Biomedical subjects

D Maugendre

Publications and source records attributed to D Maugendre.

At least 37 records · Page 2Linked to original sources

PubMed1997

Clinical validity of intercellular adhesion molecule-1 (ICAM-1) and TSH receptor antibodies in sera from patients with Graves' disease.

We compared the concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and the activities of thyroid-stimulating antibodies (TSAb) and thyrotropin-receptor antibodies (TBIAb) as measured with a commercial kit (TRAK). Sera were obtained from patients with Graves' disease (GD) before, during and after therapy with carbimazole (1-methyl-2-thio-3-carbethoxyimidazole). In all the situations, TSAb method was more sensitive than TBIAb. These two parameters dropped during therapy and were not correlated at any stage of measurement. sICAM-1 levels increased in 56.4% of patients before treatment, remained elevated at the beginning of treatment and decreased after twelve months of therapy. TSAb levels were significantly different between patients in relapse (78%) and those in remission (18%) (Z = -2.250, P = 0.025), with a relapse rate depending on the TSAb positivity (chi 2 = 7.103, P = 0.0077). Positive sICAM-1 values were found in 3 of the 9 (33.3%) patients who relapsed after discontinuing the drug but were negative in all the patients remaining in remission with a significant difference (Z = -1.982, P = 0.0475). The relapse rate was also dependent on positive sICAM-1 values (chi 2 = 3.958, P = 0.0466). No correlation was found between sICAM-1 levels and anti-TSH receptor antibodies TSAb or TBIAb. We conclude that the TBIAb technique is too insensitive to explore GD. TSAb and sICAM-1 assays in patients with GD are good markers of immune process after treatment withdrawal. Because of its rapid implementation, the sICAM-1 assay may advantageously replace TSAb measurement for forming a prognosis of GD.

Antibodies↗

PubMed1997

Impaired leucocyte functions in diabetic patients.

This study evaluates polymorphonuclear neutrophil (PMN) cell performance in 61 diabetic patients free of infection (40 Type 1, 21 Type 2), using tests that explore all the functional steps of PMN: (1) adherence: expression of adhesion molecules, CD 11a, CD 11b, CD 11c; nylon fiber adherence test; (2) chemotaxis under agarose towards the bacterial oligopeptide FMLP and complement fractions, used as attracting agents; (3) phagocytosis of opsonized latex microbeads; (4) bactericidal activity: chemiluminescence assessment of the oxidative killing potential before and after stimulation by opsonized zymosan and PMA; nitroblue tetrazolium reduction test. Results were analysed according to potentially influential factors: metabolic control (HbA1C, glycaemia), age of patient, type of diabetes, disease duration, and existence of vascular complications. PMN chemotaxis was significantly lower in patients than in healthy controls (p < 0.001) and associated with spontaneous adherence and increased expression of adhesion molecules (CD 11b, CD 11c). The increased response to chemiluminescence reflects spontaneous activation of PMN cells and increased free radical production; after stimulation, response was lower than in controls. The type of diabetes, the age of patients, HbA1C level and disease duration did not affect the responses. Chemotaxis and chemiluminescence were further reduced in patients with vascular complications and hyperglycaemia. We conclude that all steps of PMN functioning are altered in diabetic patients, which may increase the risk of vascular complications and infectious episodes.

Adult↗

PubMed1997

Anti-pancreatic autoimmunity and Graves' disease: study of a cohort of 600 Caucasian patients.

The aim of this study was to investigate the frequencies of clinical diabetes and humoral markers of anti-pancreatic autoimmunity in a homogeneous population of 600 Caucasian patients with recently diagnosed Graves' disease (GD), in order to characterize the specific features of this group of endocrine patients among subjects at risk of diabetes. Ten were already diabetic at GD diagnosis. Among the 590 non-diabetic patients, 29 had islet cell antibodies (ICA), including 15 with low titre ICA and only 1 ICA-positive subject with a familial history of diabetes. Twenty-four patients had insulin autoantibodies, including three in association with ICA. Glutamic acid decarboxylase (GAD)/64 kDa antibodies were found in 16 of the 150 tested sera, including 13 of the 29 ICA-positive sera. Four ICA-positive patients displayed 37/40 kDa antibodies, including three in association with GAD/64 kDa antibodies. During follow-up, one of the ICA-positive patients developed insulin-dependent diabetes, 14 years after the GD diagnosis. To summarize, this anti-pancreatic autoimmunity study was focused on a large but specific and homogeneous group of subjects at risk for diabetes: recently diagnosed GD patients. This population was characterized by a high prevalence of GAD/64 kDa antibodies but also by a low frequency of evolution towards diabetes and the slowness of the process which could be due to the fact that only a minority of subjects possessed a sufficient combination of anti-pancreatic markers at the same time.

Adult↗

PubMed1997

Expression of membrane and soluble intercellular adhesion molecule-1 in Graves' disease.

We have investigated the in vitro expression of membrane and soluble intercellular adhesion molecule-1 (ICAM-1) by human thyroid cells from 20 patients with Graves' disease and 5 normal subjects. Membrane ICAM-1 was not detected by flow cytometry analysis in non-cultured thyrocytes from either normal or Graves' disease tissues. It appeared on thyroid cells after a 24-h culture in monolayers and showed a regular dose-dependent increase. The same results were obtained with soluble ICAM-1 (sICAM-1) in culture media from cells cultured in monolayers, vesicles or follicles. No change was obtained with different concentrations of fetal calf serum added to the media. Coculture of Graves' disease thyrocytes with autologous peripheral blood lymphocytes (PBL) or intrathyroidal lymphocytes (ITL) enhanced the expression of both membrane and sICAM-1 whatever the culture model. When normal thyrocytes were cocultured with PBL, sICAM-1 increased but with ITL sICAM-1 remained unchanged. High concentrations of gamma interferon induced an increase of both membrane and sICAM-1 in the three culture models. However the increases were greater with vesicles and follicles. Only sICAM-1 levels were raised with 0.1, 1 and 10 microM retinoic acid. These results suggest that ICAM-1 appears in culture, possibly due to mechanical effects such as adherence to plates and cell-to-cell contacts. Moreover, its expression is modulated by several factors such as cytokines or retinoic acid. Further investigations are needed to establish whether ICAM-1 is really involved in the pathogenesis of Graves' disease.

Adult↗

PubMed1997

Increased prevalence of thyroid autoantibodies and subclinical thyroid failure in relatives of patients with overt endocrine disease-associated diabetes but not type 1 diabetes alone.

The purpose of this study was to determine the prevalence of thyroperoxidase (TPO) and thyroglobulin (Tg) antibodies, using a sensitive and specific radioimmunoassay method in a large cohort of 254 first-degree relatives of Type 1 diabetic patients with or without other autoimmune endocrinopathy, and to evaluate the predictive value of thyroid antibodies for impaired thyroid function in these groups. TPO and Tg antibodies were found at similar frequencies (12%) in the 254 relatives, and both antibodies were present in 23 cases (9%). Seven subjects displayed subclinical thyroid dysfunction without an abnormal free T4 level. Among first-degree relatives of probands with Type 1 diabetes alone, TPO or Tg antibodies were found in 8 subjects (6%), including 6 with both antibodies. The prevalence of TPO antibodies was significantly greater among relatives of TPO-positive than TPO-negative probands (p < 0.01). In relatives of diabetic patients with other endocrinopathy, frequencies of TPO (20%), Tg (19%) and a combination of both antibodies (15%) were significantly higher than in relatives of Type 1 diabetic patients without endocrinopathy (p < 0.001). TSH levels were abnormal in only one relative of the group without endocrinopathy but occurred in 6 relatives of the proband with overt endocrinopathy-associated diabetes (p < 0.02) in marked association with TPO antibodies (p < 10(-4). It is concluded that relatives of probands with overt endocrine autoimmune disease-associated diabetes, unlike those of probands with diabetes alone, showed increased prevalence of thyroid antibodies and thyroid dysfunction. These results argue for a different risk of thyroid autoimmunity and clinical disease in families of diabetic patients without or with overt endocrine disease. A screening of thyroid autoimmunity is highly recommended for the latter group.

Adolescent↗

PubMed1997

Multiple antibody status in type 1 diabetic patients and subjects at various risk with islet-cell antibodies.

The frequency of 37/40 kD antibodies and their association with other pancreatic humoral markers were studied in 109 recently diagnosed Type 1 diabetic patients and 116 subjects with islet-cell antibodies (ICA) at various risk for this disease (64 relatives of Type 1 diabetic patients, 23 schoolchildren with no family history of diabetes, and 29 patients with Graves' disease). At the time of diagnosis, 37/40 kD antibodies were detected in 45% of Type 1a and 77% of Type 1b diabetic patients (p = 0.03). Antibodies to glutamic acid decarboxylase (GAD) and/or 37/40 kD were present with the same frequency as ICA (86%). The frequency of 37/40 kD antibodies was not significantly different between the 3 groups at risk, in contrast with GAD antibodies which were found at a lower frequency in schoolchildren (p < 0.02). Frequencies of other pancreatic markers (ICA cross-reactive with mouse pancreas and insulin autoantibodies) and the combination of ICA with at least two other markers were significantly higher in relatives than in the other groups at risk (p < 0.02). Out of 116 ICA-positive non-diabetic subjects, 10 developed diabetes. All 10 displayed 37/40kD and/or GAD antibodies during the prediabetic phase. In 8 of these 10 patients, ICA was combined with at least two other markers, whereas this association was detected in only 17 of the remaining 106 subjects who did not progress to diabetes (p < 10(-4). Thus, 37/40 kD antibodies were found in about half of Type 1 diabetic patients, and with a higher-frequency in Type 1b than 1a. In ICA-positive non-diabetic subjects, our date confirm that a combination of multiple antibodies, including GAD antibodies and 37/40 kD antibodies, can enhance the predictive value for diabetes. Comparison of ICA-positive relatives of diabetic patients, schoolchildren and patients with Graves' disease revealed distinct frequencies and combinations of markers of diabetes. This might reflect different patterns of progression among these 3 groups.

Animals↗

PubMed1996

Differential beta-cell response to glucose, glucagon, and arginine during progression to type I (insulin-dependent) diabetes mellitus.

Acute insulin responses to glucose (AIRG), glucagon (AIRGln), and arginine (AIRArg) were evaluated prospectively in nine subjects positive for islet-cell antibodies (ICAs) who later progressed to type I diabetes or impaired glucose tolerance (IGT) (progressors), 64 ICA-positive subjects at risk who did not develop type I diabetes, 365 ICA-negative relatives of diabetic patients who also remained free of the disease, and 89 control subjects. Seven progressors already had a low AIRG at entry into the study, and the other two became low responders 3 to 9 months before diabetes or IGT, with a progressive decline of AIRG over serial intravenous (IV) glucose tolerance tests. At entry into the study, the group of progressors displayed lower AIRG, AIRGln, and AIRArg than the other three groups (P<.001). However, AIRArg was less altered than AIRG. During the course of the prediabetic phase, there was a progressive decline in AIRG and AIRGln analyzed as a function either of time (P<.006) or of basal glycemia (P<.05), ie, two different ways of estimating worsening of the disease process. Conversely, there was no significant decrease in AIRArg with time or with increasing basal glycemia, so that AIRArg was not totally blunted in these prediabetic subjects even a few months before the onset of diabetes. The persistence of a substantial response to arginine, ie, higher than the fifth control percentile, even at a late stage, was confirmed in five of nine diabetic patients tested either at onset of the disease or during non-insulin-receiving remission. Whereas AIRG deteriorates during prediabetes, AIRArg appears to be less altered with time and increased basal glycemia, remaining substantial even at the onset of the disease. This reinforces the supposition that the prediabetic state may be associated with a glucose-specific beta-cell functional abnormality in addition to a decreasing beta-cell mass.

Adolescent↗

PubMed1996

Genetic heterogeneity between type 1a and type 1b insulin-dependent diabetes mellitus: HLA class II and TAP gene analysis.

The aim of this study was to compare the genetic susceptibility linked to the HLA Class II region genes of the Major Histocompatibility Complex in isolated insulin-dependent diabetes mellitus (1a-IDDM) and insulin-dependent diabetes mellitus associated with another autoimmune endocrinopathy (1b-IDDM). HLA genes DRB1, DQA1 and DQB1 were studied at the genomic level, as well as genes TAP1 and TAP2. One hundred and seventy-nine 1a-IDDM diabetic patients were compared with 83 1b-IDDM patients. While it appeared that common genetic traits characterize diabetes regardless of the subtype (1a or 1b), certain features differentiate the two forms of IDDM. Extending the analysis of risk haplotypes DRB1*03 and DRB1*04 to TAP genes elicited a difference between 1a-IDDM and 1b-IDDM patients. Haplo-type DRB1*03 was thus characterized in 1a-IDDM patients by a lower frequency of alleles TAP1-B (13.5%) and TAP2-B (16.2%), not found in 1b-IDDM patients (33.3% for each allele). Likewise, haplotype DRB1*04 is characterized in 1b-IDDM patients by a lower frequency of alleles TAP1-C (4.0%) and TAP2-B (8.0%) than in 1a-IDDM patients (22.2% and 25.9%, respectively). In total, this study showed that extending the characterization of HLA Class II haplotypes to TAP genes discriminates between the forms of diabetes restricted to a specific pancreatic affection and those reflecting a wider autoimmune disorder affecting several organs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

[Mass screening of gestational diabetes using O'Sullivan's test in a hospital consultation. Experience in Rennes].

The aim of this work was to study the predictive value of 50 gram glucose O'Sullivan test for systematic screening of gestational diabetes. To confirm the diagnostic the test positivity was controlled by a 100 g, 3 hours oral glucose tolerance test. During a 12-month period, 751 women were included in the 7th month pregnancy consultation. The O'Sullivan test was positive in 18% of cases. The oral glucose tolerance test confirmed the diagnostic in 14% of these positive tests. The frequency of gestational diabetes was about 2.5% in this population. We compared then the results of the test with the other available screening modes. For this purpose, we analysed retrospectively 50 gestational diabetes diagnosed during the same time in the entire pregnant population of the clinic. In our experience, the O'Sullivan's test is a reliable and useful test. It is easy to perform. Less women are selected than in analysis of risk factors (18% versus > 30%), and with better sensitivity.

Adult↗

PubMed1995

HLA-associated heterogeneity of the humoral response to islet antigens in insulin-dependent diabetes.

Insulin-dependent diabetes mellitus (IDDM) is associated with susceptibility HLA class II alleles. Islet cell antibodies (ICA), detected by indirect immunofluorescence on pancreas sections, represent the best marker of the disease. Autoantibodies to glutamic acid decarboxylase (GADA), one major islet antigen, do not totally account for ICA reactivity, suggesting heterogeneity of the anti-islet humoral response. In 97 patients with IDDM we have correlated ICA heterogeneity with clinical markers and DR and DQ alleles. ICA were found in 81% of the patients, and in 33% the serum blocked the binding to islet cells of reference sera with a granular fluorescence pattern. GADA were found in 62% of cases. Patients with high GADA titers and blocking sera were older at onset and less often had a family history of IDDM, suggesting that these antibodies might be a marker of slow progression to IDDM. ICAs were not associated with particular HLA DR or DQ alleles. Conversely, GADA were less frequent than ICA in DR4 subjects but not in the other groups. Moreover, among DR4 non-DR3 patients, GADA were found almost exclusively in DRB1*0401 patients but not in other DR4 subtypes. There was an association of GADA with DQ alleles but it was secondary to linkage disequilibrium between DR and DQ loci. In conclusion, the heterogeneity of the humoral response in IDDM is controlled by HLA class II genes and correlates with clinical heterogeneity.

Adolescent↗

PubMed1995

[Exploration of the various steps of polymorphonuclear neutrophil function in diabetic patients].

UNLABELLED: Vascular complications in diabetic patients is a complex, probably multifactorial phenomena involving cellular phagocytosis. The aim of this study was to evaluate polymorphonuclear performance in 61 infection free diabetic patients based on tests of the different cell functions: 1) adhesion:adhesion molecule expression CD11a, CD11b, CD11c; adhesion test on nylon fibers. 2) chemotaxis:chemotaxis under aragose to FMLP (bacteria oligopeptide) and complement fractions. 3) Phagocytosis:latex beads. 4) Bacteriocidal power:chemoluminescence photometric oxidative potential before and after stimulation with opsonized zymosan and PMA; reduction of tetrazolium nitroblue. RESULTS were analyzed according to type of diabetes, glucose control, duration of the disease, history of infection and presence of vascular complications. RESULTS: compared with a group of 30 controls, the diabetic patients had a significant impaired polynuclear chemotaxis function (p < 0.001) with both spontaneous adhesion and increased expression of adhesion molecules (CD 11b, CD 11c). The chemoluminescence test was increased at the baseline level due to spontaneous polynuclear adhesion and increased production of free radicals. This response decreased after stimulation compared with controls. The type of diabetes, Hb A1c level and history of infection did not appear to have an effect. Inversely, changes in chemotaxis and chemoluminescence were greater in patients with vascular complications. In summary, all the functions of polynuclear neutrophils tested were altered in diabetic patients and could favor vascular complications and infections episodes.

Adult↗

PubMed1994

Combined analysis of islet cell antibodies which cross-react with mouse pancreas, antibodies to the M(r) 64,000 islet protein, and antibodies to glutamate decarboxylase in subjects at risk for IDDM.

With regard to progression to diabetes, ICA cross-reactive with mouse pancreas, antibodies to the M(r) 64,000 islet antigen (64K), antibodies immunotrapping brain GAD activity, and IAA were analysed in 53 ICA-positive first-degree relatives of IDDM patients and 18 ICA-positive schoolchildren without a family history of diabetes. Sera from 29 (55%) relatives did not bind to mouse pancreas, whereas 24 (45%) displayed cross-species reaction. ICA titres on human and mouse pancreas were weakly correlated in the overall population (p < 0.05) but more strongly (p < 0.01) in only those subjects who displayed antibodies on tissues from both species. GAD and 64K antibodies were detected in 31% and 35% of relatives. In schoolchildren, the frequencies of cross-species reactive ICA (22%), GAD antibodies (6%), 64K antibodies (22%), and IAA (6%), were lower (p < 0.05) than in relatives. A strong correlation (p < 0.0001) was observed between GAD and 64K antibodies. GAD or 64K antibodies were strongly correlated with ICA on human pancreas (p < 0.0001) but poorly with ICA on mouse pancreas (p = 0.05). After pre-incubation of sera with brain homogenate, ICA titres were unaffected on mouse pancreas but reduced on human pancreas. ICA-positive subjects who displayed neither cross-species reactive ICA nor GAD or 64K antibodies were more frequent (p < 0.05) among schoolchildren than relatives, whereas subjects who displayed all antibody specificities were more numerous (p < 0.04) in relatives. All relatives with ICA binding only to human pancreas, as well as all schoolchildren, permanently displayed an AIRG higher than the first control percentile and remained non-diabetic.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Combined analysis of islet cell antibodies that cross-react with mouse pancreas, antibodies to the M(r) 64,000 islet protein, and antibodies to glutamate decarboxylase in type I diabetic patients.

OBJECTIVE: A combined analysis of whether islet cell autoantibodies (ICAs) are cross-reactive with mouse pancreas, with glutamate decarboxylase (GAD) antibodies, and with 64K antibodies was performed in a large sample of recently diagnosed type I diabetic patients. The disappearance rates of these different autoantibodies were compared in some patients after onset of the disease. The aims were to determine patterns in GAD/64K antibodies with regard to cross-species reaction of ICA and to assess whether GAD could contribute to ICA positivity in mouse and human pancreases and whether the simultaneous search for all the antibody specificities enhances the detection of autoimmune stigma. RESEARCH DESIGN AND METHODS: ICA detected by immunofluorescence in human and mouse pancreases, antibodies immunoprecipitating the 64K rat islet antigen, and antibodies immunotrapping brain GAD activity were quantified at diagnosis of diabetes in 95 patients and in sequential samples during 1 year after diagnosis in 13 patients. The contribution of GAD to ICA positivity in mouse and human pancreases was evaluated by the analysis of correlations between tests and by the ability of brain homogenate to block ICA reactivity in pancreases from both species. RESULTS: ICAs were detected in human pancreases in sera from 63 (66%) patients, among which 61% bound also to a mouse pancreas. GAD and 64K antibodies were strongly correlated (P < 0.0001) and were detected in 69 and 73% of the patients, respectively. All but two patients with ICA in human pancreas also displayed either ICA in mouse pancreas or GAD/64K antibodies. Among 32 patients without ICA in human pancreas, 54% displayed either GAD/64K antibodies or ICA in mouse pancreas. Only 16% of the patients displayed neither ICA nor GAD/64K antibodies. A correlation (P < 0.005) was found between ICA in human and mouse pancreases. GAD or 64K antibodies were strongly correlated with ICA in human pancreas (P < 0.0001), but not with ICA in mouse pancreas. After preincubation of six sera with GAD-containing brain homogenate, ICA titers were unaffected in mouse pancreas but reduced in human pancreas. ICA titers in mouse pancreas were decreased after 3 months (P < 0.01) in diabetic patients, contrasting with the stability of ICA in human pancreas and GAD antibodies by 1 year after diagnosis. CONCLUSIONS: According to cross-species reaction, we confirm the heterogeneity of ICA in a large series of type I diabetic patients, ICAs that cross-reacted with mouse pancreas being more frequent than ICAs without cross-species reactivity. GAD and 64K antibodies were also present in a majority of patients. The simultaneous search for all the antibody specificities enhances the detection of autoimmune stigma so that only a few patients did not display any autoantibody at diagnosis. GAD is not the target of ICAs in mouse pancreas, whereas GAD accounts for ICA positivity in human pancreas. The conclusion that ICAs in mouse pancreas are not GAD-reactive is reinforced by the fact that they are more transient after onset of diabetes than are GAD antibodies or the complex mixture of ICAs in human pancreas.

Adolescent↗

PubMed1993

Plasma malondialdehyde in type 1 and type 2 diabetic patients.

Malondialdehyde, a marker of lipid peroxidation, was measured as thiobarbituric acid reactive substances (TBARS) in 117 diabetic patients and 53 controls. Patients were divided into groups and subgroups according to the type of diabetes (type 1 and type 2) and the existence or not of vascular complication (macro- or micro-angiopathy). Results showed that TBARS concentrations were significantly higher in type 1 (P < 0.0001) and type 2 (P < 0.001) diabetic patients than in the control group. The plasma TBARS concentrations in type 1 and type 2 diabetic patients did not differ significantly. Among the patients with vascular disease, type 2 diabetic patients with macroangiopathy had significantly higher TBARS concentrations than patients with no vascular complication (P < 0.05). Whichever the type of diabetes, there was no correlation between TBARS concentrations and glycaemic control: glycosylated haemoglobin, fasting blood glucose. This study confirmed the existence of lipid peroxidation disorders in diabetic patients.

Adult↗

PubMed1993

Establishment of T-cell lines from infiltrated NOD islets by stimulation of specific T-cell receptor V beta segments.

The aims of this study were firstly to establish permanent T-cell lines from infiltrated NOD islets, by repeated stimulation of the antigen T-cell receptor with anti-V beta monoclonal antibodies (mAb) and, secondly, to characterize some of their cytotoxic and pathogenic properties. The use of anti-V beta antibodies was aimed at driving the expansion of the T cells in the absence of pancreatic antigen and, at the same time, at selecting lymphocytes expressing a given V beta gene product as an element of their TCR. Twelve lines were established as long-term cultures by regular stimulation with plastic-bound anti-V beta 6 or anti-V beta 8 mAb. The eight lines cultured with anti-V beta 6 mAb were phenotyped as early as one month after initiation and were all V beta 6+/V beta 8-. Three were CD8+ and five CD4+. Of the four lines established with anti-V beta 8 mAb, three were V beta 8+/V beta 6- and one (FD) was unexpectedly phenotyped as V beta 6+/V beta 8-. Clones derived from the FD line confirmed the expression of V beta 6. The cell-mediated cytolytic properties of the 12 lines were evaluated in two independent assays: an antibody-redirected assay to measure the lytic potential irrespective of antigen specificity and a direct cytolytic assay on YAC cells for assessing NK-like activity. The results indicate that practically all the lines (11 out of 12), irrespective of their CD4/CD8 phenotype or V beta expression, can exert cell-mediated cytotoxicity when their TCR/CD3 complex is linked to a target cell. On the other hand, anti-YAC activity is almost exclusively confined to CD8+ cell lines. Pathogenicity was evaluated in two CD4+ T cell lines, one which showed cytolytic activity in the redirected assay but not in the YAC assay (FD) and one which was totally devoid of cytotoxic activity (AH). The two lines were injected into newborn NOD mice with or without CD8+ polyclonal T cells. The results indicate that FD, the cytotoxic line, can induce severe lesions of insulitis when coinjected with polyclonal CD8+ T cells. In contrast, AH, the non-cytotoxic line, injected under the same conditions, induces no lesions. Altogether, the present data demonstrate the feasibility of establishing permanent T-cell lines on the basis of V beta expression.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

[Detection of subjects at risk of type 1 diabetes. GOFEDI. Groupe Ouest-France pour l'Etude du Diabète Insulino-dépendant].

The so-called type 1 (insulin-dependent) diabetes is an autoimmune disease occurring in genetically predisposed subjects. The clinical onset of the disease is preceded by a subclinical period during which insulin-producing cells are progressively destroyed by immunological effectors. This prediabetic phase can be detected by the presence of autoantibodies directed against islet cells and sometimes associated with anti-insulin antibodies in children, and later on by the disappearance of the early insulin secretion peak in response to intravenous glucose. It is at this prediabetic phase that immunomodulators specific to the antipancreas process and devoid of side-effects will be used, when available, and that an early insulin therapy will be instituted.

Biomarkers↗

PubMed1993

[Is thyroid hormone useful in the prevention of nodular recurrence after hemithyroidectomy?].

The frequency of recurrence of thyroid nodule following hemithyroidectomy is variably assessed according to the individual authors. Few studies put a figure to ultrasonographic recurrence, clinical recurrence only being taken into account: its percentage ranges from 10 to 20%, increasing with the time lapse after thyroidectomy. Attempts to prevent recurrence are based on an approach of the physiopathology of thyroid nodules. Clinical and epidemiological studies of patients with goiters suggest that TSH may play a role in the generation of goiters, as has been confirmed by experimental work. However, several other local autocrine or paracrine growth factors may also be involved in the generation of goiters, including IGF I and IGF II (Insulin Growth Factors), FGF (Fibroblast Growth Factor), EGF (Epidermal Growth Factor), TGFB (Transforming Growth Factor beta). On the basis of the possible role of TSH in goiter generation, some teams have advocated a postoperative course of thyroid hormones aimed at limiting thyreostimulin production. These studies, most of them retrospective studies, do not allow drawing a meaningful conclusion because their methods are open to criticism and the results observed are disparate. On a whole, although thyroid hormone therapy is often used after hemithyroidectomy, the physiopathological bases of its prescription are disputable, and the results obtained in terms of recurrence of nodules are not conclusive enough. It is therefore desirable to set up randomized studies.

Humans↗

PubMed1992

[Screening and prevention of type 1 diabetes].

Insulin-dependent diabetes mellitus is preceded by a prodromal phase during which insulin-secreting cells are progressively destroyed by immunological factors. Among genetically predisposed and high risk subjects, this phase of prediabetes can be identified by detection of immunological and metabolic markers. For these prediabetic subjects, specific immunomodulators, without adverse effect, will be available.

Biomarkers↗