Cytoplasmic islet cell antibodies recognize distinct islet antigens in IDDM but not in stiff man syndrome

Cytoplasmic islet cell antibodies are well-established predictive markers of IDDM. Although target molecules of ICA have been suggested to be gangliosides, human monoclonal ICA of the immunoglobulin G class (MICA 1-6) produced from a patient with newly diagnosed IDDM recognized glutamate decarboxylase as a target antigen. Here we analyzed the possible heterogeneity of target antigens of ICA by subtracting the GAD-specific ICA staining from total ICA staining of sera. This was achieved 1) by preabsorption of ICA+ sera with recombinant GAD65 and/or GAD67 expressed in a baculovirus system and 2) by ICA analysis of sera on mouse pancreas, as GAD antibodies do not stain mouse islets in the immunofluorescence test. We show that 24 of 25 sera from newly diagnosed patients with IDDM recognize islet antigens besides GAD. In contrast, GAD was the only islet antigen recognized by ICA from 7 sera from patients with stiff man syndrome. Two of these sera, however, recognized antigens besides GAD in Purkinje cells. In patients with IDDM, non-GAD ICA were diverse. One group, found in 64% of the sera, stained human and mouse islets, whereas the other group of non-GAD ICA was human specific. Therefore, mouse islets distinguish two groups of non-GAD ICA and lack additional target epitopes of ICA besides GAD. Longitudinal analysis of 6 sera from nondiabetic ICA+ individuals revealed that mouse-reactive ICA may appear closer to clinical onset of IDDM in some individuals

Statistical analysis of the Central-Europe Seismicity

The aim of this paper is to characterize the spatio-temporal distribution of Central-Europe seismicity. Specifically, by using a non-parametric statistical approach, the proportional hazard model, leading to an empirical estimation of the hazard function, we provide some constrains on the time behavior of earthquake generation mechanisms. The results indicate that the most conspic- uous characteristics of MW 4.0+ earthquakes is a temporal clustering lasting a couple of years. This suggests that the probability of occurrence increases immediately after a previous event. After a few years, the process becomes almost time independent. Furthermore, we investigate the cluster properties of the seismicity of Central-Europe, by comparing the obtained result with the one of synthetic catalogs generated by the epidemic type aftershock sequences (ETAS) model, which previously have been successfully applied for short term clustering. Our results indicate that the ETAS is not well suited to describe the seismicity as a whole, while it is able to capture the features of the short- term behaviour. Remarkably, similar results have been previously found for Italy using a higher magnitude threshold

Antibodies to the Mr 64,000 (64K) protein in islet cell antibody positive non-diabetic individuals indicate high risk for impaired Beta-cell function

A prospective study of a normal childhood population identified 44 islet cell antibody positive individuals. These subjects were typed for HLA DR and DQ alleles and investigated for the presence of antibodies to the Mr 64,000 (64K) islet cell antigen, complement-fixing islet cell antibodies and radiobinding insulin autoantibodies to determine their potency in detecting subjects with impaired Beta-cell function. At initial testing 64K antibodies were found in six of 44 islet cell antibody positive subjects (13.6%). The same sera were also positive for complement-fixing islet cell antibodies and five of them had insulin autoantibodies. During the follow-up at 18 months, islet cell antibodies remained detectable in 50% of the subjects studied. In all six cases who were originally positive, 64K antibodies were persistently detectable, whereas complement-fixing islet cell antibodies became negative in two of six and insulin autoantibodies in one of five individuals. HLA DR4 (p < 0.005) and absence of asparic acid (Asp) at position 57 of the HLA DQ chain (p < 0.05) were significantly increased in subjects with 64K antibodies compared with control subjects. Of 40 individuals tested in the intravenous glucose tolerance test, three had a first phase insulin response below the first percentile of normal control subjects. Two children developed Type 1 (insulin-dependent) diabetes mellitus after 18 and 26 months, respectively. Each of these subjects was non-Asp homozygous and had persistent islet cell and 64K antibodies. We conclude that 64K antibodies, complement-fixing islet cell antibodies and insulin autoantibodies represent sensitive serological markers in assessing high risk for a progression to Type 1 diabetes in islet cell antibody positive non-diabetic individuals

Violence as an Under-Recognized Barrier to Women’s Realization of Their Right to Adequate Food and Nutrition: Case Studies From Georgia and South Africa

This article addresses under-acknowledged barriers of structural violence and discrimination that interfere with women’s capacity to realize their human rights generally, and their right to adequate food and nutrition in particular. Case studies from Georgia and South Africa illustrate the need for a human rights–based approach to food and nutrition security that prioritizes non-discrimination, public participation, and self-determination. These principles are frustrated by different types of structural violence that, if not seriously addressed, pose multiple barriers to women’s economic, public, and social engagement. </jats:p

Dissociating sub-processes of aftereffects of completed intentions and costs to the ongoing task in prospective memory: A mouse-tracking approach

In the present study, we used mouse tracking to investigate two processes underlying prospective memory (PM) retrieval: First, we aimed to explore to what extent spontaneous retrieval of already completed PM intentions is supported by reflexive-associative and discrepancy-plus-search processes. Second, we aimed to disentangle whether costs to an ongoing task during the pursuit of a PM intention are associated with presumably resource-demanding monitoring processes or with a presumably resource-sparing strategic delay of ongoing-task responses. Our third aim was to explore the interaction of processes underlying costs to the ongoing task and processes of spontaneous retrieval. Our analyses replicated response-time patterns from previous studies indicating aftereffects of completed intentions and costs to ongoing-task performance, as well as increased aftereffects while pursuing a PM intention. Notably, based on our mouse-tracking analyses, we argue that aftereffects of completed intentions are best explained by a reflexive initiation of an already completed intention. If the completed intention is not performed in its entirety (i.e., no commission error), the reflexive initiation of the completed intention is followed by a subsequent movement correction that most likely represents a time-consuming response-verification process. Regarding performance costs in the ongoing task, our analyses suggest that actively pursuing a PM intention most likely leads to a strategic delay of ongoing activities. Lastly, we found that pursuing a novel PM task after intention completion exacerbated orienting responses to all deviant stimuli, exacerbated the readiness to initiate the completed intention reflexively, and substantially prolonged the response-verification process following this reflexive intention retrieval

Epidemiology and immunogenetic background of islet cell antibody - positive nondiabetic schoolchildren : Ulm-Frankfurt population study

Islet cell antibodies (ICAs) were determined in a large cohort of white nondiabetic schoolchildren (n = 4287) from a homogenous population in southern Germany. The prevalence of ICA levels greater than or equal to 5 Juvenile Diabetes Foundation (JDF) U was 1.05% (95% confidence interval 0.8-1.4%). Analysis of HLA-DR beta and -DQ beta alleles revealed that the specificities found to be increased in insulin-dependent (type I) diabetic subjects with the same ethnic background were also associated with ICA positivity in the nondiabetic schoolchildren. HLA-DR3 (P less than 0.01) and -DR4 (P less than 0.01) phenotypes and absence of Asp residue (P less than 0.01) at codon 57 of the HLA-DQ beta-chain were significantly increased in ICA+ compared with control subjects. High levels of ICAs, which were categorized as either greater than or equal to 17 or greater than or equal to 30 JDF U, were found to be associated with amino acids other than Asp at position 57 of the HLA-DQ beta-chain. No association of ICA level was found for HLA-DR phenotypes

Ambient vibration measurements in the Southern Rhine Graben close to Basle

This study presents results of ambient noise measurements from temporary single station and small-scale array deployments in the northeast of Basle. H/V spectral ratios were determined along various profiles crossing the eastern masterfault of the Rhine Rift Valley and the adjacent sedimentary rift fills. The fundamental H/V peak frequencies are decreasing along the profile towards the eastern direction being consistent with the dip of the tertiary sediments within the rift. Using existing empirical relationships between H/V frequency peaks and the depth of the dominant seismic contrast, derived on basis of the ?/4-resonance hypothesis and a power law depth dependence of the S-wave velocity, we obtain thicknesses of the rift fill from about 155 m in the west to 280 m in the east. This is in agreement with previous studies. The array analysis of the ambient noise wavefield yielded a stable dispersion relation consistent with Rayleigh wave propagation velocities. We conclude that a significant amount of surface waves is contained in the observed wavefield. The computed ellipticity for fundamental mode Rayleigh waves for the velocity depth models used for the estimation of the sediment thicknesses is in agreement with the observed H/V spectra over a large frequency band

Association between Antibodies to the MR 67,000 Isoform of Glutamate Decarboxylase (GAD) and Type 1 (Insulin-Dependent) Diabetes Mellitus with Coexisting Autoimmune Polyendocrine Syndrome Type II

By using an immunoprecipitation assay, we analysed reactivity of autoantibodies to human recombinant GAD65 and GAD67 in sera from patients with autoimmune polyendocrine syndrome Type II (APS II) with and without Type 1 (insulin-dependent) diabetes mellitus (IDDM) compared to patients with organ-specific autoimmunity. Overall antibodies to GAD65 were correlated with IDDM in all study groups, whereas GAD67 antibodies were associated with IDDM when APS II coexists. Antibodies to GAD65 and GAD67 were detected in 13 (44.8%) and 7 (24.1%) out of 29 APS II patients with IDDM, but in only 4 (13.8%) and 2 (6.9%) out of 29 APS II patients without IDDM, respectively (p < 0.05). In short-standing IDDM (< 1 year), antibodies to GAD67 were significantly more frequent in patients with APS II (5 of 9 [55.6%] subjects) compared to matched diabetic patients without coexisting polyendocrinopathy (1 of 18 [5.6%] subjects) (p < 0.02). The levels of GAD65 (142 ± 90 AU) and GAD67 antibodies (178 ± 95 AU) were significantly higher in patients with polyglandular disease than in patients with isolated IDDM (91 ± 85 AU and 93 ± 57 AU) (p < 0.02). Interestingly, all 11 GAD67 antibody positive subjects also had GAD65 antibodies (p < 0.0001), and in 10 of 11 anti-GAD67 positive sera the GAD67 antibodies could be blocked by either GAD67 or GAD65, suggesting the presence of cross-reactive autoantibodies. No correlation was observed between GAD antibodies and age, sex or any particular associated autoimmune disease, besides IDDM. GAD antibodies were present in only 1 of 6 (16.7%) patients with APS Type I, in 1 of 26 (3.9%) patients with autoimmune thyroid disease but in none of the patients with Addison's disease (n = 16), pernicious anaemia (n = 7) or normal controls (n = 50). Our data suggest distinct antibody specificities reactive to GAD isoforms in APS II and IDDM, which might reflect different mechanisms of autoimmune response in IDDM with coexisting autoimmune polyendocrine autoimmunity

Expectancy effects in the EEG during joint and spontaneous word-by-word sentence production in German

Our aim in the present study is to measure neural correlates during spontaneous interactive sentence production. We present a novel approach using the word-by-word technique from improvisational theatre, in which two speakers jointly produce one sentence. This paradigm allows the assessment of behavioural aspects, such as turn-times, and electrophysiological responses, such as event-related-potentials (ERPs). Twenty-five participants constructed a cued but spontaneous four-word German sentence together with a confederate, taking turns for each word of the sentence. In 30% of the trials, the confederate uttered an unexpected gender-marked article. To complete the sentence in a meaningful way, the participant had to detect the violation and retrieve and utter a new fitting response. We found significant increases in response times after unexpected words and – despite allowing unscripted language production and naturally varying speech material – successfully detected significant N400 and P600 ERP effects for the unexpected word. The N400 EEG activity further significantly predicted the response time of the subsequent turn. Our results show that combining behavioural and neuroscientific measures of verbal interactions while retaining sufficient experimental control is possible, and that this combination provides promising insights into the mechanisms of spontaneous spoken dialogue

Insulin autoantibodies as determined by competitive radiobinding assay are positively correlated with impaired beta-cell function — The Ulm-Frankfurt population study

Out of a random population of 4208 non-diabetic pupils without a family history of Type I diabetes 44 (1.05%) individuals had islet cell antibody (ICA) levels greater or equal to 5 Juvenile Diabetes Foundation (JDF) units. 39 of these ICA-positives could be repeatedly tested for circulating insulin autoantibodies (CIAA) using a competitive radiobinding assay. The results were compared with the insulin responses in the intravenous glucose tolerance tests (IVGTT) and with HLA types. Six pupils were positive for CIAA. All of them had complement-fixing ICA, and 5 of them were HLA-DR4 positive. Three of the 6 showed a first-phase insulin response below the first percentile of normal controls. Our data indicate that in population-based studies CIAA can be considered as a high risk marker for impaired beta-cell function in non-diabetic ICA-positive individuals