Search PubMed⌕ Search

Biomedical subjects

N Holmes

Publications and source records attributed to N Holmes.

48 records · Page 3Linked to original sources
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↗
PubMed1985

Exon shuffling in vivo can generate novel HLA class I molecules.

The human class I histocompatibility molecule HLA-Aw69 has serological and structural properties which suggested it was a hybrid of the allelic products HLA-A2 and HLA-Aw68. We have now isolated three genes for HLA-Aw69 and one gene for HLA-Aw68. The sequences of exons encoding the entire extracellular portion of the molecule and of intron 2 have been determined. Their comparison with the published sequence of HLA-A2 proves that HLA-Aw69 is a hybrid molecule with complete identity to HLA-Aw68 in the alpha 1 domain and with HLA-A2 in the alpha 2 and alpha 3 domains. This comparison also localised regions involved in the epitopes recognised by monoclonal antibodies. The three HLA-Aw69 genes obtained from unrelated individuals of diverse ethnic backgrounds are identical. All results are consistent with HLA-Aw69 having arisen by a single reciprocal recombination event between the HLA-Aw68 and HLA-A2 genes somewhere in a region of 86 bp about the 3' donor splice site of exon 2. Estimates of the silent mutation rate in HLA genes suggest this event occurred not more than 330 000 years ago. Intra-allelic reciprocal recombination thus represents a further mechanism in addition to gene conversion for the generation of novel class I histocompatibility alleles.

Alleles↗
PubMed1985

The use of the Leiter International Performance Scale with autistic children.

This paper discusses the advantages and disadvantages of using the Leiter International Performance Scale with autistic children and presents the results of a study comparing the performance of 18 autistic children on the Wechsler Intelligence Scale for Children-Revised and the Leiter. The results showed a high positive correlation between the WISC-R full scale IQ, the WISC-R performance IQ, and the Leiter IQ. There was no significant difference between the mean Leiter IQ and the mean WISC-R performance scale IQ, but there was a significant difference between the mean Leiter IQ and the mean WISC-R full scale IQ. There was a low correlation between the WISC-R verbal IQ and the Leiter IQ, and the means were significantly different. Reading attainment scores correlated positively with both the WISC-R IQ and the Leiter IQ.

Adolescent↗
PubMed1984

Comparison of the primary structures of clathrin light chains from bovine brain and adrenal gland by peptide mapping.

The structures of the polymorphic forms of clathrin light chains were analyzed by two peptide mapping procedures. Comparison of the products of partial digestion by V8 protease showed no common peptides between LCA and LCB from bovine brain. No similarities between clathrin light chains and tropomyosin chains from bovine brain and skeletal muscle were detected with this technique. The peptides produced by complete tryptic digestion of LCA and LCB from bovine brain and bovine adrenal gland were analyzed by reverse phase h.p.l.c. For both LCA and LCB the polypeptides from different tissues showed considerable homology. LCA from brain and adrenal gland shared 10 out of a total of 15 peptides. LCB from brain and adrenal gland shared 10 out of 14 peptides. In contrast, when LCA was compared with the LCB chain from the same tissue very few peptides were shared; 4/23 for brain and 3/21 for adrenal gland. These results strongly indicate that, within a tissue, LCB is not related to LCA by post-translational processing and that each chain is encoded by a separate gene. The data also demonstrate the close homology of the different forms of LCA and LCB expressed in different tissues within the same organism. Thus the polymorphic differences of clathrin light chains within a tissue are greater than those between tissues.

Adrenal Glands↗
PubMed1984

Molecular characterization of HLA-A28*, a novel HLA product, and its relationship to HLA-A28 and HLA-A2.

The HLA-A28* molecule expressed by the B-cell line IDF is serologically distinct and intermediate between HLA-A28 and HLA-A2. Comparative tryptic peptide mapping of biosynthetically labeled HLA-A28*, A28, and A2 molecules showed that HLA-A28* is also chemically distinct. Reverse-phase high pressure liquid chromatographic analysis of tryptic peptides labeled with 3H-arginine and 3H-lysine revealed that A28*, A28, and A2 share approximately 65% of their tryptic peptides. Multiple differences were observed between A28* and both A28 and A2. No peptides unique to A28* were detected and 25 peptides were shared with both A28 and A2. These results show that A28* is a novel HLA product that is closely related to A28 and A2. Tryptic peptide map comparisons of these molecules labeled separately with 11 amino acids confirm these results. The data suggest that HLA-A28* may have arisen from a genetic exchange event involving HLA-A28 and -A2. These data are consistent with the hypothesis that A28* is identical with A28 in the first extracellular domain (alpha 1) and identical with A2 in the second domain (alpha 2).

Antibodies, Monoclonal↗
PubMed1983

Language development in a group of very low-birth-weight children whose postauricular myogenic response was tested in infancy.

A new instrument for the detection of the postauricular myogenic (PAM) response was used to test the hearing of 106 infants weighing less than or equal to 1,500 g when they were aged 1 to 21 months. Eighty-eight infants showed a positive response at 60 dB hearing level (HL) (normal). The other 18 did not respond; four were found to have sensory neural hearing loss and another six had conductive loss due to secretory otitis media. Of the 106 children, 90 aged 2 years or more (mean 27 months) were living in the United Kingdom, and their language development was assessed. It was normal in 67/75 children whose PAM response had been normal in infancy. The remaining eight children with normal PAM responses in infancy, had language delay. All eight children had problems that were thought to account for the delay, including three with mental retardation, three with cerebral palsy, and two whose families did not speak English. Language development was normal in 11/15 children tested whose PAM responses had been found to be abnormal, including all six whose secretory otitis media had been diagnosed and treated at the time of the PAM test. Delay in language development was found in 3/4 children with sensory neural hearing loss who were available for testing and in one child with overall developmental delay. It is concluded that a positive PAM response at 60 dB HL in infancy indicated hearing adequate for the development of normal speech in otherwise normal children among a group of infants at high risk of hearing loss.

Child, Preschool↗
PubMed1982

Parents as cotherapists: their perceptions of a home-based behavioral treatment for autistic children.

Parents' views about acting as cotherapists in a home-based behavioral treatment for their autistic child were investigated. Three areas were studied: (1) the demands involved in being a cotherapist, (2) whether parents felt more able to cope with their child after treatment, and (3) whether they had the same conception of the treatment's aims as did the therapists involved. Parents viewed their treatment more favorably than a comparison group of parents receiving more usual forms of treatment. Most had an accurate impression of treatment but half found it hard to use the methods suggested. Although parents felt that their child improved as a result of treatment, several had stopped using the techniques or felt unable to apply them to new problems.

Autistic Disorder↗
PubMed1982

Prevalence of autism and related conditions in adults in a mental handicap hospital.

The proportions of subjects with severe social impairment and those retaining the features of childhood autism were investigated in a population of mentally retarded adults in a long-stay hospital. The results confirmed the findings of an earlier study of mentally retarded children (Wing & Gould, 1979) that the administrative category of mental retardation includes a substantial minority of people with severe impairment of two-way social interaction. Such social impairment occurred in 38% of the adult population and was very significantly associated with abnormalities of communication and imaginative activities. Muteness, repetitive stereotyped behaviour, including repetitive speech, and a range of behaviour problems also occurred more frequently in the socially impaired group. Two methods of sub-classifying the socially impaired were compared. Classification based on the severity of social impairment gave more statistically significant associations with behavioural and psychological variables than did a method based on the presence or absence of typical autism. The implications of these findings and their relevance for management and planning of services for the mentally retarded were briefly discussed.

Adolescent↗
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↗
PubMedDate not supplied

Use of an 125I-labelled DNA ligand to probe DNA structure.

It no longer seems likely that DNA molecules in situ have a uniform conformation, represented by the classical B-form helix. For example, recent structural studies have shown that in certain conditions DNA can have a left-handed (so-called Z-form) helix, and have revealed extensive sequence-dependent variations of B-DNA helical parameters. Such sequence-dependent variations in DNA structure can be investigated in solution with reagents that bind to DNA in a conformation-dependent manner, and cut one or both strands of the double-helix at the site of binding, as, for example, has been shown for the endonuclease DNase I3. We describe here a simple way to endow a DNA-binding ligand with the ability to cleave DNA--labelling with 125I. The radiochemical damage associated with 125I decay induces a double-stranded DNA break. Using this technique we have shown that a sequence of four consecutive A X T base pairs is a necessary, but not sufficient, condition for strong binding to DNA of the bis-benzamide Hoechst 33258--presumably the other important factor is the conformation of the double-helix at the site of the (A/T)4 sequence. We suggest 125I-Hoechst 33258 may be a useful new probe of DNA structure.

Base Sequence↗
PubMedDate not supplied

Clathrin light chains contain brain-specific insertion sequences and a region of homology with intermediate filaments.

The primary structures of four bovine clathrin light chains have been determined. Light chains LCa and LCb are homologous proteins encoded by different genes. In the brain the messenger RNA from these genes undergoes differential splicing to yield proteins having centrally inserted brain-specific sequences. A potentially alpha-helical region of the clathrin light chains shows homology with intermediate filament proteins.

Amino Acid Sequence↗