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B Knight

Publications and source records attributed to B Knight.

At least 19 recordsLinked to original sources

Induction of adjuvant arthritis in mice.

Adjuvant arthritis, induced by injections of Freund's complete adjuvant into the footpads of some rat strains, has been recognized as a useful animal model for many years. There has, however, been notable lack of success in reproducing this model in other species. We now describe the development of adjuvant arthritis in healthy strain mice approximately 2 months after injection of Freund's complete adjuvant. Although the clinical appearance of the mice and the joint histopathology closely resemble the adjuvant arthritis reported in the rat, we were unable to detect rheumatoid factor in sera from the affected animals. In parallel studies of T cell proliferation, affected animals responded to some mycobacterial antigens but not to the 65-kD heat shock protein of Mycobacterium tuberculosis, suggesting that some other epitope is important in the development of the disease.

Animals

Analysis of antibody reactivity in the sera of 42 patients with paraproteinaemia.

The clinical expression of disease in patients with conditions in which autoimmunity is thought to contribute to the pathogenesis of disease is the result of an unfortunate combination of predisposing and environmental factors. The presence of autoantibodies showing a variety of antigen specificities in sera from many of these patients has been closely correlated with particular spectra of organ involvement or tissue destruction. Their precise role in the disease process is as yet unclear. Sera from patients with paraproteinaemia also often contain autoantibodies to a variety of cell components, although symptoms of autoimmune disease are rarely found in this group of individuals. In this study of 42 sera from patients with paraproteinaemia we have confirmed the presence of autoantibodies in 33% (13/42) of samples. Amongst the autoantibodies detected were those to human neutrophils (3), U1RNP (8) and cardiolipin (4). In five sera, the immunoglobulin class of autoantibody did not correlate with that of the monoclonal band. This study extends previous reports of the repertoire of autoantibodies present in sera from patients with paraproteinaemia.

Antibodies, Anticardiolipin

Independent analysis of the 16/6 idiotype lupus model. A role for an environmental factor?

The recent description of a lupus-like disease in normal mice after injections of human mAb that bind DNA and carry the common Id 16/6 Id has excited much attention. In an effort to reproduce this model we have performed two experiments using eight human mAb three of which bear the 16/6 Id. Despite using an injection protocol very similar to that of the original authors and waiting for up to 1 yr we were unable to detect any autoantibodies or any evidence of renal disease. We suspect that our failure to reproduce the model may be due to differences in either or both the batches of CFA used, or in the animal house environments. It supports the view that a mosaic of effects is required to induce clinical expression of an autoimmune disease.

Animals

Identification of the 664 proline to leucine mutation in the low density lipoprotein receptor in four unrelated patients with familial hypercholesterolaemia in the UK.

Mutations in the gene for the low density lipoprotein (LDL) receptor cause Familial Hypercholesterolaemia (FH). One such mutation, a cytosine to thymine change in the codon for amino acid 664, causes proline (CCG) to be replaced by leucine (CTG) at this position, and creates a Pst I site in exon 14 of the gene. This mutation, previously identified in an FH homozygote of Asian Indian origin, results in a receptor with a reduced binding affinity for LDL and in delayed processing of the precursor form of the protein in cultured cells. A total of 224 unrelated heterozygous and 4 homozygous FH patients from London was screened for this mutation using direct amplification of genomic DNA by the polymerase chain reaction (PCR) and restriction digestion of the PCR product. Four patients were identified who were heterozgous for this mutation and the C to T base change was confirmed by sequencing. Affected relatives of these patients were also found to have the mutation. The effect of the mutation on LDL-receptor function in lymphoblastoid cell lines obtained from two of these patients was similar to that observed in heterozygous relatives of the original proband (MM). Eight polymorphisms of the LDL receptor gene were used to determine the haplotype of the defective allele carried by the patients and the individual (MM) in whom the mutation was first discovered. Two different haplotypes were found, suggesting that the mutation, which occurs at a CpG 'hotspot', has arisen independently at least twice. The presence of the same single base change in the LDL-receptor gene in several unrelated patients has not previously been reported in a population which is not geographically or culturally isolated.

Adolescent

Homicide by rectal insertion of a walking stick.

A 75-year-old disabled man was killed by a homosexual mental patient by the rectal insertion of a walking stick. The external examination of the body showed only four superficial tears in the skin of the anus. However, there was a 1 cm diameter full thickness perforation in the anterior wall of the rectum and the cause of death was the perforated rectum. The importance of the careful investigation into the circumstances of death, the background of the decreased, and the condition of the anus and rectum is discussed.

Aged

The Medieval Coroner.

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Coroners and Medical Examiners

Evaluation of eosin-fluorescence in the diagnosis of sudden cardiac death.

The diagnostic significance of the eosin-fluorescence method was evaluated and compared with the enzymehistochemical beta-hydroxybutyrate-dehydrogenase method (beta-HBDH) and the degree of hyperchromasia in 568 samples from 24 bets-HBDH-negative and beta-HBDH-positive sudden cardiac deaths (SCD) and 23 non-cardiac deaths as controls. The effect of autolysis was investigated separately on isolated human hearts at +4 degrees C and +22 degrees C. All samples were examined without any knowledge of clinical or autopsy data. Normal olive-green fluorescence was observed in only five individuals of the control group and two in the beta-HBDH-negative one. The frequency of the yellow-fluorescence and hyperchromasia increased from the control subjects towards the beta-HBDH-positive-ones. The difference in frequency distribution of fluorescence between the groups was statistically highly significant (P less than 0.001). The change in fluorescence did not correlate with the loss of beta-HBDH-reaction or the distribution pattern of hyperchromasia. Postmortem autolysis did not change the fluorescence significantly but the 78% wrong positive subjects in the control group render this method too sensitive and unreliable for medicolegal purposes.

Adult