PubMed Health⌕ Search

Biomedical subjects

Poupak Fallahi

Publications and source records attributed to Poupak Fallahi.

At least 19 recordsLinked to original sources
PubMed2006

Induction of chromatid-type aberrations in peripheral lymphocytes of hospital workers exposed to very low doses of radiation.

Radiological personnel represent workers exposed to low cumulative doses of radiation. As their surveillance is generally based on physical dosimetry, there is little or inconclusive information on biological effects due to radiation exposure at these doses. We aimed to explore the extent of chromosomal damage in circulating lymphocytes of hospital workers (technicians, nurses and physicians) chronically exposed to a very low level of radiation using conventional and molecular cytogenetic analyses (chromosome painting with chromosomes #2, #3 and #10 as probe cocktail). Compared with controls, exposed workers displayed a significant increase in the frequency of aberrant lymphocytes (1.26+/-0.11/100 cells versus 1.63+/-0.17/100 cells). In particular, exposed technicians showed significantly higher mean values than nurses or physicians (3.68+/-1.17/100 cells versus 1.36+/-0.18/100 cells and 1.36+/-0.09/100 cells, respectively). Interestingly, we found that the chromosomal damage was prevalently expressed as chromatid-type aberrations. Chromosome painting indicated that the frequency of chromosome rearrangements (CR; translocations and dicentrics pooled together) was approximately comparable between radiological workers and the control group. Moreover, we did not detect any significant difference due to radiation exposure when CR rates were considered separately for each of the three chromosomes in the probe cocktail.

Chromatids↗
PubMed2006

Analysis of chromosome damage in circulating lymphocytes of radiological workers affected by thyroid nodules.

The aim of our study was to assess whether or not thyroid nodularity in combination with occupational exposure to low levels of ionising radiation would be correlated with chromosome damage in peripheral lymphocytes. Conventional chromosome-aberration analysis was performed on a group of 92 hospital workers with or without thyroid nodules. On the basis of measurements of their exposure levels, the workers were classified into a low (mean total level=0.03 mSv), medium (mean total level=1.04 mSv) or high (mean total level=8.60 mSv) exposure category. Our results indicate that among workers with thyroid nodules, the high-exposed workers showed significantly higher levels of both total (2.35+/-0.34 per 100 cells) and chromosome-type aberrations (1.46+/-0.20 per 100 cells) than medium-exposed (0.98+/-0.42 and 0.68+/-0.25 per 100 cells, respectively) or low-exposed workers (1.11+/-0.29 and 0.58+/-0.17 per 100 cells, respectively). Workers without thyroid nodules had comparable frequencies of chromosome aberrations among the three exposure categories. To our knowledge, this is the first study revealing a slight, but significant increase of chromosome damage in peripheral lymphocytes from hospital workers who developed thyroid nodules under conditions of occupational exposure to radiation well below the threshold limit for the workplace. The existence of a possible association between chromosome aberrations and development of thyroid nodularity will be discussed.

Analysis of Variance↗
PubMed2006

Increase of CXC chemokine CXCL10 and CC chemokine CCL2 serum levels in normal ageing.

No study has evaluated contemporaneously serum CXC and CC chemokines changes in normal ageing. Serum levels of CXCL10 (sCXCL10) (CXC) and CCL2 (sCCL2) (CC) prototype chemokines have been measured in 164 healthy subjects, from 10 to 79 years of age (82 males/82 females). By simple regression analysis, sCXCL10 and sCCL2 were significantly related with increasing age (r=0.32, p<0.001; r=0.31, p<0.0001, respectively), and with each other (r=0.30, p=0.0004). In a multiple linear regression model, only age and sCCL2 were significantly related to sCXCL10 levels (p<0.001); age and sCXCL10 were significantly related to sCCL2 levels (p<0.001). Subjects with high sCXCL10 levels (>150 pg/ml) were not significantly associated with those with high sCCL2 levels (>559 pg/ml). This study, performed in healthy subjects on an age gradient, demonstrates an increase of sCXCL10 and sCCL2 with advancing age; the differential increase of sCXCL10 or sCCL2 may reflect a general shift towards Th1 or Th2 cytokines pattern, respectively.

Adolescent↗
PubMed2006

Thyroid disorders in chronic hepatitis C virus infection.

The prevalence of thyroid disorders has been evaluated in patients with hepatitis C virus (HCV) infection by many studies. From a review of the published controlled studies, it is possible to observe that: (1) most investigated patients with chronic HCV hepatitis, while a minority evaluated hepatitis C virus antibody (HCVAb)- seropositive patients (the two conditions are not comparable with regards to thyroidal repercussions, in fact, HCVAb-seropositive patients do not necessarily display changes of the immune system present in chronically infected HCV patients); and (2) some authors selected as internal control hepatitis B virus (HBV)-infected patients, while others selected apparently healthy controls or HCVAb-negative subjects. Pooling all data about HCV-positive patients (with chronic hepatitis or HCVAb positivity) and using as control the sum of healthy controls, HBV-infected patients and sera negative for HCVAb, a significant increase of the prevalence has been observed both for thyroid autoimmune disorders (odds ratio [OR] = 1.6; 95% confidence interval = [C]) 1.4-1.9) as well as for hypothyroidism (OR = 2.9; 95% CI = 2.0-4.1). The results of the epidemiologic studies showing an association between HCV infection and thyroid cancer need to be confirmed. The abovementioned evidences seem sufficient to suggest careful thyroid monitoring during the follow-up of patients with HCV infection.

Autoimmune Diseases↗
PubMed2006

Increase of interferon-gamma-inducible CXC chemokine CXCL10 serum levels in patients with active Graves' disease, and modulation by methimazole therapy.

BACKGROUND: CXCL10 plays an important role in the initial phases of Graves' disease (GD) and autoimmune thyroiditis (AT); however, until now, CXCL10 serum levels (sCXCL10) in patients with GD have never been evaluated in relation to thyroid function and treatment. OBJECTIVE: To evaluate sCXCL10 in GD. DESIGN: Cross-sectional. PATIENTS: One hundred and three GD, 164 AT, 20 nontoxic multinodular goitre (NTMNG), 16 toxic nodular goitre (TNG) patients and 70 healthy controls (age- and sex-matched). MEASUREMENTS: We measured sCXCL10 in patients and controls, to relate this parameter to the clinical phenotype. RESULTS: Mean sCXCL10 in GD and AT patients were comparable (122+/-81 and 133+/-102 pg/ml) and significantly higher (P<0.01) than in controls or NTMNG patients (73+/- 32 and 76+/- 25 pg/ml, respectively). Hyperthyroid GD had significantly higher sCXCL10 than euthyroid or hypothyroid GD (145+/- 92, 107+/- 56 and 105+/- 46 pg/ml, respectively; P=0.01). GD patients with untreated hyperthyroidism had higher sCXCL10 than hyperthyroid or euthyroid GD patients under methimazole (MMI) treatment (166+/-125, 124+/- 41 and 94+/- 35 pg/ml, respectively; P=0.006). Comparable sCXCL10 levels were observed in newly diagnosed untreated hyperthyroid GD patients with respect to untreated patients with relapse of hyperthyroidism after a previous MMI course (176+/-125, 155+/- 97 pg/ml, respectively). GD had similar sCXCL10 to AT and higher than TNG patients or controls (all age- and sex-matched) (144+/- 81, 149+/- 114, 101+/- 27 and 86+/- 44 pg/ml, respectively; P=0.02). CONCLUSIONS: sCXCL10 is associated with the active phase of GD in both newly diagnosed and relapsing hyperthyroid patients. The reduction in sCXCL10 in treated patients with GD may be related to the immunomodulatory effects of MMI.

Adult↗
PubMed2006

Prevalence of hypothyroidism and Graves disease in sarcoidosis.

BACKGROUND: The association of sarcoidosis (S) and thyroid autoimmunity has been reported by several studies in a wide range of variability. The aim of our study was to evaluate the prevalence of clinical and subclinical thyroid disorders in patients with S vs gender-matched and age-matched control subjects. METHODS: Thyroid hormones and antithyroid antibodies, thyroid ultrasonography and fine-needle aspiration were performed in 111 patients with S who had been consecutively referred to the Respiratory Pathophysiology Section of the University of Pisa, and the results were compared to 333 gender-matched and age-matched control subjects from the same geographic area. RESULTS: The odds ratio for subclinical hypothyroidism for female patients with S vs control subjects was 2.7 (95% confidence interval [CI], 1.3 to 5.9); for anti-thyroid peroxidase antibody titer (AbTPO) positivity, 2.2 (95% CI, 1.2 to 3.9); and for thyroid autoimmunity, 1.9 (95% CI, 1.1 to 3.2). The mean values of thyroid-stimulating hormone and AbTPO were higher in female S patients than in control subjects (p < 0.01). A significantly higher prevalence of clinical hypothyroidism (four patients) and Graves disease (three patients) was observed in female S patients than in control subjects (none; p = 0.005 and 0.0026, respectively). Two cases of papillary thyroid cancer were detected in S patients. No significant difference between S patients and control subjects was detected for free triiodothyronine and thyroxine, antithyroglobulin autoantibodies, thyroid volume and nodularity, and subclinical hyperthyroidism. CONCLUSIONS: Thyroid function, AbTPO antibodies, and ultrasonography should be tested as part of the clinical profile in female S patients. Subjects who are at high risk (female subjects, those with positive AbTPOs, and those with hypoechoic and small thyroid) should have thyroid function follow-up and appropriate treatment in due course.

Age Distribution↗
PubMed2006

Increased serum CXCL10 in Graves' disease or autoimmune thyroiditis is not associated with hyper- or hypothyroidism per se, but is specifically sustained by the autoimmune, inflammatory process.

OBJECTIVE: Serum CXCL10 (an interferon-gamma-inducible chemokine) levels (sCXCL10) are increased in several autoimmune conditions, including Graves' disease (GD) and autoimmune thyroiditis (AT). Longitudinal assessment of sCXCL10 in autoimmune hypo- or hyperthyroidism has not yet been performed. DESIGN AND METHODS: We longitudinally assayed sCXCL10 in the following groups: thirty-three GD and 11 toxic nodular goiter (TNG) patients when hyperthyroid (Hyper) and when reaching euthyroidism (Eu) with methimazole therapy (MMI) sixty-six AT (33 hypothyroid (Hypo) and 33 Eu) patients, basally and after reaching EU (for Hypo) with levothyroxine (L-T4) therapy twenty-two patients with thyroid cancer (CA) under L-T4-suppressive treatment, of whom 11 were re-evaluated after L-T4 withdrawal for diagnostic WBS, and 11 after recombinant TSH (rhTSH) administration thirty-three healthy controls. RESULTS: At initial evaluation, Hyper GD and AT (Hypo significantly higher than Eu) showed significantly higher mean sCXCL10 than all other groups. MMI treatment led to a significant decrease in sCXCL10 only in GD (not in TNG), while restoration of Eu, in Hypo AT, by L-T4 was not accompanied by significant sCXCL10 change. CA showed sCXCL10 comparable to controls, and both Hypo after L-T4 withdrawal and rhTSH injection had no effect on sCXCL10. CONCLUSIONS: Treatment of Hyper leads to a significant decrease in sCXCL10 only in GD, and this probably depends upon the MMI immunomodulatory effect. L-T4 correction of Hypo is not accompanied by significant modification of sCXCL10 in AT. Increased sCXCL10 is not associated with Hyper or Hypo per se, but is specifically sustained by the autoimmune inflammatory event occurring in both GD and AT.

Adult↗
PubMed2006

High prevalence of thyroid autoimmunity and hypothyroidism in patients with psoriatic arthritis.

OBJECTIVE: To evaluate the prevalence of thyroid disorders in a group of patients with psoriatic arthritis (PsA). METHODS: A complete thyroid investigation was carried out in 80 patients with PsA, in gender- and age-matched subjects (1:5) drawn from the general population (controls), and in 112 patients with rheumatoid arthrtitis (RA) with similar iodine intake. RESULTS: Anti-thyroid peroxidase antibodies (AbTPO), a hypoechoic thyroid, and subclinical hypothyroidism were significantly more frequent in women with PsA than in control women, and their frequency was similar to that in patients with RA (positive AbTPO titer 28%, 12%, and 31%; hypoechoic thyroid 31%, 16%, and 36%; subclinical hypothyroidism 25%, 8%, and 12%, respectively). Among men, positive AbTPO titers and a hypoechoic thyroid were found more frequently in the patients with PsA and RA than in controls (positive AbTPO titer 14%, 5%, and 2%; hypoechoic thyroid 16%, 10%, and 3%, respectively). All patients with PsA with subclinical hypothyroidism had polyarticular involvement (p </= 0.05) and a longer disease duration (years 19 +/- 15 vs 11 +/- 8, p = 0.03) than patients with euthyroid PsA. The prevalence of subclinical hyperthyroidism, thyroid nodules, and thyroid enlargement was not significantly different among the 3 groups. CONCLUSION: Our results demonstrate a significantly higher prevalence of thyroid autoimmunity (positive AbTPO, hyoechoic thyroid) findings in men and women with PsA and of subclinical hypothyroidism in women with PsA than in the general population. Therefore, thyroid function tests, an AbTPO assay, and thyroid ultrasound should be performed as part of the clinical evaluation, particularly in women with PsA.

Adult↗
PubMed2005

Interferon-gamma-inducible alpha-chemokine CXCL10 involvement in Graves' ophthalmopathy: modulation by peroxisome proliferator-activated receptor-gamma agonists.

CONTEXT: CXC alpha-chemokine CXCL10/inducing protein-10 play an important role in the initial phases of autoimmune thyroid disorders. Human thyrocytes in primary culture produce large amounts of CXCL10 when stimulated by interferon-gamma (IFNgamma) and TNFalpha. OBJECTIVE: Serum CXCL10 levels (sCXCL10) were measured in patients with active or inactive Graves' ophthalmopathy (GO). The effects of IFNgamma and TNFalpha stimulation and peroxisome proliferator-activated receptor-gamma (PPARgamma) activation on CXCL10 secretion in primary cultures of thyrocytes, orbital fibroblasts, and preadipocytes were tested. PATIENTS: Sixty consecutive patients with Graves' disease, 60 age- and sex-matched patients with GO, and 60 controls were studied. RESULTS: sCXCL10 was higher (P < 0.0001) in Graves' disease (120 +/- 83 pg/ml; n = 60) and GO (122 +/- 71; n = 60) patients than in age- and sex-matched euthyroid controls (72 +/- 32; n = 60). Among GO patients, sCXCL10 levels were significantly higher in those (n = 14) with active disease (171 +/- 197) than in those with inactive disease (114 +/- 45 pg/ml; P < 0.003). In primary cultures of thyrocytes, retrobulbar fibroblasts and retrobulbar preadipocytes from GO patients, CXCL10 production was absent under basal conditions; dose-dependent secretion of CXCL10 was not induced by TNFalpha alone, whereas stimulation with IFNgamma or TNFalpha plus IFNgamma induced CXCL10 release. Treatment of all cell types with the PPARgamma agonist, rosiglitazone, dose-dependently (0.1-10 microm) suppressed IFNgamma- plus TNFalpha-induced CXCL10 release. CONCLUSIONS: We conclude that in GO, thyrocytes and retrobulbar cell types participate in the self-perpetuation of inflammation by releasing chemokines under the influence of cytokines. PPARgamma activation plays an inhibitory role in this process.

Adult↗
PubMed2005

Age-dependent changes in CXC chemokine ligand 10 serum levels in euthyroid subjects.

Circulating levels of cytokines are deeply influenced by aging, and few data about serum chemokines are available. The aim of this study was to evaluate the influence of aging on circulating CXCL10. One hundred forty healthy subjects (70 males and 70 females), 10-79 years of age, underwent fasting plasma glucose, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, and CXCL8 serum assay. Thyroid hormone testing for thyroid-stimulating hormone (TSH), antithyroglobulin (AbTg), and antithyroperoxidase (AbTPO) autoantibodies and thyroid ultrasonography were performed in all subjects to exclude the presence of clinical or subclinical thyroid disease. Serum CXCL10 levels were assayed in all subjects and found to be increased in 14 of 70 females (20%) and in 4 of 70 males (5.7%) (p = 0.01). In a multiple linear regression model including age, body mass index (BMI), systolic and diastolic blood pressure, glycemia, total cholesterol, HDL, LDL, triglycerides, TSH, AbTPO, AbTg, and CXCL8, only age was significantly related to CXCL10 [C.R. 1.30 (0.28-2.33), p = 0.001]. No relationship was present between CXCL8 serum levels and age, suggesting a specificity of CXCL10 elevation as a function of age. Results of this study, performed in healthy subjects on an age gradient, demonstrate an increase in serum CXCL10 with advancing age overall in females, supporting the hypothesis of enhanced Th1 immune responses in aging.

Adolescent↗
PubMed2005

Increase of interferon-gamma inducible alpha chemokine CXCL10 but not beta chemokine CCL2 serum levels in chronic autoimmune thyroiditis.

OBJECTIVE: To measure serum levels of CXCL10 and CCL2 prototype chemokines of the two major subclass (CXC and CC) in patients with newly diagnosed chronic autoimmune thyroiditis (AT), and relate the findings to the clinical phenotype. DESIGN AND METHODS: Serum CXCL10 and CCL2 were assayed in 70 consecutive patients with newly diagnosed chronic AT, in sex- and age-matched healthy volunteers (n = 37) and in 20 patients with non-toxic multinodular goiter, extracted from a random sample of the general population from the same geographic area. RESULTS: CXCL10 serum levels were significantly higher in patients with thyroiditis than in controls or multinodular goiter patients, while comparable CCL2 levels were found between groups. CXCL10 levels were significantly increased in hypothyroid patients and in those with an hypoechoic pattern (P = 0.0004 and P = 0.0001, respectively) while serum CCL2 levels were significantly increased in patients older than 50 years and in those with hypothyroidism (P = 0.0001 and P = 0.03, respectively). No correlation between CXCL10 and CCL2 serum levels could be demonstrated. CXCL10 and CCL2 were studied separately in relation to clinical features of AT patients. Two separate multiple linear regression models for CXCL10 and CCL2 were performed, including age, thyroid volume, thyroid stimulating hormone (TSH), FT4, anti-thyroid peroxidase (AbTPO), hypoechoic pattern, and the presence of hypervascularity, demonstrating that ln of serum CXCL10 levels was associated with TSH independently of other possible confounders levels [regression coefficient (R.C.) 0.143 confidence interval (C.I.) (0.042-0.245); P = 0.0059], while serum CCL2 were significantly associated only with age [R.C. 5.412 C.I. (3.838-6.986); P < 0.0001]. CONCLUSION: Our results, obtained in a large cohort of newly diagnosed AT patients demonstrate increased CXCL10 especially in hypothyroid patients with a more aggressive disorder, and normal CCL2 serum levels in AT.

Adult↗
PubMed2004

Thyroid disorders in chronic hepatitis C.

PURPOSE: To explore the association of hepatitis C virus (HCV) infection with thyroid disorders. METHODS: We investigated the prevalence of thyroid disorders in 630 consecutive patients with chronic hepatitis due to HCV infection; all patients were free of cirrhosis and hepatocarcinoma, and were not on interferon treatment. Also included were a control group of 389 subjects from an iodine-deficient area, another control group of 268 persons living in an area of iodine sufficiency, and 86 patients >40 years of age with chronic hepatitis B. Levels of thyroid-stimulating hormone (TSH), free thyroxine (T(4)), and triiodothyronine (T(3)), as well as anti-thyroglobulin and anti-thyroid peroxidase antibodies, were measured. RESULTS: Mean TSH levels were higher (P = 0.001), and free T(3) and free T(4) levels were lower (P <0.0001), in patients with chronic hepatitis C than in all other groups. Patients with chronic hepatitis C were more likely to have hypothyroidism (13% [n = 82]), anti-thyroglobulin antibodies (17% [n = 108]), and anti-thyroid peroxidase antibodies (21% [n = 132]) than were any of the other groups. CONCLUSION: Both hypothyroidism and thyroid autoimmunity are more common in patients with chronic hepatitis C-even in the absence of cirrhosis, hepatocellular carcinoma, or interferon treatment-than in normal controls or those with chronic hepatitis B infection.

Adult↗
PubMed2004

High levels of circulating CXC chemokine ligand 10 are associated with chronic autoimmune thyroiditis and hypothyroidism.

CXC chemokine ligand 10 (CXCL10), an interferon-gamma-inducible chemokine associated with Th1-mediated immune responses, has been proposed as a marker of inflammation in autoimmune diseases. We measured serum CXCL10 concentrations in 223 consecutive patients with newly diagnosed autoimmune thyroiditis (AT), 97 euthyroid controls, and 29 patients with nontoxic multinodular goiter and related this parameter to the clinical phenotype. The three groups were similar in gender distribution and age; among the AT patients, 24% had subclinical hypothyroidism. Serum CXCL10 level was significantly higher in AT patients (157 +/- 139 pg/ml) than in controls (79 +/- 38) or patients with multinodular goiter (90 +/- 32; P < 0.0001). Among patients with AT, CXCL10 levels were significantly higher in those with a hypoechoic ultrasonographic pattern and hypothyroidism. In a multiple linear regression model including age, thyroid volume, hypoechogenicity, hypervascularity, TSH, free T(4), and antithyroid peroxidase, only age (standardized coefficient = 0.39; P = 0.0001) and TSH (standardized coefficient = 0.41; P < 0.0002) were significantly related to serum CXCL10 levels. We conclude that circulating CXCL10 is increased in patients with AT and is associated with hypothyroidism. CXCL10 may be regarded as a marker of a more aggressive thyroiditis leading to thyroid destruction.

Adult↗
PubMed2004

Effect of PPAR-gamma activation and inhibition on glucose-stimulated insulin release in INS-1e cells.

Peroxisome proliferator-activated receptor (PPAR)-gamma is expressed in human beta-cells and in the rat beta-cell line INS-1. Previous studies have suggested that PPAR-gamma agonism (e.g., thiazolidinediones) enhances glucose-stimulated insulin secretion (GSIS) from islets or INS-1 cells. We tested the direct effect on insulin release by INS-1e of a PPAR-gamma agonist (Ro4389679-000-001 at 0.2 and 0.4 micromol/l) and a PPAR-gamma antagonist (SR202 at 0.2 and 0.4 mmol/l). Cells were incubated in 11 mmol/l glucose for 96 h and then challenged with 3.3, 7.5, 11.0, and 20.0 mmol/l glucose for 1 h. Under these control conditions, insulin concentrations in the medium rose from 19 +/- 4 ng/ml (mean +/- SE) to 82 +/- 5, 107 +/- 11, and 103 +/- 10 ng/ml (P <0.0001 by ANOVA). Preincubation for 48 h with the PPAR-gamma agonist potentiated GSIS (to 154 +/- 14 and 156 +/- 12 ng/ml at 20 mmol/l glucose, P <0.01). Cell insulin content was not altered by either acute glucose challenge or PPAR-gamma agonist coincubation. Preincubation for 48 h with SR202 at the higher dose caused a 30% inhibition of GSIS, with no change in cell insulin contents. When cells were preincubated with 11 mmol/l glucose plus 1 mmol/l oleate, GSIS was significantly potentiated (by 30%, P <0.0001); adding Ro4389679-000-001 or SR202 to these preincubations reduced GSIS to the respective levels seen in the absence of oleate (P <0.0001 for both effects). In conclusion, INS-1e cells display a PPAR-gamma tone that is symmetrically modulated and competitively stimulated by oleate.

Animals↗
PubMed2003

Role of neck ultrasonography in the follow-up of children operated on for thyroid papillary cancer.

The aim of this study was to evaluate the role of neck ultrasonography compared to (131)I whole-body scan (WBS) and circulating thyroglobulin (Tg) measurement after thyroid hormone withdrawal in the follow-up of children with thyroid papillary cancer, who had previously undergone total thyroidectomy for the diagnosis of neck lymph node metastases (LNM). Forty-five children were examined. Neck ultrasonography and diagnostic WBS were conclusive about the presence or absence of LNM in 35 patients. Diagnostic WBS revealed the presence of LNM in 6 cases not detected by neck ultrasonography; neck ultrasonography was positive in 3 cases that were negative at diagnostic WBS but confirmed by post-(131)I therapy WBS. One patient with suspicious neck lymphnodes at neck ultrasonography not confirmed by WBS was considered as a false-positive result of neck ultrasonography. Neck ultrasonography and thyroglobulin (Tg) were conclusive about the presence or absence of LNM in 29 patients. Tg was elevated in 10 subjects with negative neck ultrasonography (7 had also lung and/or mediastinic LNM). Tg was undetectable in 5 patients in whom the presence of LNM was confirmed by neck ultrasonography and WBS. In conclusion, our study in children demonstrates that neck ultrasonography can detect LNM that are not suspected by palpation, diagnostic WBS, or serum Tg determination. Furthermore, neck ultrasonography can pinpoint the anatomic site of the LNM.

Adolescent↗
PubMed2002

Prolonged in vitro exposure to autoantibodies against CD38 impairs the function and survival of human pancreatic islets.

Autoantibodies against CD38 (adenosine-5'-diphosphate[ADP]-ribosyl cyclase/cyclic ADP-ribose hydrolase) have been described in 10-12% of patients with type 2 diabetes. In human islets, anti-CD38 autoantibodies (CD38Abs) acutely stimulate insulin release (IR) and increase the cytosolic calcium concentration ([Ca(2+)](i)). Whether CD38Abs affect human islet cell function and survival upon prolonged in vitro exposure is not known. We cultured human islets for up to 7 days in the presence of sera from 10 patients with type 2 diabetes that had neither CD38Ab- nor [Ca(2+)](i)-mobilizing activity (-/-), sera from 6 patients with type 2 diabetes that was CD38Ab-positive and had [Ca(2+)](i)-mobilizing activity (+/+), or no sera (control). At baseline, +/+ sera caused a significant (P < 0.002) acute stimulation of IR (IR at 3.3 mmol/l glucose was 45 +/- 19, 84 +/- 24, and 34 +/- 12 micro U/ml in control, +/+, and -/- sera, respectively; the corresponding IR at 16.7 mmol/l glucose was 72 +/- 25, 204 +/- 56, and 80 +/- 32 micro U/ml). At 3 days, IR at 3.3 mmol/l glucose was 42 +/- 18, 27 +/- 11, and 43 +/- 24 micro U/ml (P = 0.0003) for control, +/+, and -/- sera, respectively, whereas at 16.7 mmol/l glucose, it was 95 +/- 76, 45 +/- 35, and 76 +/- 42 micro U/ml, respectively. After 7 days of exposure, the corresponding IR at 3.3 mmol/l glucose was 40 +/- 11, 28 +/- 12, and 35 +/- 15 micro U/ml, respectively, whereas at 16.7 mmol/l glucose it was 79 +/- 39, 39 +/- 17, and 62 +/- 39 micro U/ml. At both 3 and 7 days, IR still increased when switching from 3.3 to 16.7 mmol/l glucose (P < 0.0003), and incubation with +/+ sera induced a significant decrease in the insulin response (P < 0.002). At 7 days, the number of dead cells (as evaluated by an enzyme-linked immunosorbent assay technique) differed significantly between control (1.2 +/- 0.3 OD units) cells, islets exposed to -/- sera (1.4 +/- 0.1), and islets coincubated with +/+ sera (1.9 +/- 0.4, P < 0.01). We conclude that prolonged exposure of human islets to sera positive for the presence of CD38Abs with [Ca(2+)](i)-mobilizing activity impairs beta-cell function and viability in cultured human pancreatic islets.

ADP-ribosyl Cyclase↗