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.     

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.     

Paternal mosaicism for a novel PBX1 mutation associated with recurrent perinatal death: Phenotypic expansion of the PBX1‐related syndrome

Autosomal dominant (de novo) mutations in PBX1 are known to cause congenital abnormalities of the kidney and urinary tract (CAKUT), with or without extra‐renal abnormalities. Using trio exome sequencing, we identified a PBX1 p.(Arg107Trp) mutation in a deceased one‐day‐old neonate presenting with CAKUT, asplenia, and severe bilateral diaphragmatic thinning and eventration. Further investigation by droplet digital PCR revealed that the mutation had occurred post‐zygotically in the father, with different variant allele frequencies of the mosaic PBX1 mutation in blood (10%) and sperm (20%). Interestingly, the father had subclinical hydronephrosis in childhood. With an expected recurrence risk of one in five, chorionic villus sampling and prenatal diagnosis for the PBX1 mutation identified recurrence in a subsequent pregnancy. The family opted to continue the pregnancy and the second affected sibling was stillborn at 35 weeks, presenting with similar severe bilateral diaphragmatic eventration, microsplenia, and complete sex reversal (46, XY female). This study highlights the importance of follow‐up studies for presumed de novo and low‐level mosaic variants and broadens the phenotypic spectrum of developmental abnormalities caused by PBX1 mutations.     

LPS stimulated invertebrate hemocytes: a role for immunoreactive TNF and IL-1

Mytilus edulis hemocytes have similarities with vertebrate monocyte/macrophages. We have recently shown that they respond to human TNF and IL-1. We tested the possibility that Mytilus hemocytes produce similar substances in response to LPS. We show that Mytilus hemocytes respond to LPS in a fashion similar to vertebrate monocytes and macrophages and that these responses are inhibited by antibodies to TNF and/or IL-1. These findings are demonstrated both in vitro and in vivo.     

The effects of carnosine on oxidative DNA damage levels and in vitro lifespan in human peripheral blood derived CD4+T cell clones

Carnosine (beta-alanyl-L-histidine), an abundant naturally-occurring dipeptide has been shown to exhibit anti-ageing properties towards cultured cells, possibly due in part to its antioxidant/free radical scavenging abilities. In this paper the results of an investigation on the effects of carnosine, at the physiological concentration of 20 mM, on oxidative DNA damage levels and in vitro lifespan in peripheral blood derived human CD4+ T cell clones are reported. Under the culture conditions used (20% O(2)) long term culture with carnosine resulted in a significant increase in the lifespan of a clone derived from a healthy young subject. No such extension was observed when a T cell clone from a healthy old SENIEUR donor was similarly cultured. Culture with carnosine from the midpoint of each clone's lifespan did not have any effect on longevity, independent of donor age. Oxidative DNA damage levels were measured in the clones at various points in their lifespans. Carnosine acted as a weak antioxidant, with levels of oxidative DNA damage being lower in T cells grown long term in the presence of carnosine. The possibility that carnosine might confer anti-ageing effects to T cells under physiological oxygen tensions would appear to be worthy of further investigation.     

Multiplicity of allergens in peanuts

Crude peanut protein fractions from raw and roasted peanuts were examined in the RAST with 10 sera from patients showing clinical peanut sensitivity. The radioactive uptake results, which were generally high, did not reveal any distinguishable pattern. Two commercially available peanut proteins, peanut lectin and phospholipase D, gave poor RAST responses. Three purified peanut proteins, α-arachin, conarachin I, and concanavalin A-reactive glycoprotein, all gave significant RAST results that were generally lower than those obtained with the crude extracts. The extent of RAST inhibition obtained with these materials was inversely related to their abundance in the total peanut protein. Crossed immunoelectrophoresis with extracts from raw and roasted peanut indicated the presence of 22 and 10 anodically migrating antigens, respectively. Sixteen IgE binding antigens were revealed for raw peanut and seven for roasted peanut after incubation with a mixed serum from the 10 patients in crossed radioimmunoelectrophoresis (CRIE) using ¹²⁵I-labeled anti-IgE. CRIE plates treated with individual serum samples showed that all the patients had specific IgE for the major antigen peak, which has been tentatively identified as α-arachin. This major storage protein of peanut, which is known to be particularly heat resistant, may be of greater clinical significance than its apparently low RAST activity would seem to indicate.     

CT metrizamide myelography in syringomyelia: sensitivity and specificity

In a retrospective study of 32 patients with "proven" syringomyelia and 15 patients with an alternate proven diagnosis, a change in the caliber of the spinal cord with different positions ("collapsing cord sign or cord collapse") had a sensitivity of 38% and a specificity of 87%. Central cord enhancement ("bull's-eye") on delayed CT had a sensitivity and specificity of 91% and 87%, respectively. The positive predictive value of cord collapse was 87%, while the positive predictive value of central cord enhancement was 94%.