Biomedical subjects

A Toivonen

Publications and source records attributed to A Toivonen.

7 recordsLinked to original sources

PubMed2006

IA-2 antibody isotypes and epitope specificity during the prediabetic process in children with HLA-conferred susceptibility to type I diabetes.

The natural history of preclinical diabetes is partly characterized, but there is still limited information on the dynamics of the immune response to beta-cell autoantigens during the course of preclinical disease. The aim of this work was to assess the maturation of the humoral immune response to the protein tyrosine phosphatase(PTP)-related proteins (IA-2 and IA-2beta) in preclinical type I diabetes (TID). Forty-five children participating in the Finnish Type I Diabetes Prediction and Prevention (DIPP) Study who had seroconverted to IA-2 antibody positivity were analysed. Specific radiobinding assays were used to determine IA-2/IA-2beta epitope-specific antibodies (the juxtamembrane (JM) region of IA-2, PTP-like domain and betaPTP-like domain) and isotype-specific IA-2 antibodies. Individual areas under the curve (AUC) over the observation period were calculated for total IA-2 antibodies, each isotype and specific epitope responses. The children who progressed to TID tended to have an initial IA-2 JM epitope response more frequently (P = 0.06), and this response was more often dominant during the observation period (P < 0.05). The children who did not progress to TID had IgE-IA-2 more frequently (70%; versus progressors 27%; P < 0.05), and had higher integrated titres of IgE-IA-2 antibodies (P < 0.05). The occurrence of IgE-IA-2 antibodies was protective even when combined with positivity for IA-2 JM antibodies (P = 0.002). IgE-IA-2 antibody reactivity may be a marker of a regulatory immune response providing protection against or delaying progression to TID among IA-2 antibody-positive young children with HLA-conferred disease susceptibility.

Autoantibodies↗

PubMed2001

No evidence of abnormal regulation of antibody response to coxsackievirus B4 antigen in prediabetic children.

Enterovirus infections are a potential environmental trigger of the autoimmune process leading to clinical type 1 diabetes. It has been suggested that the risk of virus-induced beta-cell damage might be connected with a defect in humoral immune responsiveness to enteroviruses. In the present study we assessed whether such a defect in IgG responsiveness to coxsackievirus B4 antigen existed in young children who developed diabetes-associated autoantibodies during prospective observation from birth until the age of 18 months. IgG levels and maturation of antibody avidity were analysed in 21 children with autoantibodies and 41 control children who had experienced an equal number of enterovirus infections and were additionally matched for age, sex and HLA-DQB1 risk alleles for type 1 diabetes but had not produced diabetes-associated autoantibodies. IgG levels to coxsackievirus B4 were high in cord serum reflecting the presence of maternal antibodies. Mean IgG levels gradually decreased but began to increase after the age of 6 months, showing no significant difference between autoantibody positive and control children. The avidity of antibodies was strong in cord serum and decreased gradually during the first year of life when maternal antibodies disappeared. The avidity indices, which varied considerably from child to child, did not differ between the autoantibody-positive and -negative subjects. In conclusion, our data suggest that children affected by a beta-cell damaging autoimmune process show normal responses to coxsackievirus B4 antigens.

Antibodies, Viral↗

PubMed2001

Soluble adhesion molecules in preclinical type 1 diabetes. The Childhood Diabetes in Finland Study Group.

We measured the concentrations of the soluble forms of the intercellular adhesion molecule-1 (sICAM-1) and L-selectin in 95 autoantibody-positive siblings of children with type 1 diabetes and 95 sex- and age-matched siblings testing negative for diabetes-associated autoantibodies to assess the possible role of soluble adhesion molecules as markers of progressive ss-cell destruction in preclinical diabetes and their ability to discriminate between those siblings who progress to clinical disease and those who remain nondiabetic. We observed an inverse correlation between age and the levels of both sICAM-1 (r = -0.31, p < 0.001) and sL-selectin (r = -0.27, p < 0.001) in the control siblings but no association with HLA-DR phenotypes. There was no difference in the circulating levels of soluble adhesion molecules between the antibody-positive and negative siblings. Among the antibody-positive siblings, those with at least three autoantibodies had higher sICAM-1 levels (p < 0.01) than those testing positive for only one, and siblings with three autoantibodies or more had higher concentrations of sL-selectin (p < 0.01) than those with two autoantibodies. Siblings with an islet cell antibody level of 20 Juvenile Diabetes Foundation units or more had higher sICAM-1 concentrations than those with a level below 20 (p < 0.001), and those testing positive for antibodies to the protein tyrosine phosphatase-related IA-2 antigen had increased levels of both sICAM-1 (p = 0.03) and sL-selectin (p = 0.02) compared with siblings who tested negative. The antibody-positive siblings who progressed to clinical type 1 diabetes were significantly younger than the nonprogressors (p < 0.001) and had higher levels of sICAM-1 initially (p < 0.001). The difference in sICAM-1 concentrations remained significant (p = 0.03) after age adjustment. Our results indicate that concentrations of soluble adhesion molecules are increased in the autoantibody-positive siblings who have the highest risk of developing clinical diabetes, suggesting that ss-cell destruction is reflected in increased circulating levels of these molecules. This is supported by the observation of elevated sICAM-1 concentrations in the 29 siblings who actually progressed to clinical type 1 diabetes. Peripheral levels of soluble adhesion molecules are not able to discriminate between progressors and nonprogressors, however, due to substantial overlapping between these two groups.

Adolescent↗

PubMed1994

Caries development after substitution of supervised fluoride rinses and toothbrushings by unsupervised use of fluoride toothpaste.

In a nonfluoridated community of Finland, where fortnightly fluoride rinsing with 0.2% sodium fluoride has been used for nearly two decades, a total of 313 children 7-8 yr old were recruited and randomly divided into two groups. 206 children completed the 3-yr trial. The control group (n = 94) participated in the rinsing program which included supervised toothbrushings, while the test group (n = 112) received a new fluoride toothpaste tube (0.15% F) for home use every second month. Annual dental recordings, treatment plannings and the treatment itself were all carried out by one clinician. At the end of the study the number of caries-free children of the toothpaste group was lower (P < 0.01) and the caries increment higher (P < 0.05) than that of the mouthrinse group. Out of the mean of four dental visits per child and year some 1.5 were prophylactic by nature. No differences were found between the number of treatment visits, time or prophylactic care of the two groups. Unsupervised use of fluoride toothpaste may not be a sufficient substitute for the school-based fortnightly fluoride rinses and supervised toothbrushings in caries prevention of children with erupting permanent teeth.

Child↗

PubMed1993

Depletion of Langerhans cells in cervical HPV infection is associated with replication of the virus.

We studied the quantity of Langerhans cells in 36 patients with cervical human papillomavirus (HPV) infection. Significantly fewer Langerhans cells (p < 0.05) were found in patients with compared to those without DNA tetraploidy. Similarly, patients positive for HPV 16/18 DNA by in situ hybridization or antipeptide IgA antibodies to HPV 18 tended to have fewer Langerhans cells than those negative for HPV 16/18 DNA or IgA antibodies. Our results suggest that depletion of Langerhans cells is associated with productive HPV 16/18 infection in the cervical epithelium.

Antibodies, Viral↗

PubMed1979

Effect of caries in mentally handicapped children of addition of fluoride and bicarbonate-phosphate to dietary sugar products.

Mentally handicapped children, aged 5--15 years and living in institutions, received fluoride supplement in several sugar products of their diet; in candies, marmalades, jams, fruit juices and in sweet desserts corresponding to 10 mg F as NaF per kg of the sugar (sucrose or glucose) of each product. To two of the four daily candies was also added a NaHCO3 + KH2PO4 mixture (mole ratio 9.8/l, resp.) to substitute for 2.5% of the sugar of the candy. The control children received the respective products without the additives. After stepwise exclusions of subjects for various reasons, e.g. for the absence of permanent teeth, low initial caries activity, strong medication, Down's syndrome, etc., the mean DMFS-increment in the remaining 43 control subjects was 4.5 and in the 41 test subjects 2.6 lesions/100 surfaces at risk, i.e. 42% reduction. Caries arrestment had occurred in these test subjects after the first year, while in the respective controls it was continuously increasing. Among numerous oral and body parameters studied, only surface enamel fluoride in primary teeth was increased by the fluoride supplements and urinary phosphate and calcium excretion decreased.

Adolescent↗

PubMedDate not supplied

Influence of coupling method on the luminescence properties, coupling efficiency, and binding affinity of antibodies labeled with europium (III) chelates.

A series of chelating 4-(phenylethynyl)pyridines having various 1,3,5-triazin-2-ylamino groups at the para position of the phenyl ring was synthesized. Their europium chelates were coupled to antibodies and the properties of antibody conjugates analyzed by fluorometry and in time-resolved fluorometric immunoassay. The substituents in the triazine ring were observed to have various effects on the chelate luminescence, the labeling properties of the chelates, and the immunoreactivity of labeled antibodies. The series of substituted triazinyl derivatives serves as a model of bioreactive groups that can be applied when certain properties are searched for, such as improved chelate solubilities, minimized internal quenching, different effects on the ligand triplet state, and stipulated coupling reactivities.

Antibodies↗