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Biomedical subjects

A Antonelli

Publications and source records attributed to A Antonelli.

At least 19 recordsLinked to original sources
PubMed2006

Effect of L-thyroxine treatment on left ventricular function in subclinical hypothyroidism.

Aim of this study was to investigate the effects of thyroxine treatment on myocardial regional left ventricular (LV) systolic and diastolic function in patients with subclinical hypothyroidism (SH) by tissue Doppler imaging (TDI). Forty-two patients (29 women and 13 men; mean age 52.2+/-15.1 years) with SH, as judged by elevated serum thyroid-stimulating hormone (TSH) levels (>3.6 mIU/l; range, 3.8-12.0) and free thyroid hormones (FT4 and FT3) within the normal range, and 30 euthyroid volunteers (21 women and nine men; mean age 50.4+/-17.1 years) underwent standard echocardiography and TDI-derived early (Em) and late (Am) diastolic velocities, systolic (Sm) velocity, and isovolumetric relaxation time (IVRTm). Patients were randomly assigned to receive or not L-thyroxine replacement therapy. All patients returned after 6 months to repeat thyroid function tests and the evaluation of all parameters. No significant differences were seen in the Sm peak between SH and control groups. Respect to controls, SH patients exhibited a lower Em, a higher Am, and, subsequently, a reduced Em/Am ratio of both lateral wall (LW) and interventricular septum (IVS) (P<0.001 for both). The IVRTm was distinctly longer in SH patients, as compared to controls (P<0.001). At 6 months, L-thyroxine-treated patients showed a significant increase of Em (P<0.01) and a subsequent increase of the Em/Am ratio (P<0.01), whereas IVRTm significantly reduced (P<0.05). No significant change in any of these parameters was observed in the untreated group. Our data suggest that SH is associated with a subtle, reversible impairment of myocardial function. TDI analysis detects and extends these functional defects by displaying alterations in regional myocardial function. L-T4 replacement therapy should be advised for these patients with the aim to correct preclinical cardiac dysfunction and prevent the development of clinically significant myocardial dysfunction.

Echocardiography, Doppler↗
PubMed2006

Heart rate variability and QT dispersion in patients with subclinical hypothyroidism.

UNLABELLED: The effect of subclinical hypothyroidism (SH) on cardiovascular autonomic function and ventricular repolarization has not been yet elucidated. The aim of the present study was to evaluate the dispersion of QT interval, i.e. an index of inhomogeneity of repolarization, and heart rate variability (HRV), i.e. a measure of cardiac autonomic modulation, in SH patients. METHODS: The study included 42 patients (29 women and 13 men; mean age 53.2+/-14.2 years; body surface area 1.76+/-0.14 m2) with SH, as judged by elevated serum TSH levels (>3.6 mIU/l; range, 3.8-12.0) and normal free thyroid hormones (FT4 and FT3) and 30 euthyroid volunteer. Subjects with cardiac, metabolic, neurological disease or any other systemic disease that could affect autonomic activity were excluded from the study. Patients with SH and control subjects underwent a full history, physical examination, standard 12-lead ECG, and 24-h ambulatory ECG monitoring. To evaluate the effect of treatment with L-thyroxine on QT dispersion and HRV, 15 patients with SH were randomly assigned to receive therapy with L-thyroxine. All the subjects were evaluated at enrolment and after 6 months. RESULTS: Patients with SH showed higher QT dispersion and lower HRV measures than healthy controls (P<0.01 for all). In SH patients, the standard deviation of N-Ns (SDNN) was negatively related to TSH (r=-0.42, P=0.006), while low frequency (LF)/high frequency (HF) ratio was positively related to TSH (r=0.42, P=0.006). Moreover, in SH patients both QT dispersion and QTc dispersion were positively related to TSH (r=0.64 and r=0.63, P<0.001 for both). After 6 months, the patients treated with L-tiroxine exhibited a reduction of QT dispersion and an increase of HRV parameters. CONCLUSION: The results of the present study demonstrated that SH can alter autonomic modulation of heart rate and cause increased inhomogeneity of ventricular recovery times. Accordingly, early L-thyroxine treatment may be advised not only to prevent progression to overt hypothyroidism but also to improve abnormal cardiac autonomic function and ventricular repolarization inhomogeneity.

Electrocardiography↗
PubMed2006

Characterization and biological activity of the main flavonoids from Swiss Chard (Beta vulgaris subspecies cycla).

The molecular components of a phenolic fraction (P2), obtained from liquid chromatography of a Swiss Chard (Beta vulgaris subsp. cycla) extract, were identified using HPLC-ESI-MS/MS. The primary P2 components were: vitexin-2''O-rhamnoside, its demethylated form 2''-xylosylvitexin, isorhamnetin 3-gentiobioside, and rutin. P2 "in toto" and the single components were characterized for antioxidant capacity, antimitotic activity on MCF-7 human breast cancer cells and for toxicity to human lymphocytes and macrophages. P2 inhibited MCF-7 cell proliferation (IC(50) value = 9 microg/ml) without inducing apoptosis, showed no toxicity to human lymphocytes and slight toxicity to macrophages. Vitexin-2''O-rhamnoside strongly inhibited DNA synthesis in MCF-7 cells, whereas 2''-xylosylvitexin and isorhamnetin 3-gentiobioside were activators; combinations of activators and inhibitors maintained the over-all inhibitory effect.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Serum levels of the interferon-gamma-inducible alpha chemokine CXCL10 in patients with active Graves' disease, and modulation by methimazole therapy and thyroidectomy.

BACKGROUND: The interferon-gamma-inducible chemokine CXCL10 is highly expressed in infiltrating inflammatory cells, and in thyrocytes in patients with Graves' disease. The aim of this study was to measure serum levels of CXCL10 in relation to thyroid function and treatment. METHODS: Serum levels of CXCL10 were measured in 22 patients with Graves' disease when hyperthyroid, when euthyroid under methimazole therapy, and 3 days after near-total thyroidectomy. They were compared with levels in three groups of age- and sex-matched controls: 44 subjects with no thyroid disorder, 44 patients with euthyroid autoimmune thyroiditis and 20 with toxic nodular goitre. RESULTS: Basal serum levels of CXCL10 in patients with Graves' disease were higher than levels in patients with toxic nodular goitre or no thyroid disorder, and similar to levels in patients with autoimmune thyroiditis (mean(s.d.) 167(121), 100(24), 78(46) and 142(107) pg/ml respectively; P < 0.010). Among patients with Graves' disease, serum levels of CXCL10 were significantly higher in those aged over 50 years (P = 0.010), with a hypoechoic pattern at thyroid ultrasonography (P < 0.001) or with hypervascularity (P = 0.001). CXCL10 levels in patients with Graves' disease decreased significantly when euthyroidism was achieved by methimazole therapy (P < 0.010), and a further decrease was observed after thyroidectomy (P < 0.010). CONCLUSION: Serum levels of CXCL10 are higher in newly diagnosed hyperthyroid patients with Graves' disease than in those with toxic nodular goitre, and decrease when euthyroidism is achieved with antithyroid therapy. This high level may be related to the active inflammatory phase of Graves' disease. A further reduction of CXCL10 levels after thyroidectomy indicates that it is produced mainly in the thyroid in patients with autoimmune thyroid disease.

Antithyroid Agents↗
PubMed2006

Spatial memory deficits in middle-aged mice correlate with lower exploratory activity and a subordinate status: role of hippocampal neurotrophins.

The aim of the present work was to relate age-related individual differences in cognitive function with behavioural strategies employed in social and non-social challenges. To this purpose, the behaviour of adult (5-month-old) and middle-aged (13-month-old) CD-1 mice was scored in the social interaction, plus-maze, Morris water maze (MWM) and open-field tests. In addition, brain levels of nerve growth factor and brain-derived neurotrophic factor (BDNF) were analysed and correlated with the behaviours scored. Compared to adults, middle-aged mice showed greater anxiety in both non-social and social situations, spending less time in the open arms of the plus-maze and performing more freezing behaviour in response to aggression. Based upon their behaviour in the social interaction test, adult and middle-aged subjects were classified as dominant or subordinate and their behaviour in the open field, plus-maze and MWM tests subjected to factor analysis, taking into account age and social status. Results highlighted meaningful differences in exploratory strategies as a function of social status only in middle-aged subjects. In particular, middle-aged dominants were, overall, more explorative than same-aged subordinates, spending less time in peripheral areas and approaching more readily a novel object. Interestingly, in middle-aged mice, superior performance in the MWM task was associated with exploratory strategies exploited by dominants. At adulthood, BDNF hippocampal levels, but not specific behaviours, were positively correlated with the ability to learn a spatial task. Overall, data indicate that, in middle-aged subjects individual differences in exploratory strategies, rather than neurotrophin levels, are able to predict the degree of impairment in a spatial learning task.

Age Factors↗
PubMed2005

The pro-fibrogenic effect of nerve growth factor on conjunctival fibroblasts is mediated by transforming growth factor-beta.

BACKGROUND: Nerve growth factor (NGF) and nerve growth factor receptor (NGFR) expressions have been found to be increased in sub-conjunctival scarring. OBJECTIVE: The aim of this study was to investigate the in vitro effects of NGF on some pro-fibrogenic properties of human conjunctival fibroblasts. METHODS: Expression of NGF, trkA(NGFR) and p75NTR on human fibroblasts grown from conjunctival biopsies and incubated for 2 or 6 days with NGF were evaluated by immunofluorescence, RT-PCR, flow cytometry and ELISA. The fibrogenic effect of NGF on conjunctival fibroblasts was investigated by evaluating their migration (wound model), proliferation ([3H]-thymidine incorporation), collagen production (3H]-proline incorporation), expression of alpha-smooth muscle actin (alpha-SMA) (cell surface ELISA) and contraction of 3D collagen gels. RESULTS: NGF induced the expression of p75NTR in the fibroblasts that constitutively expressed only trkA(NGF) and increased the migration of wounded fibroblasts, but not their proliferation and collagen production. NGF induced the conversion of fibroblasts into myofibroblasts expressing alpha-SMA, and enhanced their contraction of a collagen matrix. Interestingly, chronic NGF treatment induced transforming growth factor-beta1 (TGF-beta1) production by fibroblasts, and following specific TGF-beta neutralization, all the NGF-induced effects were completely abrogated. CONCLUSION: Our findings indicate that NGF, via TGF-beta induction, is likely to be involved in the healing or fibrotic processes occurring in conjunctiva during some pathological conditions.

Actins↗
PubMed2005

Anti-CD38 autoimmunity in children with newly diagnosed type 1 diabetes mellitus.

AIMS: To test for anti-CD38 autoimmunity in children with newly-diagnosed type 1 diabetes mellitus (DM1). METHODS: Serum anti-CD38 autoantibodies were detected by Western blot in 270 children (130 girls, 140 boys, mean age 8 +/- 4 years) with newly-diagnosed DM1 and 179 gender- and age-matched non-diabetic children. In 126 diabetic children, another blood sample was obtained 15 +/- 4 months after the diagnosis. RESULTS: Anti-CD38 autoantibody titers at least 3 SD above the mean value for the control group were found in 4.4% of children with DM1 vs 0.6% of controls (chi2 = 5.8, p <0.016). No statistical differences were observed between anti-CD38 positive and negative patients in terms of phenotype. At follow-up, of six diabetic children who were positive for anti-CD38 antibodies, two were new cases. A positive correlation was found between the antibody titer of diabetic sera at diagnosis and follow up (r = 0.46, p <0.0001). CONCLUSION: An autoimmune reaction against CD38, a protein expressed in human islets, is associated with newly-diagnosed DM1. In children with DM1, CD38 autoimmunity increases with time and persists.

ADP-ribosyl Cyclase 1↗
PubMed2004

Stacking-fault based microscopic model for platelets in diamond.

We propose a new model for {001} platelets in diamond based on the formation of a metastable stacking-fault. The core of the defect is a double layer of threefold coordinated sp2 carbon atoms embedded in the sp3 diamond matrix. The properties of the model were determined using ab initio calculations. All significant experimental signatures attributed to the platelets are fully accounted for. The model is also very appealing from the point of view of kinetics, since naturally occurring shearing processes will lead to the formation of the metastable fault.

Journal Article↗
PubMed2004

In vitro human ependymoblastoma cells differentiate after exposure to nerve growth factor.

Nerve Growth Factor (NGF) has a prominent action on immature crest-derived nerve cells and on differentiation and survival of neurons in central and peripheral nervous system. NGF is produced by a variety of neuronal and non-neuronal cells, including neoplastic cells. Its role in tumor cells is largely unknown and controversial. The aim of the present study was to investigate the effect of NGF on brain neoplastic cells using primary cultures from ependymoblastoma (EP) tissue. Human EP tissues were cultured to obtain in vitro cells and their structural, biochemical, and molecular responses to NGF were investigated. The results showed that under basal conditions, human EP cells are characterized by low presence of high-affinity NGF-receptors. Time-course and dose-response studies revealed that EP cells undergo differentiation after exposure to NGF. Our findings showed that in human EP cells, NGF exerts a marked action on differentiation rather than proliferation.

Adolescent↗
PubMed2004

Nerve growth factor and brain-derived neurotrophic factor in human paediatric hemimegalencephaly.

Paediatric hemimegalencephaly (HME) is a congenital central nervous system (CNS) disorder, characterized by monolateral cerebral hemisphere enlargement, intractable seizures starting in the post-neonatal period, and mental retardation associated with neuropathological anomalies (mainly cortical thickness and lack of lamination). Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are two neurotrophic factors produced in the mammalian CNS that are involved in the survival, development, and function of a variety of brain cells. In the present study, we found increased cerebral tissue levels of NGF and BDNF in 4 infants with HME; these changes appear to be also associated with abnormal NGF-receptor expression in subcortical blood vessels. Moreover, the marked reduction of cortical choline acetyltransferase immunoreactivity is strongly suggestive of a dysregulation in the NGF differentiative activity in this site that could lead to the pathogenesis of HME.

Antibodies↗
PubMed2004

Expression of neurotrophic factors in cerebrospinal fluid and plasma of children with viral and bacterial meningoencephalitis.

AIM: To evaluate the expression of neurotrophic factors (nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF)) and their association with the clinical-radiological characteristics and outcome of children with viral and bacterial meningoencephalitis (ME). METHODS: Prospective observational clinical study performed on 13 children with ME and 12 controls with non-inflammatory obstructive hydrocephalus. Neurotrophic factor levels in the cerebro-spinal fluid (CSF) and plasma were measured using an immunoenzymatic assay. RESULTS: High levels of NGF and BDNF were demonstrated in all patients, while GDNF levels did not undergo significant variations. NGF expression in the CSF was higher in viral ME than in bacterial ME and was correlated with CSF cellularity (particularly mononuclear cells). BDNF expression in the CSF was higher in bacterial ME than in viral ME and was correlated with CSF cellularity and blood platelet count. No relationships were noted between CSF protein or serum C-reactive protein levels and the expression of neurotrophic factors. Regarding clinical and radiological features, elevated NGF/BDNF levels in the CSF correlated with higher incidence of seizures and prolonged comatose state and with specific radiological lesions. No correlation was found between NGF/BDNF levels and final outcome. CONCLUSIONS: The variations in neurotrophic factor levels may reflect an endogenous attempt at neuroprotection against biochemical and molecular changes during both viral and bacterial ME. The expression of these factors is likely to play a neuro-immunomodulatory or neurosurvival role in ME infections.

Case-Control Studies↗
PubMed2004

Thyroid involvement in patients with overt HCV-related mixed cryoglobulinaemia.

BACKGROUND: Mixed cryoglobulinaemia (MC), a systemic vasculitis associated with hepatitis C virus (HCV) infection in >90% of cases, is frequently complicated by multiple organ involvement. The prevalence of thyroid disorders in MC has not yet been studied. AIM: To investigate the prevalence and clinical features of thyroid involvement in patients with HCV-associated MC (HCV + MC). DESIGN: Case-control study. METHODS: HCV + MC patients (n = 93, 17 men and 76 women, mean +/- SD age 63 +/- 10 years, mean disease duration 14 +/- 7 years) consecutively referred to the Rheumatology Unit were matched by sex and age (+/- 2 years) to (i) 93 patients with chronic C hepatitis (CH) without MC and (ii) 93 healthy (HCV-negative) controls from the local population. Measurements included prevalence of hypo- or hyperthyroidism, thyroid autoantibodies, thyroid nodules and thyroid cancer. RESULTS: By McNemar's chi(2) test, the following thyroid abnormalities were significantly more frequent in HCV + MC patients than in HCV-negative controls: serum anti-thyroperoxidase autoantibody (AbTPO) (28% vs. 9%, p = 0.001); serum AbTPO and/or anti-thyroglobulin autoantibody (31% vs. 12%, p = 0.004); subclinical hypothyroidism (11% vs. 2%, p = 0.038); thyroid autoimmunity (35% vs. 16%, p = 0.006). Serum AbTPO were also significantly more frequent in HCV + MC patients than in CH controls (28% vs. 14%, p = 0.035). DISCUSSION: The prevalence of thyroid disorders is increased in patients with HCV-related mixed cryoglobulinaemia. We suggest careful monitoring of thyroid function in these patients.

Aged↗
PubMed2004

Chromosome instability in T-cells cultured in the presence of pancuronium or fentanyl.

BACKGROUND: Genomic instability is recognized as a cause of cellular apoptosis and certain drugs that exhibit a proapoptotic effect are also able to induce chromosome damage. Since we found in recent experiments that drugs such as pancuronium and fentanyl exerted an apoptogenic effect on T cells, we studied the capacity of those agents to promote chromosome instability, i.e. chromosome aberrations (CA) and telomeric associations (tas) in peripheral blood lymphocytes. METHODS: Lymphocytes from healthy donors were cultured with pancuronium or fentanyl, using two different concentrations for each drug: 20 and 200 ng/ml for pancuronium and 10 and 30 ng/ml for fentanyl, respectively. Cells were exposed to each concentration of these drugs either for 24 or 48 h. The higher concentration chosen was the same at which we detected the proapoptotic effect in our previous works. Cytogenetic analysis was performed by means of a standard technique and chromosome aberrations or telomeric associations were blindly evaluated by two independent observers. RESULTS: The chromosome aberrations we observed in treated cells were not significantly different from control lymphocytes. However, an unusual rate of telomeric associations (P < 0.001) was detected in cells exposed to both pancuronium and fentanyl, at each concentration tested and at each exposure time of the study. CONCLUSIONS: Fentanyl and pancuronium do not have a direct clastogenic effect on T cultures, but at the same concentrations at which we demonstrated their apoptogenic power, these drugs are able to increase genomic instability through inducing an elevated rate of telomeric associations. Such a capacity could exploit in peripheral T cells the same mitochondrion-mediated signal pathway of apoptosis death.

Adult↗
PubMed2003

Type 2 diabetes in hepatitis C-related mixed cryoglobulinaemia patients.

OBJECTIVES: Mixed cryoglobulinaemia (MC) is a systemic vasculitis frequently associated with hepatitis C virus (HCV) infection. A possible link between HCV infection and type 2 diabetes has been suggested. This study evaluated the prevalence and clinical phenotype of diabetes in MC-HCV+ patients. METHODS: Two hundred and twenty-nine consecutively recruited MC-HCV+ patients were compared with 217 sex- and age-matched controls without HCV infection. RESULTS: The prevalence of type 2 diabetes was significantly higher in MC-HCV+ patients than in controls (14.4 vs 6.9%, P < 0.01). Diabetic MC-HCV+ patients were leaner than diabetic patients without MC-HCV (P < 0.0001), and showed significantly lower total and low-density lipoprotein cholesterol levels (P < 0.001) and lower systolic (P = 0.01) and diastolic blood pressure (P = 0.005). MC-HCV+ diabetic patients had non-organ-specific autoantibodies more frequently (34 vs 18%, P = 0.032) than non-diabetic MC-HCV+ patients. CONCLUSIONS: The prevalence of type 2 diabetes is higher in patients with MC-HCV than in controls. Diabetic MC-HCV+ patients show an attenuated diabetic phenotype and are more likely to carry non-organ-specific autoantibodies.

Aged↗
PubMed2003

Telomerase activity, apoptosis and cell cycle progression in ataxia telangiectasia lymphocytes expressing TCL1.

Individuals affected by ataxia telangiectasia (AT) have a marked susceptibility to cancer. Ataxia telangiectasia cells, in addition to defects in cell cycle checkpoints, show dysfunction of apoptosis and of telomeres, which are both thought to have a role in the progression of malignancy. In 1-5% of patients with AT, clonal expansion of T lymphocytes carrying t(14;14) chromosomal translocation, deregulating TCL1 gene(s), has been described. While it is known that these cells can progress with time to a frank leukaemia, the molecular pathway leading to tumorigenesis has not yet been fully investigated. In this study, we compared AT clonal cells, representing 88% of the entire T lymphocytes (AT94-1) and expressing TCL1 oncogene (ATM(-) TCL1(+)), cell cycle progression to T lymphocytes of AT patients without TCL1 expression (ATM(-) TCL1(-)) by analysing their spontaneous apoptosis rate, spontaneous telomerase activity and telomere instability. We show that in ATM(-) TCL1(+) lymphocytes, apoptosis rate and cell cycle progression are restored back to a rate comparable with that observed in normal lymphocytes while telomere dysfunction is maintained.

Antineoplastic Agents, Phytogenic↗
PubMed2003

The collecting duct carcinoma of the kidney: a cytogenetical study.

OBJECTIVES: The Heidelberg classification of renal tumours identifies five histotypes of renal cancer, underlining for two of them (conventional and papillary renal cancers) a strict relation between the morphological aspect and the complement of alterations evidenced by the cytogenetic analysis of the neoplastic karyotype. Due to its low incidence, the collecting duct carcinoma (CDC) has not yet been characterized from a cytogenetic point of view. This study analyses the clinical, morphologic and cytogenetic features of the CDC observed and treated in our department. METHODS: From January 1995 to December 2002, among the 591 patients who underwent surgery for renal cancer, we observed 11 cases of CDC (prevalence 1.9%) treated either by radical (9 cases) or partial nephrectomy (2 cases). During radical nephrectomy a loco-regional lymphadenectomy was always performed. In the 9 cases observed after 1997, a complete cytogenetic analysis of the neoplastic karyotype was carried out. RESULTS: At pathological examination the disease was found to be confined to the renal capsule (TNM 1997 stage 1) in only 3 patients; venous neoplastic trombosis and nodal metastasis were present in 3 and 6 cases respectively; 2 patients showed distant metastases (lung, bone). Two of the patients affected with stage 1 tumours are still alive with no evidence of the disease at 48 and 88 months after surgery, while the third died following the systemic progression of a concomitant bladder carcinoma. One patient with stage 4 tumour (no. 11) is alive, but the follow up time is still limited (2 months). All the other 7 patients are dead after a mean survival time of 16.3 months (range 0-45). As for cytogenetic analysis, 2 CDCs didn't grow in culture and in one case no karyotype alterations were reported. In the remaining 6 cases hypodiploid stemlines and a homogeneous chromosome alteration pattern were observed, with multiple numerical and structural aberrations (mean 11.1, range 7-15) and the continuous involvement of chromosomes 1 and X or Y, both as traslocation and deletion/monosomy. Additional abnormalities of chromosomes 22 and 13 were found to be common but less frequent. CONCLUSIONS: The clinical behaviour of the CDC is aggressive and its prognosis is surely poor; surgical treatment seems to be curative only for organ-confined cancer, accounting for the minority of cases. This neoplasm is cytogenetically characterized by hypodiploid stemlines with common involvement of chromosome 1 and the autosomes.

Aged↗
PubMed2002

Autoimmunity to CD38 and GAD in Type I and Type II diabetes: CD38 and HLA genotypes and clinical phenotypes.

AIMS/HYPOTHESIS: Autoantibodies against CD 38 have been found in some patients with Type II (non-insulin-dependent) diabetes mellitus and have been shown to stimulate insulin secretion by cultured human islets. We tested whether this new form of autoimmunity, (i). overlaps with anti-GAD autoimmunity, (ii). identifies an insulin-deficient phenotype, (iii). is under the influence of genetic factors. METHODS: We screened 496 adults by immuno-blot analysis in the Botnia Study (298 with Type II and 98 with Type I (insulin-dependent) diabetes mellitus, 100 non-diabetic control subjects). RESULTS: CD 38-autoantibodies were found in 8.4% of Type II diabetic patients ( p<0.003 vs 0% of control subjects), particularly in anti-GAD positive (14% vs 6% of anti-GAD negative, p=0.0004). CD 38 ab were also found in 4% of Type I diabetic patients; in the whole study group, 59% of anti- CD 38 positive had DQB1*02 compared with 38% of anti-CD 38 negative ( p=0.04). On the OGTT, beta-cell function (as the ratio of insulin-to-glucose areas) was impaired ( p=0.02) only in association with anti-GAD positivity (3.2+/-3.1 U/mol, mean +/- SD) but not in anti- CD 38 positive patients (5.6+/-2.9) as compared with patients free of autoimmunity (4.5+/-4.6, p=NS). In 44 Type II diabetic patients (22 negative and 22 positive for anti- CD 38), no mutations were detected in any of the 8 exons, 5' end of intron 1 or the 5' and 3' untranslated regions of the CD 38 gene. The previously described missense mutation (Arg140Trp) in exon 3 was not found in this cohort. There was no association between the PvUII polymorphism and clinical phenotype. CONCLUSION: Anti-CD 38 autoimmunity identifies a clinical phenotype similar to non-autoimmune Type II diabetes, with relative preserved beta-cell function and weak genetic influence.

ADP-ribosyl Cyclase↗