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N Hughes-Jones

Publications and source records attributed to N Hughes-Jones.

8 recordsLinked to original sources
PubMed1996

A structural model for 30 Rh D epitopes based on serological and DNA sequence data from partial D phenotypes.

Both cDNA RHD sequences and reactivity with monoclonal anti-D have been reported in a number of partial D phenotypes, where parts (some epitopes) of the normal D antigen are missing, and anti-D of restricted specificity may be made in response to challenge with normal D positive blood. This paper analyses these reports together and proposes a model for the structure which comprise the epitopes of the Rh D antigen. Some epitopes are proposed to be comprised of continuous peptide sequence within one extracellular loop, whereas others require interactions between two or the extracellular peptide loops.

DNA↗
PubMed1992

Clonally related IgM rheumatoid factors undergo affinity maturation in the rheumatoid synovial tissue.

Using hybridoma technology we established a panel of human monoclonal rheumatoid factors (RF) from the synovial tissues of two patients with rheumatoid arthritis (RA), and one patient with polyarticular juvenile RA. Nucleotide sequence analysis of the V regions of these RF indicates that two independently derived antibodies from one of the RA patients are clonally related. One of these antibodies appears to be close to germ-line configuration, whereas the other has accumulated a total of 36 substitutions in both H and L chains. Measurements of the affinity for human IgG of the two RF show that the extensively mutated RF has 100-fold higher affinity for IgG than the RF close to germline. These findings indicate that IgM RF in RA can undergo affinity maturation and suggest that certain RF may be the product of an Ag-driven immune response.

Amino Acid Sequence↗
PubMed1987

Synergistic complement lysis by monoclonal antibodies to the human leukocyte common antigen requires both the classical and alternative pathways.

In a previous study we isolated a series of rat monoclonal antibodies to the human leukocyte common (LC) antigen and demonstrated that synergistic complement lysis was possible between IgG2b antibodies which recognised different epitopes. In this report we have examined the mechanisms that were involved in synergistic lysis. We found that the number of C1q binding sites increased from 30,000 to 40,000/cell using a single antibody to 90,000/cell when two IgG2b antibodies to different epitopes were used together. The affinity of C1q binding also increased approx. 3-fold for the synergistic pair, and there was a similar increase in the rate of C1 activation. Combinations of an IgG2b with IgG1 or IgG2a gave much smaller increases in the amount of C1q bound and in the rate of C1 activation. Despite the large number of C1q molecules bound with the optimal synergistic pair and the increased rate of C1 activation, lysis was inefficient in serum depleted of Factor D, suggesting a requirement for the alternative pathway. This is the first demonstration of the need for the alternative pathway in complement lysis by monoclonal antibodies.

Animals↗
PubMed1986

The efficient production of stable, human monoclonal antibody-secreting hybridomas from EBV-transformed lymphocytes using the mouse myeloma X63-Ag8.653 as a fusion partner.

The mouse myeloma X63-Ag8.653 was fused to peripheral blood lymphocytes (PBL) from apparently healthy individuals, autoimmune patients and volunteers immunised with Rhesus (D) positive erythrocytes. Fusions were performed with or without prior transformation of PBL with Epstein-Barr virus (EBV). Using untransformed PBL, under the best conditions a mean fusion frequency of 8.4 X 10(-6) was obtained, with 22% of the resulting hybridomas secreting human immunoglobulin. Fusions with EBV-transformed cells gave fusion frequencies of 1.0 X 10(-4), with 85-90% of hybridomas secreting human immunoglobulin. The heterohybridomas formed in both cases cloned efficiently and had doubling times of 24-30 h. The heterohybridomas secreted human IgM, IgG and IgA of both kappa and lambda isotypes and culture supernatants contained up to 50 micrograms ml-1 of human immunoglobulin. Mouse immunoglobulin was not detected in the culture supernatants. 28 hybrids were selected for vigorous growth and antibody production by repeated cloning. Immunoglobulin synthesis was stabilised in 26 of these hybridomas after two or three cloning steps. The heterohybridomas have been successfully grown in large volumes for periods up to 15 months. It is concluded that the mouse myeloma X63-Ag8.653 is a suitable fusion partner with EBV-transformed B cells in the efficient production of human monoclonal antibodies.

Animals↗
PubMedDate not supplied

Inter-group aggression: the multi-individual organism and the survival instinct.

Inter-group aggression, carried out at the level of the in-groups and out-groups of ethnocentric theory, continued unabated throughout the twentieth century. Its frequency, together with its ferocity, indicates a potent biological cause. We have evolved as social animals, and it is postulated that evolution has proceeded to such an extent that 'multi-individual social organisms', that is, 'social groups that fight each other are self-sustaining, self-replicating whole containing interdependent parts'. This results from the total integration of individuals into the social structure and culture of the in-group; individuals are inseparable from their society and evidence for this proposal is given. Cohesion is given through the collective consciousness and collective memory. The analogy is to multicellular organisms that evolved from the association of single cell organisms. All biological organisms are subject to the survival instinct, which is thus the potent biological cause of inter-group aggression. Groups compete for territory and see other groups as a threat. Prevention of inter-group aggression should come from the insight that threatening behaviour endangers the integrity of the society of out-groups, initiating conflict.

Aggression↗