SummaryInsulin-dependent diabetes mellitus (IDDM) is associated with autoreactivity against GAD but the diagnostic sensitivity (positivity in disease) and specificity (negativity in health) of isoform-specific GAD antibodies have yet to be defined in assay systems suitable for screening large number of samples. One set of IDDM patient (n = 10) and control (n = 50) standard sera were used to develop quantitative antibody assays with in vitro synthesized recombinant 35S-methionine-labelled GAD65 and GAD67, respectively, and protein A-Sepharose to separate free from antibody-bound ligand. Binding levels were not normally distributed (p < 0.0001) and therefore, the diagnostic accuracy of GAD antibodies was analysed by the ROC plots in population-based, consecutively-diagnosed, recent onset, 0-14year-old patients (n = 105), and matched, healthy control subjects (n = 157). The ROC plots showed that the diagnostic sensitivity of GAD65 antibodies was 77 % and the specificity 92 % compared with 8 % and 98 %, respectively for GAD67 antibodies. In the IDDM sera, GAD65 and GAD67 antibodies were concordant in 7% (6 of 81) and GAD65 antibodies and ICA in 89 % (72 of 81) without a correlation between the autoantibody levels. Autoantibodies to recombinant human islet GAD65 are specific and sensitive markers for childhood IDDM in this immunoassay with in vitro synthesized 35S-methioninelabelled recombinant GAD. [Diabetologia (1994) Abbreviations: IDDM, insulin-dependent diabetes mellitus; GAD, glutamic acid decarboxylase; ROC, receiver-operating characteristic; ICA, islet cell antibodies; JDF, Juvenile Diabetes Foundation 10p11.3-p12 [7]. GAD65 shows 65 % amino acid identity with GAD67, the isoform coded for by the GAD1 gene on chromosome 2q31 [7][8][9]. The molecular cloning of full-length human islet GAD65 [7] and rat islet GAD67 [10] cDNA has made it possible to demonstrate autoreactivity in diabetes to the recombinant proteins in both eukaryotic [11,12] and bacterial [13] expression systems. GAD65 (but not GAD67) is expressed in human islets [11,14], however, variable reactivity of patient sera has been reported [12,13,[15][16][17][18][19]. GAD65 specificity of IDDM sera was first demonstrated in our immunoprecipitation assay with recombinant GAD expressed in transfected cells [12] and recently confirmed in other assays with recombinant antigens [18,20]. The use of different assay systems and species-specific GAD65 and GAD67 may explain the lower frequency of GAD67 antibodies in these compared to previous reports [13,16]. We now report the

The mechanisms by which the beta cells of pancreatic islets are destroyed in insulin-dependent diabetes mellitus (IDDM) are poorly understood. In this report the pancreatic histo- and immunopathology of two children, both HLA-DR 3/4, DQ 2/8 positive and who both died from cerebral oedema within a day of clinical diagnosis of IDDM, were investigated. Patient 1, a 14-month-old girl, had a 4-week history of polydipsia and polyuria. Patient 2, a 3-year-old boy, had 2 days of illness. Both patients had a similarly severe loss of insulin cells but differed markedly as to the extent of lymphocytic islet infiltration (insulitis). Apart from insulitis, marked islet macrophage infiltration was demonstrated in both patients with the HAM-56 monoclonal antibody. Neither patient showed aberrant expression of HLA class II antigens on insulin-immunoreactive cells, but allele-specific HLA-DQ8 expression was evident on endothelial cells. Glutamic acid decarboxylase immunoreactivity was detected in both insulin- and glucagon-immunoreactive cells. It is concluded that the heterogeneity of islet pathology, especially insulitis, may reflect different dynamics and extent rather than different pathomechanisms of immune destruction of islets in IDDM.

With the advent of the microwave radiometer, passive remote sensing of clouds and precipitation has become an indispensable tool in a variety of meteorological and oceanographical applications. There is wide interest in the quantitative retrieval of water vapor, cloud liquid, and ice using brightness temperature observations in scientific studies such as earth's radiation budget and microphysical processes of winter and summer clouds. Emission and scattering characteristics of hydrometeors depend on the frequency of observation. Thus, a multifrequency radiometer has the capability of profiling cloud microphysics. Sensitivities of vapor, liquid, and ice with respect to 20.6, 31.65 and 90 GHz brightness temperatures are studied. For the model studies, the atmosphere is characterized by vapor density and temperature profiles and layers of liquid and ice components. A parameterized radiative transfer model is used to quantify radiation emanating from the atmosphere. It is shown that downwelling scattering of radiation by an ice layer results in enhancement at 90 GHz brightness temperature. Once absorptive components such as vapor and liquid are estimated accurately, then it is shown that the ice water path can be retrieved using ground-based three-channel radiometer observations. In this paper we developed two-and three-channel neural network-based inversion models. Success of a neural network-based approach is demonstrated using a simulated time series of vapor, liquid, and ice. Performance of the standard explicit inversion model is compared with an iterative inversion model. In Part II of this paper, actual radiometer, and radar field measurements are utilized to show practical applicability of the inverse models. I. INTRODUCTION G ROUND-BASED dual-channel radiometers have been used successfully for more than 20 years to monitor vapor and cloud water [1]-[4]. Radiometric measurements of total precipitable water vapor column are about the same as, or better than, those of radiosondes [3]. Retrievals from groundbased radiometers are also used as a validation for satellite sensors. Unlike radiosondes, radiometers provide measurements unattendedly and continuously. Westwater [1] and Staelin [5]