequency and PD1 or ICOS expression of TFH cells between healthy controls, patients and carriers. However, IL-4+ TFH cells were significantly reduced both in percent and number in the treated GD patients compared with healthy controls (p < 0.05). Interestingly, the IL-21+ TFH cell number was increased in treated GD patients. When TFH cells were examined based on CXCR3 expression, the frequency of the PD1+Th17-Th2-like fraction (CXCR3-) was found to be significantly increased in treated GD patients. CONCLUSION: To our knowledge, this is the first study to assess TFH cells in GD patients, and to show that the production of IL-4 and IL-21 by TFH cells and their subsets may be altered in type 1 GD patients.
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Enfermedad de Gaucher , Células T Auxiliares Foliculares , Humanos , Linfocitos T Colaboradores-Inductores/metabolismo , Enfermedad de Gaucher/metabolismo , Interleucina-4 , Interleucinas , Linfocitos T CD4-PositivosRESUMEN
BACKGROUND AND AIMS: Gaucher disease (GD) is caused by a genetic deficiency of the beta-glucocerebrosidase enzyme which results in the accumulation of glucosylceramide in macrophages. This accumulation may induce oxidative stress, resulting in DNA damage in patients with GD. The aim of this study was to assess plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and cytokinesis-block micronucleus cytome (CBMN-cyt) assay parameters in the peripheral blood lymphocytes of patients with GD and carriers, evaluate the possible associations of these values with GD, and determine whether they can be used as potential biomarkers in GD. METHODS: This study included 20 patients with type 1 GD, six carriers, and 27 age- and sex-matched healthy controls. CBMN-cyt assay parameters in peripheral blood lymphocytes of the patients with GD, carriers, and controls were evaluated and 8-OHdG levels in their plasma samples were measured. RESULTS: CBMN-cyt assay parameters in patients with GD and carriers were not significantly different when compared with controls (p > 0.05). However, plasma 8-OHdG levels were found to be higher in both patients with GD and carriers than in control subjects (p < 0.01). CONCLUSIONS: Oxidative DNA damage may be a useful prognostic tool, whereas the CBMN-cyt assay cannot be used as a predictive biomarker of GD.
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Enfermedad de Gaucher , Humanos , Pruebas de Micronúcleos/métodos , Enfermedad de Gaucher/genética , Núcleo Celular/genética , 8-Hidroxi-2'-Desoxicoguanosina , Biomarcadores , Daño del ADN , Linfocitos , Estrés OxidativoRESUMEN
OBJECTIVE: To evaluate the diagnostic value of argyrophilic nucleolar organizing regions (AgNORs) in the nondiagnostic fine needle aspiration biopsy (NFNAB) specimens (due to insufficient cell groups) of cases with thyroid nodules. STUDY DESIGN: Thirty-five patients with NFNAB were included in the study. FNAB stained with Giemsa was faded using the McKee technique, then stained for AgNOR detection according to a specific protocol. One hundred nuclei per individual were evaluated to detect the AgNOR count/nucleus and total AgNOR area/ nuclear area (TNA/NA) of individual cells by using a computer program. RESULTS: The AgNOR values of patients with NFNAB were between 1.2-2.4% for AgNOR count/ nucleus and between 3.1-9.1%for TNA/NA. When the cutoff values were taken as > 3 for AgNOR count/nucleus and > 8 for TNA/NA, the sensitivity ratios were 100% and 97% for AgNOR count/nucleus and TNA/ NA for discriminating benign/malignant lesions. CONCLUSION: By using some cutoff values obtained from a modified AgNOR staining method, benign/malignant potential of thyroid aspirations with NFNAB may be estimated. (Anal Quant Cytopathol Histopathol
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Región Organizadora del Nucléolo/patología , Patología Clínica/métodos , Tinción con Nitrato de Plata/métodos , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/patología , Adulto , Anciano , Biopsia con Aguja Fina/métodos , Núcleo Celular/patología , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Argyrophilic nucleolar organising region associated proteins (AgNORs) are of interest in a variety of diseases including thyroid disorders. We have investigated the cut-off values for AgNOR count and with a new approach, Total AgNOR area/nuclear area (TNORa/Na) proportions to discriminate thyrocytes obtained from benign thyroid nodules and normal thyroid tissue. Thirty patients whose fine needle aspiration (FNA) materials were compatible with a benign lesion (named as goiter group) and 30 controls (subjects with normal thyroid tissue) were included. In the control group, biopsy material was obtained from histologically normal thyroid gland operated on because FNA material was compatible with papillary thyroid carcinoma (PTC). These samples were stained for AgNOR and 100 nuclei per individual were examined. Both AgNOR values for individual cells and cut-off values were detected for each group. Patients with goiter had significantly (P<0.001) higher AgNOR count (2.1 ± 0.6%) and TNORa/Na (6.1 ± 1.5%) than the control groups (1.4 ± 0.2 and 3.0 ± 0.4, respectively). The cut-off values were <1.5 for AgNOR count and <3.8 for TNORa/Na in thyrocytes of the controls. This modified method is an easy and reliable method for discriminating various thyroid disorders, including the differentiation of benign thyroid nodules from malignant ones. It also helps to discriminate thyrocytes obtained from benign nodules from normal thyroid tissue, aiding accurate localisation of sampling in FNA material.
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Antígenos Nucleares/metabolismo , Bocio/metabolismo , Glándula Tiroides/metabolismo , Nódulo Tiroideo/metabolismo , Adulto , Anciano , Biopsia con Aguja Fina , Estudios de Casos y Controles , Tamaño del Núcleo Celular , Femenino , Bocio/patología , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Valores de Referencia , Glándula Tiroides/patología , Nódulo Tiroideo/patologíaRESUMEN
Argyrophilic nucleolar organizing region associated proteins (AgNORs) have been shown to be of interest in a variety of different diseases including thyroid disorders. Our aim was to distinguish benign thyroid lesions from papillary thyroid carcinoma (PTC) via AgNOR count and with a new approach, via AgNOR surface area/total nuclear surface area (NORa/TNa) proportions in the nuclei on fine-needle aspiration (FNA) materials. Thirty patients (eight men and 22 women) whose FNA was compatible with benign lesion and 26 patients (eight men and 18 women) whose FNA was compatible with PTC were included in the study. Fine-needle aspiration materials were stained for AgNOR detection according to a specific protocol. One hundred nuclei per individual have been evaluated, and AgNOR number and NORa/TNa proportions of individual cells were measured and calculated by using a computer program. Patients with PTC had significantly (p<0.001) higher AgNOR count (4.6 ± 1.2%) than in the patients with benign lesions (2.0 ± 0.5%). Additionally, patients with PTC had significantly (p<0.001) higher NORa/TNa (13.4 ± 2.4) than in the patients with benign lesion (5.7 ± 1.0). Modified method of AgNOR staining is an easy and reliable method for evaluating proliferation activity of cells in malignant and benign thyroid lesions and it may contribute to routine cytopathology in inconclusive situations.
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Carcinoma Papilar/diagnóstico , Bocio Nodular/diagnóstico , Región Organizadora del Nucléolo/patología , Glándula Tiroides/patología , Neoplasias de la Tiroides/diagnóstico , Adulto , Biopsia con Aguja Fina , Carcinoma , Carcinoma Papilar/genética , Femenino , Bocio Nodular/genética , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Tinción con Nitrato de Plata , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/genéticaAsunto(s)
Proteína BRCA2/genética , Neoplasias de la Mama/genética , Islas de CpG/genética , Metilación de ADN , Exones/genética , Glándulas Mamarias Humanas/patología , Adulto , Electroforesis en Gel de Agar , Femenino , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas/genéticaRESUMEN
Traditional criterions are not sufficient to predict accurately the recurrence of transitional cell carcinoma of the urinary bladder. Therefore, we aimed to evaluate the AgNORs via total AgNOR area/nucleus area (TAA/NA) for each cell as a prognostic parameter, in TCC of urinary bladder. Tumor tissues of 20 consecutive cases of male bladder cancer patients were divided into two groups as middle differentiated (LG) and high grade (HG). The extra-tumoral tissue (ETT) samples of 10 males served as control group. A second control group (HC) consisted of five healthy and normal bladder tissue samples. The 3 microm of sections from each paraffin embedded tumoral, extra-tumoral and normal tissue samples served as patient and control groups. After deparaffinization and rehydratation steps, silver (AgNO(3)) staining of nucleolar organizer regions-associated proteins (AgNORs) was performed. Instead of Giemsa stain, we used Hematoxylin for contra staining. The images of the 100 analyzable nuclei from each tissue sample, transferred by means of a video camera and video capture card from microscope and recorded onto a computer. Software was prepared in Delphi language for analysis. Mean (E+02) TAA/NA values of HC, ETT, LG and HG groups were 6.97+2.80, 5.70+1.82, 7.80+3.22 and 9.24+3.88, respectively. Statistical comparisons have shown significant differences between all groups. In conclusion, mean TAA/NA per cell has a potential to be a prognostic parameter. Therefore, further evaluation of big patient series will be useful.