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Biomedical subjects

C M Hill

Publications and source records attributed to C M Hill.

At least 19 recordsLinked to original sources
PubMed1992

Presentation of antigen by mixed isotype class II molecules in normal H-2d mice.

A panel of DBA/2 T cell hybridomas specific for the sperm whale myoglobin epitope 110-121 was found to recognize antigen presented by the mixed isotype class II molecule E alpha dA beta d. The response was blocked by monoclonal antibodies specific for E alpha and A beta d chains; in addition, the hybridomas responded to antigen presented by L cells expressing E alpha A beta d molecules, and made no response with L cells expressing I-Ad or I-Ed molecules. Two more groups of hybridomas isolated from DBA/2 and B10.D2 mice immunized with myoglobin also recognized peptide 110-121 presented by E alpha d A beta d. Thus, although it is expressed at biochemically undetectable levels on spleen cells, the E alpha d A beta d molecule is an important presenting element in normal H-2d mice making a conventional immune response to a protein antigen. These results suggest that high levels of class II expression are not a prerequisite for T cell activation.

Animals↗
PubMed1992

Glomerulonephritis associated with antibodies to neutrophil cytoplasm and glomerular basement membrane.

The prognosis for recovery of renal function of oligoanuric patients with anti-glomerular basement membrane disease is generally regarded as poor. Five patients are reported with dialysis-dependent renal failure in whom antibodies were present simultaneously both to neutrophil cytoplasm and glomerular basement membrane all of whom responded, at least initially, to immunosuppressive therapy and plasma exchange. Two of the 5 remain in clinical and immunological remission at 25 and 51 months of follow-up. We suggest that reversal of dialysis-dependent renal failure may be possible in some patients who display this dual antibody positivity.

Adult↗
PubMed1992

Computer-aided diagnosis.

The author advocates the use of computers to increase the accuracy of diagnosis. Their ability to rapidly sift through large amounts of information and calculate probabilities quickly could provide a useful adjunct to human skills.

Diagnosis, Computer-Assisted↗
PubMed1992

Effect of time of day on aerobic and anaerobic responses to high-intensity exercise.

This study evaluated the effect of time of day on performance of high-intensity, constant-power cycle ergometry by both men and women. Subjects performed all-out cycle ergometer tests in the morning and in the afternoon in randomized order. For all tests, work rate was a constant 5.0 W.kg-1 (women, n = 6) or 6.0 W.kg-1 (men, n = 8). Total work performed was 9.6% greater in the afternoon (mean +/- SE, 348.8 +/- 40.6 J.kg-1) compared to the morning (318.2 +/- 39.5 J.kg-1). The greater amount of work in the afternoon was associated with a 5.1% higher aerobic power and a 5.6% larger anaerobic contribution. There was no interaction between gender and the effect of time of day on the aerobic or anaerobic contributions. These results provide evidence of a circadian rhythm in aerobic and anaerobic responses to high-intensity short-duration exercise, in women as well as in men.

Acceleration↗
PubMed1991

Effect of natural polymorphism at residue 86 of the HLA-DR beta chain on peptide binding.

Class I and class II MHC glycoproteins are highly polymorphic molecules that bind antigenic peptides and present them on cell surfaces for recognition by T lymphocytes. Even though MHC polymorphism has long been known to affect both peptide binding and recognition by the TCR, the role of individual amino acids of MHC proteins in these interactions is poorly understood. To examine the effect of a small number of amino acid residues on T cell stimulation, B lymphoblastoid cell lines homozygous for the closely related DR1 subtypes, Dw1 and Dw20, and the DR4 subtypes, Dw4 and Dw14, were compared for their ability to present an immunogenic influenza hemagglutinin peptide (HA307-319) to an Ag-specific, DR1,4-restricted T cell clone. B cell lines expressing DR1 Dw20 and DR4 Dw14 presented HA307-319 much less efficiently than DR1 Dw1 and DR4 Dw4 and bound a biotinylated analogue of the same peptide less well. Analysis of DRB1 gene sequences suggested that polymorphism at residue 86 had a major effect on peptide binding. Differences in binding of a set of HA307-319 analogues biotinylated at each residue to cells expressing DR1 Dw1 and DR1 Dw20 suggested that the polymorphism affected the interactions of many peptide residues with the class II molecule. In inhibition assays, DR1 Dw1 and DR4 Dw4 were shown to differ from DR1 Dw20 and DR4 Dw14 in their length requirements for peptide binding. Using a larger panel of homozygous B cell lines expressing many class II haplotypes, a Ser-309 substituted HA307-319 analogue was shown to bind to most B cell lines expressing Val-86 containing alleles (including DR1 Dw20 and DR4 Dw14) but failed to bind most B cell lines expressing Gly-86 alleles (including DR1 Dw1 and DR4 Dw4). The results indicated that polymorphism at residue 86 influenced the specificity and affinity of peptide binding and affected the conformation of peptide-DR protein complexes without completely eliminating T cell recognition.

Alleles↗
PubMed1991

Conformational and structural characteristics of peptides binding to HLA-DR molecules.

A fundamental characteristic of MHC class I and class II proteins is their unusual capacity to form stable complexes with a wide spectrum of peptide ligands. In this study, sets of peptide analogues containing long chain-biotinylated lysine individually substituted for each amino acid in the sequence have been used to explore the structural requirements for the formation of peptide-MHC class II protein complexes. Based on the ability of the analogs to bind both the MHC protein and fluorescent streptavidin, receptor contact residues were identified and from their spacing the conformation of the bound peptides could be inferred. Six separate peptides were studied; three defined by HLA-DR1Dw1-restricted T cells, and three identified by T cells restricted through alleles other than HLA-DR1Dw1. The similar patterns of fluorescent signals observed when the former three peptides were studied indicated that they shared conformational features when bound to HLA-DR1Dw1. In contrast when the latter three peptides were examined, the data indicated that they shared some but not all of the conformational features characteristic of the peptides known to elicit HLA-DR1Dw1-restricted T cells. When the peptide sequences were aligned based on the critical contact residues, two positions of structural homology were apparent. In each sequence, an amino acid with a bulky hydrophobic side chain could be identified separated by four residues from a small amino acid. These minimal structural requirements were consistent with recent experiments demonstrating that only a small number of side chains in the peptide were necessary for binding to the MHC protein.

Amino Acid Sequence↗
PubMed1991

Histological changes following submucosal Teflon injection in the bladder.

Histological examination following subureteric Teflon injection was carried out on 32 ureters and four granulomatous polyps. When the Teflon was correctly placed in the submucosa it remained circumscribed and reflux was more likely to be corrected. If the Teflon was placed more deeply it became diffuse, caused a giant cell reaction, and was less likely to correct the reflux. The granulomatous polyps may represent a reaction to leakage of Teflon from the injection site.

Foreign-Body Reaction↗
PubMed1990

Genetic toxicology of tricyclic carboxamides, a new class of DNA binding antitumour agent.

(N-[2-(Dimethylamino)ethyl]acridine-4-carboxamide (acridine carboxamide; NSC 601316) is an acridine-derived experimental antitumour agent with curative properties against Lewis lung carcinoma in mice. Although it intercalates into DNA and also appears to interact with topoisomerase II, its DNA binding properties appear distinct from other acridine derivatives such as the clinical antitumour drug, amsacrine. The mutagenic properties of acridine carboxamide, together with three related compounds containing either 9-aminoacridine or phenazine chromophores, were studied at the 6-thioguanine and ouabain loci in cultured V79 Chinese hamster fibroblasts. Each compound, when tested at concentrations causing up to 90% kill, had weak but significant activity at the 6-thioguanine but not at the ouabain locus. All drugs were potent inducers of micronuclei, indicating high clastogenic activity. There was a highly significant relationship between mutation frequency (as resistance to 6-thioguanine) and either cytotoxicity (measured as D37 in a clastogenicity assay) or clastogenicity. A broader range of compounds was also tested for microbial mutagenicity. In Salmonella typhimurium strains, none were mutagenic in TA98, TA100 or TA102 but several were mutagenic in TA1537, a frameshift tester strain. Some drugs also caused 'petite' mutagenesis in Saccharomyces cerevisiae. In general, compounds with the phenazine chromophore, which has no positive charge, were the most mutagenic in these systems. However, activity was not related to mammalian mutagenicity or antitumour effect. The results suggest that in mammalian cells, the cytotoxicity, clastogenicity and mutagenic activity of these drugs are mediated by similar mechanisms to those for amsacrine analogues, probably involving the enzyme DNA topoisomerase II.

Acridines↗
PubMed1990

Definition of murine T helper cell determinants in the major capsid protein of human papillomavirus type 16.

Three murine major histocompatibility complex (MHC) class II-restricted T cell determinants were identified in the major capsid protein L1 of human papillomavirus (HPV) type 16. Peptides derived from HPV-16 L1, which contain putative T cell epitopes located by a predictive algorithm, were synthesized and tested for lymphoproliferative activity by direct immunization, followed by in vitro assay of responses to peptides or recombinant HPV-16 L1. The MHC restriction of the stimulatory peptides was determined using blocking monoclonal antibodies against class II molecules. The responses, which were specific for the priming peptides alone, cross-reacted with recombinant L1 but not with analogous peptides derived from other HPV types.

Amino Acid Sequence↗
PubMed1990

Heart transplantation--an autopsy review.

Cardiac transplantation is now a well recognised form of treatment for several forms of end stage cardiac failure, particularly ischaemic heart disease and cardiomyopathies. By the end of 1988, seven patients from Northern Ireland had received cardiac transplants in Papworth and Harefield Hospitals. Of these, four have died, three as a result of rejection and the fourth from widespread cytomegalovirus infection. The autopsy findings in these four cases are presented in this paper.

Adult↗
PubMed1989

Spontaneous regression of congenital epulis of the newborn.

An infant with congenital gingival epulis which spontaneously regressed over the first year of life is reported. A policy of conservative management should be adopted in this condition unless there are feeding problems in the newborn period or reasons to doubt the diagnosis.

Female↗
PubMed1989

Ten-year results of renal transplantation using only azathioprine and low-dose prednisolone as immunosuppression.

This paper describes the results of renal transplants carried out in a single center more than 10 years ago. One hundred fifty-five recipients received 170 grafts; 164 from cadavers and 6 from living-related donors. All patients received the same immunosuppressive therapy with azathioprine and low-dose steroid. 1. The total actual patient survival was 67.1% at 10 years; 104 patients survived and 51 died. 2. The actual first cadaver graft survival was 54.7% at 10 years; 82 grafts survived and 68 were lost. Death with a functioning graft was the commonest cause of graft loss. 3. Ninety-seven patients and 70 first cadaver grafts survived in the 12th year. Two patients survived with first cadaver grafts into the 21st year. 4. Tissue match grade was not related to cadaver graft survival at 10 years. 5. Five of the 6 recipients of living-related donor kidneys survived but only 3 of their grafts were functioning after 10 years.

Adolescent↗