PubMed Health⌕ Search

Biomedical subjects

N Holmes

Publications and source records attributed to N Holmes.

9 recordsLinked to original sources
PubMed1991

The pattern of care in families of adults with a mental handicap: a comparison between families of autistic adults and Down syndrome adults.

The pattern of care in 39 families with a mentally handicapped adult member, 20 with Down syndrome, 19 with autism, was studied. There were no significant differences between the mothers, the fathers, or the siblings of Down syndrome and autistic adults in the amount of help offered with physical care, domestic tasks, and supervision duties. However, the brunt of caring fell upon the mothers, with fathers helping mainly with supervision rather than physical care or domestic tasks. Siblings offered less help than fathers. The autistic subjects exhibited significantly more behavior problems. Methods of coping with problems differed: Parents of autistic adults were more likely to "give in" and less likely to tell the handicapped person to stop than parents of Down syndrome adults.

Activities of Daily Living↗
PubMed1990

The human class I MHC gene HLA-F is expressed in lymphocytes.

Genomic and cDNA clones encoding a human, non-classical class I gene, Dew3, have been isolated. The complete coding sequence has been determined. The sequence is capable of directing expression of a protein with high sequence homology to HLA-A,B,C molecules but with a shortened cytoplasmic tail. Sequence comparisons demonstrate that this gene is from a separate locus to the 'classical' HLA-A,B,C and 'non-classical' HLA-E and HLA-G loci. Dew3 is equally distantly related to all of these previously described, functional class I genes. It is, however, extremely homologous to a third 'non-classical' gene, HLA-5.4, and to the chimpanzee gene, Ch28. The RNA species it transcribes is shorter than that of the classical genes, due to an altered acceptor splice site which results in the loss of exon 7. The transcription of Dew3 RNA shows a unique pattern of tissue distribution, being expressed in B cell lines and peripheral blood lymphocytes and absent from T cell lines, fibroblasts and a myelomonocytic leukaemia. A Dew3 protein product was detected after transfection into a human EBV-transformed B cell line but was located intracellularly. The HLA-5.4 gene has been recently designated HLA-F. The Dew3 and X5.1 clones thus represent two new alleles of the HLA-F locus in man. Sequence comparison with its chimpanzee homologue suggests that selective pressure for conservation of amino acid sequence is still maintained at this locus.

Amino Acid Sequence↗
PubMed1989

Expression and function of HLA-A2.1 in transgenic mice.

We have derived a number of transgenic mouse lines which express the human major histocompatibility complex class I gene HLA-A2.1. Two lines carry the complete human HLA-A2.1, the others bear a recombinant gene in which the HLA-A2.1 coding regions are fused to the H-2Kb promoter. Analysis of transgenic spleen cells by immunofluorescence demonstrates that these mouse cells express HLA-A2.1 on their surface in association with mouse beta 2-microglobulin (beta 2m), confirming that HLA-A2 does not require human beta 2m to be expressed at the cell surface. The cells contain more HLA mRNA than endogenous H-2 class I mRNA. There is also a large pool of non-beta 2m-associated HLA heavy chain inside the cell. In contrast the amount of HLA:beta 2m complex is low. Thus, in transgenic mice HLA-A2 seems to compete poorly with H-2 heavy chains for mouse beta 2m. The HLA-A2.1 transgenic mice do not produce influenza-virus-specific cytotoxic T cells (CTL) restricted to the HLA transgene, at least in sufficient numbers to be measured in a direct bulk CTL assay. The dominance of H-2-restricted clones may be the result of quantitative rather than qualitative factors. However, HLA-A2.1 transgenic spleen cells are effective in stimulating an allogeneic CTL response in normal mice. This response is not H-2 restricted. Cold target inhibition studies show that there are at least two populations of CTL, one of which is specific for HLA-A2.1 on mouse cells. This result suggests that at least some allo-CTL are directed against major histocompatibility complex plus "self-peptide".

Animals↗
PubMed1988

Nature of polymorphism in HLA-A, -B, and -C molecules.

Diversity in 39 HLA-A, -B, and -C molecules is derived from 20 amino acid positions of high variability and 71 positions of low variability. Variation in the structurally homologous alpha 1 and alpha 2 domains is distinct and may correlate with partial segregation of peptide and T-cell receptor binding functions. Comparison of 15 HLA-A with 20 HLA-B molecules reveals considerable locus-specific character, due primarily to differences at polymorphic residues. The results indicate that genetic exchange between alleles of the same locus has been a more important mechanism in the generation of HLA-A, -B, and -C diversity than genetic exchange events between alleles of different loci.

Amino Acid Sequence↗
PubMed1986

The primary structure of HLA-A32 suggests a region involved in formation of the Bw4/Bw6 epitopes.

All HLA-B locus molecules have either the Bw4 or Bw6 epitopes. In addition, the Bw4 epitope is found on HLA-Aw23, Aw24, and A32, and Bw6 is also found on HLA-Cw3. The structural basis for these determinants and the evolution of their distribution among products of the HLA-B locus has been a long standing puzzle. To identify residues that may be involved in these determinants, we have cloned a gene for A32 and sequenced the protein encoding exons. Comparison of the predicted protein sequence with other HLA-A,B,C sequences identified residues 79 through 83 of the alpha 1 domain as having a pattern of polymorphic substitution that correlates with the presence and absence of the Bw4 and Bw6 epitopes.

Amino Acid Sequence↗
PubMed1985

Determinants recognized by human cytotoxic T cells on a natural hybrid class I HLA molecule.

The major histocompatibility complex class I HLA molecules are the primary determinants recognized by allogeneic cytotoxic T lymphocytes (CTL), and serve as restricting elements for CTL recognition of viral, chemical, or minor histocompatibility antigens. HLA-Aw69 is a naturally occurring hybrid class I molecule that we have used to investigate the regions of class I antigens involved in human CTL recognition. HLA-Aw69 appears to have resulted from an exon shuffle between two closely related class I genes: the alpha 1 domain of HLA-Aw69 is identical to that of HLA-Aw68, while the alpha 2 and alpha 3 domains are identical to HLA-A2. The determinants recognized by human allogeneic CTL clones specific for HLA-A2, -Aw68, and/or -Aw69 fall into three patterns: (a) CTL determinants are located on both the alpha 1 and alpha 2 domains; (b) interaction of the alpha 1 and alpha 2 domains results in new combinatorial determinants; (c) interaction of the alpha 1 and alpha 2 domains in the hybrid molecule results in the loss of CTL determinants that are present on both parental molecules. Thus, using human CTL clones, target cells, and HLA molecules, we show that the interaction of the alpha 1 and alpha 2 domains alters CTL determinants in ways not directly predictable from primary structure.

Amino Acid Sequence↗
PubMed1979

Propagation of human hepatitis A virus in a hepatoma cell line.

Hepatitis A virus (HAV) was isolated directly from human feces and propagated serially in an HBsAg producing human hepatoma cell line. No cytopathic effect was observed in the tissue culture and no detectable amounts of HAV were present in the tissue culture supernatant fluid. However, increasing amounts of hepatitis A antigen (HAAg) were detected by radioimmunoassay in the cell extracts obtained by freezing and thawing of cells. Specificity of the HAAg determination was shown by neutralization with convalescent sera of marmosets experimentally infected with the MS-1 strain of hepatitis A and by the absence of this neutralization with preinoculation sera. HAAg was first detected after four weeks in the cell extract of infected cultures after inoculation of 10(2)--10(4) tissue culture infectious doses of HAV from second passage.

Antigens, Viral↗