The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell- mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ- specific autoimmune disease.      

Coat protein of potyviruses 7. Amino acid sequence of peanut stripe virus

Summary The amino acid sequence of the 287-residue coat protein of peanut stripe virus (PStV) was determined from the sequences of overlapping peptide fragments. Results indicated that the amino terminus was blocked by an acetyl group, as has previously been found for the coat protein of Johnsongrass mosaic potyvirus. Comparison of the PStV sequence with coat proteins of 20 distinct potyviruses gave sequence identities of 47–57%, except for zucchini yellow mosaic virus (ZYMV), passionfruit woodiness virus (PWV), and the related strains watermelon mosaic virus 2 (WMV 2) and soybean mosaic virus-N, which showed sequence identities of 70–76%. Several amino acid residues which were common to the core sequences of these coat proteins were at positions previously found to be invariant among potyvirus coat proteins. The degree of these similarities suggests that although PStV, WMV 2, ZYMV, and PWV are distinct potyviruses, they share a common ancestor in their evolutionary development.     

An investigation of Japanese subjects maps susceptibility to type 1 (insulin-dependent) diabetes mellitus close to the DQA1 gene.

Insulin-dependent diabetic and control subjects of Japanese origin were HLA-DRB1, -DQB1, and -DQA1 typed using restriction fragment length polymorphism analysis and sequence-specific oligonucleotide gene probing. The DQA1 allele DQA1*0301 was positively associated with the disease [48/52 (92%) diabetic patients versus 44/64 (69%) control subjects, Pc less than 0.03, RR = 4.97]. Alleles of the DRB1 and DQB1 genes showed no significant association with the disease. The frequency of DQB1 genotypes encoding the amino acid aspartic acid at position 57 of the DQ beta chain did not differ significantly between subjects with insulin-dependent diabetes mellitus (IDDM) and controls. These findings suggest that a susceptibility allele for IDDM in the Japanese is more closely associated with the DQA1 gene than the DQB1 gene.     

The nucleotide sequence of two new DP alleles, DPA1*02015 and DPB1*8401, identified in a Chinese subject

The HLA-DP genes (HLA-DPA1 and -DPB1) are encoded by the major histocompatibility complex (MHC) on human chromosome 6. They are involved in the presentation of antigen to CD4+ T cells as part of the class II antigen-presentation pathway. During a small study of Oriental subjects (11 Chinese and 26 Japanese subjects), one Chinese subject was identified as having numerous heterozygous sites within the second exon of both DPA1 and DPB1. These were further analysed using novel codon-specific primers. Sequencing analysis using these primers determined the subject to have DPA1*0103/*02015 and DPB1*0501/*8401; these new alleles have been submitted to GenBank and assigned the accession numbers AF098794 and AF077015, respectively.     

Effects of incentive items on participation in a randomized chemoprevention trial

Behavioral research has an important role in increasing and maintaining participation in disease prevention trials, both in interventions and in follow-up visits. We conducted a randomized experiment among participants in the lung cancer chemoprevention trial, CARET (Carotene and Retinol Efficacy Trial) to test the effects of providing two incentives on retention. The items used for this study were a Certificate of Appreciation and one of two lapel pins, provided in a 2 2 design. Providing incentives, whether alone or in combination, had no statistically significant effect on retention by the two-year follow-up point. The successful implementation of this randomized incentive study has two implications for future research: (1) study of behavioral interventions and issues is feasible in the context of large controlled trials of disease end-points; and (2) such study is necessary to determine whether selected incentives can increase retention.     

An investigation of visuospatial memory impairment in children with attention deficit hyperactivity disorder (ADHD), combined type

BACKGROUND: Memory impairment is not considered a core cognitive feature of attention deficit hyperactivity disorder, combined type (ADHD-CT), although it is associated with impairments in attentional and executive functions. This study investigates visuospatial memory impairment, in particular encoding and retrieval aspects, in children with ADHD-CT who are stimulant-medication naive and medicated with stimulant medication. METHOD: A cross-sectional study of visuospatial memory in 6- to 12-year-old children with stimulant-medication-naive ADHD-CT (n = 62) and medicated ADHD-CT (n = 58) compared to an age- and gender-matched healthy control group (n = 39) was completed. RESULTS: Both medication-naive and medicated ADHD-CT groups demonstrated subtle yet significant impairment in visuospatial memory. The memory impairment was delay-independent, which, along with other factors, suggest dysfunction of the encoding rather than retrieval phase of visuospatial memory. CONCLUSIONS: Careful study of large ADHD-CT samples does detect deficits in a visuospatial memory task, but these reflect attentional deficits rather than being specifically due to dysfunction of the medial temporal lobe explicit memory system. Children with ADHD-CT may benefit from cognitive and behavioural strategies focused on improving encoding of relevant information rather than retrieval strategies.     

Immune response of New Zealand mice to trinitrophenylated syngeneic mouse red cells.

NZB and NZB/W mice have reduced anti-sheep red cell (SRC) and 2,4,6-trinitrophenyl-plaque-froming cell (TNP-PFC) responses with age after injection of either the thymus-dependent antigen TNP-SRC or the thymus-independent antigen TNP-mouse red cells (MRC). However, the thymus-dependent response diminished much faster than the thymus-independent response. As a consequence, young New Zealand mice have a higher anti-TNP response after injection of TNP-SRC than after injection of TNP-MRC, while old New Zealand mice have a higher anti-TNP response after injection of TNP-MRC than after injection of TNP-SRC. The PFC avidity of NZB/W mice injected with TNP-SRC diminished with age, while the PFC avidity of mice injected with TNP-MRC did not change with agrc or TNP-SRC. Old NZB/W mice had few spontaneous anti-MRC-PFC. The number of anti-MRC PFC in old mice was increased 4 to 10 times after injection with either TNP-SRC or TNP-MRC. It is suggested that surveillance mechanisms are responsible for suppressing the autoimmune response to modified self-antigens. The unregulated immune system of NZB and NZB/W mice appears to be an expression of impairment of such a hypothetical surveillance mechanism.     

Allergens in the white and yolk of hen's egg. A study of IgE binding by egg proteins

The radioallergosorbent test (RAST) was used to compare the IgE binding of egg white and yolk, and allergenic proteins were detected by immunoelectrotransfer ('Western blotting'). The main allergens were found in egg white, but for a large proportion of the egg-sensitive patients, yolk contained specific IgE-binding constituents. For blood sera from 36 patients, there was a positive correlation between the results of RAST for egg white and for yolk. Lysozyme was found to be an allergen for some patients. The effect of heating on the allergenicity of egg white was examined and the allergenicity of hen egg white was compared with that of a duck egg. The allergens in yolk were associated with each of the three yolk fractions, and several of the proteins in the low-density lipoprotein fraction bound IgE.