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Biomedical subjects

C R Bangham

Publications and source records attributed to C R Bangham.

At least 73 records · Page 4Linked to original sources
PubMed1991

Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition.

In a longitudinal study of HIV seropositive patients, there were fluctuations in the specificity of cytotoxic T cells for the virus. This was matched by variability in proviral gag DNA epitope sequences in the lymphocytes of these patients. Some of these viral variants are not recognized by autologous T cells. Accumulation of such mutations in T-cell antigenic targets would provide a mechanism for immune escape.

Amino Acid Sequence↗
PubMed1990

Defective interfering particles: effects in modulating virus growth and persistence.

Defective interfering virus particles (DIP) frequently play an important part in viral persistence in vitro, and may in some instances modify a virus infection in vivo, causing attenuation or persistence of the infection. To explain certain aspects of the growth of these mutants in vitro, other factors have been invoked such as interferon, mutations in the wild-type virus or the infected cells, or other substances released by infected cells that attenuate the infection. We present here a simple model of the growth of DIP in vitro which shows that (a) the observed population dynamics of DIP can readily be explained without invoking such extrinsic factors; (b) the initial multiplicity of infection of DIP is the principal determinant of the outcome of infection in both single- and repeated-passage cultures; and (c) in a long-term culture in vitro, the criterion used to decide the time of virus passage directly determines how long the standard virus, DIP, and cells survive. This model may be used with minor modifications to predict the behavior in vitro of other mutant viruses with a dominantly interfering phenotype.

Biological Evolution↗
PubMed1990

Sequence variants of human T-cell lymphotropic virus type I from patients with tropical spastic paraparesis and adult T-cell leukemia do not distinguish neurological from leukemic isolates.

We have amplified and sequenced DNA in the envelope (env) and long terminal repeat (LTR) regions of human T-cell lymphotropic virus type I (HTLV-I) proviruses from the peripheral blood of 10 HTLV-I-seropositive patients with tropical spastic paraparesis (TSP) and two patients with adult T-cell leukemia. The aim was to examine variation in these regions and to test the hypothesis that the sequences of leukemogenic HTLV-I isolates differ from those causing the neurological disease TSP. In 5 of the 12 HTLV-I-seropositive patients, more than one HTLV-I sequence variant was identified in the same individual. No two individuals shared identical sequences in either env or LTR U3. Sequence variations were found at 73 positions in 1,416 bases amplified in env. Sequence variability was found throughout the LTR-U3 region, including the sequences of two transcriptional enhancers. Several nucleotide changes common to both Caribbean and Japanese HTLV-I isolates allowed us to identify a consensus sequence that differs from the HTLV-I prototype sequence (M. Seiki, S. Hattori, Y. Hirayama, and M. Yoshida, Proc. Natl. Acad. Sci. USA 80:3618-3622, 1983). No sequence in the env or LTR U3 region was found to be characteristic of isolates from TSP patients. Although each isolate was distinct at the nucleotide level, the predicted protein sequence of HTLV-I env is less variable than that of human immunodeficiency virus env, suggesting that these lymphotropic retroviruses use different strategies to evade host immune responses.

Adult↗
PubMed1989

Recognition of respiratory syncytial virus fusion protein by mouse cytotoxic T cell clones and a human cytotoxic T cell line.

Two mouse cytotoxic T cell (Tc) clones, D5 and H11a, with specificity for the respiratory syncytial virus (RSV) fusion protein (F) were derived from BALB/c mice primed intranasally (i.n.) with RSV (A2 strain). These clones possessed essentially the same characteristics, and only clone H11a is described here. Tc clone H11a lysed target cells infected with a recombinant vaccinia virus (VV) expressing the RSV F gene, and similar target cells infected with RSV strains Long, 8/60, or 18537. In addition, two RSV-specific mouse Tc lines are described, from BALB/c mice primed i.n. with RSV A2 (Tc line MJC-A2), or intraperitoneally with a VV-RSV F gene recombinant (Tc line MJC-F). Tc line MJC-A2 was of unknown antigen specificity, failing to lyse targets infected with recombinant VVs expressing the RSV nucleoprotein (N), large glycoprotein, F, 1A, 1C, or partial matrix protein (amino acid residues 88 to 257) genes. MJC-A2 Tc were cross-reactive for all strains of RSV tested. In contrast, the F-specific MJC-F Tc showed a marked degree of RSV strain specificity, efficiently lysing targets infected with RSV Long or A2 strains, but showing greatly reduced lysis of targets infected with RSV 8/60 or 18537 strains. An anti-RSV human Tc line, IH.K2, also recognized the fusion protein. IH.K2 Tc efficiently lysed autologous Epstein-Barr virus-transformed B cells (BCL) persistently infected with RSV A2 and BCL infected with a VV-RSV F gene recombinant. IH.K2 function was not exclusively RSV F-specific, however, as these cells also lysed autologous BCL infected with a VV-RSV N gene recombinant. These data show that the RSV fusion protein is a target antigen for anti-RSV Tc following infection of mice and humans, and that the F-specific Tc repertoire in mice can be influenced by the method and route of priming.

Animals↗
PubMed1988

Enzymatic amplification of exogenous and endogenous retroviral sequences from DNA of patients with tropical spastic paraparesis.

Using oligonucleotide primers that hybridize to conserved sequences in the reverse transcriptase (RT) gene, we have amplified by the polymerase chain reaction three sequence variants of HTLV-I from the genomic DNA of five patients with tropical spastic paraparesis (TSP), and a fourth sequence variant from a healthy carrier of HTLV-I. These results unequivocally identify the retrovirus associated with TSP as HTLV-I and suggest that no sequence variant is uniquely responsible for the condition. The same primers served to amplify two novel single-copy endogenous retroviral RT sequences related to the exogenous mammalian leukaemia viruses: and three KpnI (LINE1) family DNA repeats. This strategy, combining the sensitivity of PCR with cross-reactive primers, may be useful in the search for known or novel retroviruses in other diseases of possible retroviral aetiology.

Amino Acid Sequence↗
PubMed1988

An interactive computer program for the analysis of HLA class II restriction fragment patterns.

There is considerable current interest in the application of Southern blotting and hybridization, with locus-specific HLA class II probes, to HLA typing. The work of several laboratories has shown that, under suitable conditions, restriction fragment patterns that correlate with DR and DQ serology and with DP cellular reactivities can be obtained from homozygous cell lines. Although the identification of class II specificities from restriction fragment patterns is relatively straightforward in homozygotes, the increased complexity of the patterns obtained from heterozygotes makes the interpretation considerably more difficult; this difficulty is compounded by even slight variation between and within gels. We have developed an interactive computer program that allows HLA-DR and DQ typing by the visual matching of restriction fragment pattern data with standard data derived from a panel of well-characterized homozygous cell lines. The program also uses a simple algorithm (after Southern) to estimate the fragment sizes in the unknown track. The screen display can be printed out to give a convenient record of the match; a numerical measure is also given of the goodness of fit of the new data.

Algorithms↗
PubMed1986

Human and murine cytotoxic T cells specific to respiratory syncytial virus recognize the viral nucleoprotein (N), but not the major glycoprotein (G), expressed by vaccinia virus recombinants.

The viral antigens recognized by cytotoxic T cells (CTL) have not been defined in most viruses infecting mouse or man. Natural or artificial virus recombinants can be used to determine the antigen specificity of CTL directed against viruses with segmented genomes, such as influenza, but this technique is more difficult to apply to the study of unsegmented viruses. We describe here the use of recombinant vaccinia viruses, containing cDNA corresponding to either the nucleoprotein (N) gene or the major surface glycoprotein (G) gene of human respiratory syncytial virus (RSV), to examine the antigen specificity of anti-RSV cytotoxic T cells from humans and mice. The results demonstrate that the RSV N protein is one of the target antigens for CTL in man and mouse, whereas the G protein was not recognized and can at best represent a minor target antigen for CTL.

Animals↗
PubMed1986

Specific human cytotoxic T cells recognize B-cell lines persistently infected with respiratory syncytial virus.

The T-lymphocyte response to respiratory syncytial (RS) virus has been invoked to explain the bronchiolitis and pneumonia caused by RS virus in human infants. However, T cells also appear to play a role in protection against RS virus infection. Although RS virus-specific human lymphocytes have been demonstrated, neither the phenotype nor the function of the lymphocytes was characterized. We describe here the induction of anti-RS virus cytotoxic T lymphocytes, in both bulk culture and restimulated cell lines, from human peripheral blood. Infection of Epstein-Barr virus-transformed human B-cell lines with RS virus in vitro readily caused a persistent infection; these cells continued to synthesize RS viral proteins and secrete infectious RS virus 4 months after infection. The persistently infected cells were used both to restimulate cytotoxic-T-cell precursors and as targets for RS virus-specific cytotoxic T cells.

Antibodies, Monoclonal↗
PubMed1986

Murine cytotoxic T cells specific to respiratory syncytial virus recognize different antigenic subtypes of the virus.

The aim of this study was to establish whether cytotoxic T cells (Tc), raised against respiratory syncytial virus (RSV) in the mouse, are specific to the strain of immunizing virus, or cross-reactive between virus strains. Several recent studies using monoclonal antibodies have begun to define the antigenic variation among strains of RSV. It is likely that a successful RSV vaccine will need to contain antigenic determinants from more than one subtype, but since only the highest levels of neutralizing antibody are able to give complete protection against RSV infection, a vaccine may also need to elicit a cellular immune response. We have recently described H-2-restricted, RSV-specific Tc following RSV infection in the mouse; we present here evidence that polyclonal RSV-specific Tc in the mouse recognize syngeneic target cells infected with every human strain of RSV tested, whatever the subtype. The only RSV strain that appeared not to be recognized was bovine RSV, which seems unable to infect mouse cells; however, bovine cells, infected with bovine RSV and fixed with glutaraldehyde, primed mice for Tc which recognized human strains of RSV.

Animals↗
PubMed1986

Passively acquired antibodies to respiratory syncytial virus impair the secondary cytotoxic T-cell response in the neonatal mouse.

Passively acquired antibody has been known since the 1940s to impair the secondary antibody response to the homologous antigen. However, the effect of passive immunity on the T-cell response is largely unknown. The results presented here demonstrate that monoclonal antibodies (Mabs) to respiratory syncytial virus (RSV), transferred in the mother's milk or injected directly, can reduce the generation of RSV-specific cytotoxic T-cell (Tc) precursors by the neonatal mouse; the development of influenza-specific Tc was unaffected. Both non-neutralizing and neutralizing antibodies, and Mabs directed against either the fusion (F) or G proteins of RSV, can impair the secondary Tc response. The ability of a given antibody to produce this impairment depends on its titre and its subclass, which determines its absorption from the gut by the neonate. These results are of interest in relation to virus infections in humans, such as RSV or measles, which are often contracted in the first 6 months of life, when maternal antibody is still present in high titre.

Animals↗
PubMed1985

Cytotoxic T-cell response to respiratory syncytial virus in mice.

The role of the humoral and cellular arms of the immune response in protection against respiratory syncytial virus (RSV) infection and in the pathogenesis of the severe forms of this disease is poorly understood. The recent demonstration that some inbred mouse strains can be infected with RSV has opened the way to a detailed investigation of RSV immunity. We report here the finding of major histocompatibility complex-restricted, RSV-specific memory cytotoxic T cells in the spleens of BALB/c and C57BL mice after intranasal infection; these T cells recognize the Long, A2, and 8/60 (human) strains of RSV. Both K and D locus major histocompatibility complex alleles can restrict the cytotoxic response; however, in the two haplotypes tested, Dd is a low-responder allele and Kb is a nonresponder allele for RSV. UV-inactivated RSV (when given intraperitoneally) can prime mice for development of cytotoxic T cell memory, restimulate cytotoxic T cell cultures in vitro, and form a target for the cytotoxic cells.

Animals↗
PubMed1981

The prevalence of immediate positive skin tests in Nepalese children.

Two hundred and ninety-three normal schoolchildren between 5 and 15 years old living in the hills of Eastern Nepal were tested by the skin prick method for sensitivity to six allergens: Dermatophagoides pteronyssinus, Aspergillus fumigatus. Cladosporium herbarum, Penicillium notatum, mixed pollens and mixed threshings. These children were also questioned and examined for symptoms and signs relating to allergic disease. Of the children, 20% were skin-prick positive to at least one of the allergens, and 20% had symptoms of allergic disease, but there was no relationship between the symptoms and the prick test results. No relationship was found between the prick test results and any of the following: the length of time a child was breast-fed; the age of the child and his month of birth. Of the boys, 19% admitted to smoking cigarettes, as did 11% of the girls.

Adolescent↗
PubMed1981

Exercise-induced asthma in Nepalese children.

Three hundred and one children between 5 and 15 years old in the hills of east Nepal were studied to determine the prevalence and the main causes of asthma and atopy. Asthma was diagnosed on the basis of history, clinical examination and the results of a 6-min exercise test (step test). Asthma was diagnosed in six children, none of whom was skin prick test positive. We present here normal values of baseline peak expiratory flow rate (PEFR), and the exercise-induced changes in PEFR in normals, asthmatics, other wheezy children and others with atopic histories. The results of the skin prick tests are presented with the atopic histories in another paper.

Adolescent↗
PubMed1980

Genetic polymorphisms in isolated Sherpa populations of Nepal.

Data are reported on the incidence of variants in the ABO blood group system, four red cell enzyme polymorphisms, and the PTU taster/non-taster polymorphism in 155 Sherpas and Tamangs living in two villages in the isolated Rolwaling valley in east Nepal. The incidence of phenotype AB was unexpectedly high in one village, as has been reported in some other high-altitude populations: possible causes are discussed. Each of the other polymorphisms has a different pattern of distribution between the populations studied; the Sherpas' allele distribution in the phosphoglucomutase (PGM) system seems to be distinct from the surrounding populations'. ABO gene frequencies suggest affinities between Sherpas in the study villages and old- and new-clan Sherpa populations, respectively, in Solu and Khumbu.

ABO Blood-Group System↗