Auto-agglutination in albumin

An example of the `albumin' auto-agglutinating phenomenon is reported. This was found in the serum of a man dying from carcinoma of the stomach with liver secondaries. It is suggested that the serum factor is of a protein (probably globulin) nature, and may have been produced by the diseased liver.     

Quantitation of human serum polymeric IgA, IgA1 and IgA2 immunoglobulin by enzyme immunoassay

This report concerns the relative quantitation of serum polymeric IgA and polymeric IgA subclass concentrations by enzyme immunoassay (EIA). The assay relies on the specific binding of polymeric IgA to secretory component. Competition between pentameric IgM and polymeric IgA for binding to secretory component was observed. Thus, samples were adsorbed for IgM by affinity chromatography before the EIA was performed. The assay was used to determine an age-related range of serum polymeric IgA concentrations and to compare the polymeric IgA concentrations in patients with IgA nephropathy (n = 50) to those of controls (n = 50). The serum concentrations of both polymeric IgA and polymeric IgA1 increased with age reaching adult values of around 12 years of age. Polymeric IgA2 concentrations did not reach adult levels until 18 years of age. The ratio of the polymeric IgA concentration to the total serum IgA concentration was found to be significantly increased in children under 2 years of age compared with those over 4 years of age (Mann-Whitney U-test, P less than 0.01). Patients with IgA nephropathy had significantly increased concentrations of polymeric IgA (P = 0.001) and polymeric IgA1 (P = 0.001) but similar polymeric IgA2 concentrations to controls.     

Peripheral neuropathy in the Twitcher mutant. A new experimental model of endoneurial edema

The Twitcher mouse (Twi/Twi) is a recently identified mutant experimental model for human globoid leukodystrophy. Affected mice develop neurologic abnormalities with demyelination of white matter and peripheral nerve due to an inherited enzyme deficiency. The neuropathy has unusual pathologic features:severe interstitial edema and infiltration by eosinophils. To investigate its pathogenesis and to identify the mechanism of demyelination, we studied vascular permeability and measured endoneurial fluid pressure. Significantly increased endoneurial fluid pressure was detected in clinically affected animals (average, 6.4 cm H2O) versus controls (1.7 cm H2O), and these data are the first measurements of EFP to be reported in mice. Increased vascular permeability to horseradish peroxidase was visualized by electron microscopy with leakage of horseradish peroxidase between endothelial cells and flooding of the endoneurial interstitium. Numerous eosinophils were present in the interstitium, as well as some polymorphonuclear cells, occasional erythrocytes, and degranulating mast cells. Abnormalities of nerve fibers included swelling of Schwann cells with intracytoplasmic inclusions, demyelination, and remyelination. As well as being a model for globoid leukodystrophy, the Twitcher is the first spontaneously occurring experimental model for endoneurial edema and increased endoneurial fluid pressure.     

Peripheral blood mononuclear cell proliferative responses to soluble and particulate heat shock protein 65 in health and inflammatory bowel disease

Objectives: The aims of this study were to determine, in peripheral blood mononuclear cells (PBMC), whether particulate antigen triggers (i) an amplified cell proliferative response compared to soluble antigen and (ii) a dysfunctional response in cells derived from patients with chronic inflammation and specifically in those with inflammatory bowel disease (IBD). Subjects: Healthy volunteers (n = 17), inflammatory controls (n = 8) and patients with IBD (n = 17) were recruited from St Thomas’ and Guys’ Hospital, London, UK. Methods: Following optimisation of experimental conditions (0.1–10.0 μg/ml antigen), PBMC were stimulated with (i) 10.0 μg/ml recombinant soluble heat shock protein 65 (hsp 65) and (ii) 1.0 and 10.0 μg/ml hsp 65 conjugated to microparticles (0.5 μm diameter). PBMC proliferative responses were measured by ³H-Thymidine incorporation at day 5 and results compared between groups using unpaired t-test. Results: Conjugation to microparticles of low dose hsp 65 significantly increased overall proliferative responses by 2–11 fold compared to soluble antigen alone (p < 0.05). However, no specific PBMC proliferative dysregulation was noted in cells from subjects with IBD. Conclusions: Low dose antigen, in microparticulate form, leads to amplified cell proliferation in primary human cells, as showed previously in cell lines and animal studies. However there is no abnormal proliferative response in cells from subjects with IBD. Received 8 February 2006; returned for revision 7 March 2006; accepted by G. Wallace 25 October 2006     

Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity

A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD) locus of the X chromosome has duplicated to specific locations near the pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11. Comparative sequence analysis reveals 92-96% nucleotide identity, indicating that the autosomal ALD paralogs arose relatively recently during the course of higher primate evolution (5-10 million years ago). Analysis of sequences flanking the duplication region identifies the presence of an unusual GCTTTTTGC repeat which may be a sequence-specific integration site for the process of pericentromeric- directed transposition. The breakpoint sequence and phylogenetic analysis predict a two-step transposition model, in which a duplication from Xq28 to pericentromeric 2p11 occurred once, followed by a rapid distribution of a larger duplicon cassette among the pericentromeric regions. In addition to facilitating more effective mutation detection among ALD patients, these findings provide further insight into the molecular basis underlying a pericentromeric-directed mechanism for non- homologous interchromosomal exchange.      

A `house doctor' scheme for primary health care for the single homeless in Edinburgh

The single homeless are a heterogeneous population with health care needs greater than those of the general population. The Edinburgh primary health care scheme for single homeless hostel dwellers is an attempt to provide an easily accessible service for this population. Having continued for eight years it is one of the longest established of such schemes. The original aim was for house doctors to take services to the residents in the hostels but the scheme has developed to include a primary health care team operating from a central clinic.

The scheme was evaluated by a study of the use of the service and by interviews with recipients of the service, hostel managers and others. The study confirmed the high health care burden from chronic handicapping conditions for this population. It was also found that the nature and level of primary health care provided by the scheme was acceptable to the hostel residents and the majority of hostel managements and to accident and emergency department staff. The female hostel dwellers expressed a need for a female practitioner in the scheme. Alternatives for primary health care provision for the single homeless are discussed in the light of the findings, and recommendations are made for the future of the scheme.