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Biomedical subjects

P Yates

Publications and source records attributed to P Yates.

At least 73 records · Page 4Linked to original sources
PubMed1992

Failure of blood mononuclear cells from human donors with autoimmune haemolytic anaemia to reconstitute severe combined immunodeficient mice.

The use of severe combined immunodeficient (SCID) mice to study humoral responses by peripheral blood mononuclear cells (PBMC) from patients with autoimmune haemolytic anaemia (AIHA) was assessed. Upon transfer to SCID mice, PBMC from normal donors and patients with autoimmune thyroid disease (AITD) produced substantial levels of immunoglobulin (Ig), detectable in the plasma of recipient SCID mice. In contrast, the majority of PBMC from AIHA donors did not produce Ig in recipient mice. The capacity of PBMC to reconstitute SCID mice was not related to the donor's age. In one case, remission of AIHA allowed the donor's PBMC to successfully reconstitute SCID mice, despite the fact that the donor had developed immune thrombocytopenic purpura (ITP). AIHA PBMC were viable by dye exclusion and contained cells in various states of activation, as judged by their IgG secretion profiles when cultured in vitro. The proportions of leukocytes in AIHA PBMC (T to B cell ratios, CD4+ to CD8+ cell ratios and monocytes) were highly variable compared to non-AIHA PBMC. To determine the effect of abnormal lymphocyte proportions on SCID reconstitution, depletion experiments were carried out on normal and AITD PBMC. This work demonstrated a requirement for high T cell numbers, especially CD4+ cells, and minimal B cell numbers for successful reconstitution. CD8+ depletion of PBMC led to increased levels of Ig production in some instances. It is considered that PBMC from AIHA patients have a defect different from that of other autoimmune disorders, which renders them incapable of reconstituting SCID mice.

Adolescent↗
PubMed1991

Chlorinated solvents: will the alternatives be safer?

Over the next decade, use of chlorinated solvents, a widely employed class of chemicals, will decline significantly because of increasingly stringent environmental regulations. These solvents pose certain health and environmental problems and they have been heavily scrutinized. The alternatives to the solvents are being adopted without controls. In some cases, these substances will pose other health and environmental problems that are likely to be as serious; in other cases, the alternatives have not been examined for their health and environmental effects at all. This case study demonstrates that regulations on chlorinated solvents and their potential alternatives are inconsistent with one another and conflicting.

Air Pollution↗
PubMed1991

Direct isolation in eggs of influenza A (H1N1) and B viruses with haemagglutinins of different antigenic and amino acid composition.

Influenza A (H1N1) and influenza B viruses from clinical samples were isolated in the amniotic cavity of embryonated hens' eggs by classical techniques and propagated in the allantoic cavity. Virus progeny from different eggs which had been inoculated with virus material from the same clinical sample possessed antigenically distinguishable haemagglutinins (HAs). Virus progeny of some eggs possessed HAs which were serologically identical to those of virus isolated in parallel in mammalian (MDCK) cells. These egg-grown viruses possessing HAs with the antigenic phenotype of mammalian cell-grown viruses appeared to be antigenically related to epidemic influenza virus because post-infection human sera reacted to high titre with the virus HA. Specific nucleotide changes were detected in the HAs of the viruses isolated directly in eggs at positions 163 and 189 for influenza A (H1N1) viruses or positions 141 and 196 to 198 for influenza B viruses. Egg-isolated viruses which possessed the antigenic phenotype of mammalian cell-grown viruses retained glycosylation sites at positions 163 and 196. The viruses isolated directly in embryonated hens' eggs which possessed the HA antigenic phenotype and glycosylation sites of MDCK cell-grown virus can, unlike the latter viruses themselves, be used as candidate influenza vaccine viruses.

Amino Acid Sequence↗
PubMed1991

Severe combined immunodeficient (SCID) mice: a model for investigating human thyroid autoantibody synthesis.

We have studied the ability of lymphocytes from the blood, thyroid and lymph nodes of patients with autoimmune thyroid disease (AITD) to produce autoantibodies to thyroglobulin (Tg) and/or thyroid peroxidase (TPO) in SCID mice. Human IgG class Tg and/or TPO antibodies were detectable in plasma from SCID mice 7 days after transfer of 15-25 x 10(6) cells/mouse and the highest levels were recorded 2-3 weeks later. In contrast, Tg and/or TPO antibodies were undetectable in recipients of lymphocytes from thyroid antibody negative controls. AITD thyroid lymphocytes produced the most antibody in recipient mice and lower levels were observed in recipients of AITD blood and lymph node lymphocytes. The amounts of Tg and/or TPO antibody detected were in accordance with the ability of thyroid and lymph node lymphocytes to secrete these autoantibodies spontaneously in culture (indicating the presence of cells activated in the patient) and with the capacity of blood lymphocytes (probably B memory cells) to secrete Tg and/or TPO antibodies in culture in response to pokeweed mitogen. Tg antibodies in plasma from SCID recipients of thyroid lymphocytes were of subclasses IgG1, IgG2 and IgG4 and the proportions closely resembled those of the donor's serum Tg antibodies. Blood lymphocytes transferred to SCID recipients were also able to produce Tg antibodies of subclasses 1, 2 and 4 but the subclass distribution varied between mice and the reason for this is not clear at present. Since SCID mice provide an environment in which B lymphocytes from patients with AITD can be activated without mitogen to secrete thyroid antibodies, this model will provide a powerful system for elucidating the mechanisms regulating the secretion of human antibodies to Tg and TPO.

Animals↗
PubMed1991

Mesenteric venous thrombosis due to protein C deficiency.

Protein C deficiency is a known underlying risk factor for thromboembolic disease. Most commonly it presents as thrombophlebitis, deep venous thrombosis or pulmonary embolism. Less common presentations are becoming increasingly recognized now that assays for protein C are more widely available. We present two cases of mesenteric venous thrombosis who were found to have protein C deficiency.

Adult↗
PubMed1989

Protein and nucleic acid analysis of influenza B viruses isolated in Italy in 1984.

Genomic and phenotypic analysis of 30 influenza B viruses, isolated in Italy in 1984, antigenically closely related to the B/USSR/100/83 prototype virus, was carried out using T1-oligonucleotide fingerprinting of total RNA and one-dimensional peptide mapping. The results of fingerprinting analysis indicated an oligonucleotide spot homology of 90-96%, corresponding to a nucleotide sequence variation of only 0.75-0.3%. All the strains appear to belong to the same evolutionary line. Nevertheless, heterogeneity was found at the structural and antigenic level, when the viruses were compared by peptide mapping and monoclonal antibody analysis. No correlation between the biochemical variability of the viruses and the epidemiological characteristics of the different strains was established, which is consistent with the hypothesis that distinct variants, arisen at different times from a parental strain, co-circulate during an epidemic, although the additional occurrence of random mutations during the evolution of the epidemic cannot be excluded.

Antibodies, Monoclonal↗
PubMed1989

Agranulocytosis caused by dapsone therapy for granuloma annulare.

Dapsone has been suggested as a useful drug in the treatment of granuloma annulare; however, adverse reactions include a potentially life-threatening agranulocytosis. We report the case of a 50-year-old woman in whom agranulocytosis and septicemia developed after 7 weeks of therapy with dapsone for granuloma annulare. Full recovery followed cessation of this drug, but caution is advised in prescribing dapsone for relatively benign skin conditions.

Agranulocytosis↗
PubMed1989

The development of Chlamydia trachomatis inclusions within the host eukaryotic cell during interphase and mitosis.

The dynamic nature of Chlamydia trachomatis inclusions was studied by video and 35 mm time-lapse photomicrography of live cells, and by immunolocalization of inclusions in fixed cells. A serotype E isolate was used to infect the MCCoy cell line and endometrial epithelia. Then resulting inclusions were observed over 4 d. They appeared as slowly expanding fluid-filled membrane vesicles whose growth varied considerably, and which were subject to great physical distortion by the host cell during interphase and mitosis. When this distortion became extreme the inclusion was observed to divide. However, as inclusions were mobile within the cytoplasm and thus able to come into contact with each other, there was a net tendency for the opposite process of inclusion fusion to occur when cells contained more than one inclusion. The proportion of infected cells decreased with time as a result of host cell proliferation, despite transmission of inclusions to progeny at the time of mitosis. Inclusion growth physically disrupted karyokinesis and cytokinesis so that host cell division became distorted or blocked on the second or third day of infection. Cell death eventually occurred by a very rapid lysis event.

Cell Line↗
PubMed1988

An in vitro model of Chlamydia trachomatis infection in the regenerative phase of the human endometrial cycle.

An in vitro model of the regenerative phase of the human endometrial cycle was developed in order to study the growth of Chlamydia trachomatis during the period following menses. Glandular epithelial fragments were prepared from curettings of endometria and explanted onto coated substrata. Epithelial cells migrated rapidly from the explant in a fashion which closely mimicked the regeneration of the surface epithelium after menses. The cultures were then experimentally infected with C. trachomatis serotype E at various times during formation of the outgrowth. Chlamydial inclusions developed both within the explants and in the outgrowing epithelial sheets. They were also found in isolated epithelial and non-epithelial cells. However, the most striking feature of chlamydial inclusion development within these cultures was the tendency for inclusions to be located in cells at the periphery of the epithelial sheets. This was partly due to the failure of the cells within the sheets to bind chlamydiae after centrifugation of the organisms onto the culture and partly due to a phenomenon similar to phagokinesis. During this process infectious chlamydial particles were cleared from the substratum by migrating cells with free motile edges, which occasionally led to internalization and inclusion development within these cells.

Cells, Cultured↗
PubMed1987

The receptor-binding and membrane-fusion properties of influenza virus variants selected using anti-haemagglutinin monoclonal antibodies.

A monoclonal antibody raised against X-31 influenza virus reacted with the majority of natural H3N2 viruses isolated between 1968 and 1982. A number of variants of X-31 and of a receptor-binding mutant of X-31 were selected by the antibody during virus replication in eggs and MDCK cells. Antibody-binding assays indicated that the viruses selected were not antigenic variants and analyses using derivatized erythrocytes showed that their receptor-binding properties differed from those of the parent viruses. The amino acid substitutions in the variants were all located in the vicinity of the receptor-binding site and the structural consequences are discussed in relation to the three-dimensional structure of X-31 HA. In addition all of the variants fused membranes at higher pH than wild-type virus indicating that structural modifications in the distal globular region of HA influence the low pH-induced conformational change required for membrane fusion.

Animals↗
PubMed1987

Pyoderma gangrenosum and myelodysplasia.

Pyoderma gangrenosum has been recognized occurring in association with acute and chronic leukaemia. More recently it has been described in patients with myelodysplasia (Jacobs, Palmer & Gordon-Smith 1985). We report a case of pyoderma gangrenosum in a patient with a preceding history of myelodysplasia, illustrating the problem of controlling the skin disease in this condition and the eventual transformation of the myelodysplasia into acute leukaemia. Treatment of the leukaemia resulted in improvement of the skin lesions.

Humans↗
PubMed1987

Tryptase and kinin generation: tryptase from human mast cells does not activate human urinary prokallikrein.

The effect of tryptase, a neutral protease released from human lung mast cell secretory granules, on the tissue prokallikrein present in human urine was examined. Tryptase has been shown previously to lack activity against plasma prokallikrein. Purified tryptase was incubated with a concentrated preparation of urinary prokallikrein. No increase in kallikrein-like enzymatic activity or immunoreactive tissue kallikrein was detected. Activation of urinary prokallikrein with trypsin served as a positive control. Furthermore, preincubation of urinary prokallikrein with tryptase did not diminish the subsequent activation of urinary prokallikrein by trypsin. Therefore, tryptase neither activates nor destroys human tissue or plasma prokallikreins.

Enzyme Precursors↗
PubMed1987

Serological studies with influenza A(H1N1) viruses cultivated in eggs or in a canine kidney cell line (MDCK).

Pairs of influenza A(H1N1) viruses cultivated from the same clinical specimen in canine kidney (MDCK) cells or in embryonated hens' eggs can frequently be distinguished by their reactions with monoclonal antibodies to haemagglutinin and with antibodies in ferret or human sera. Egg-adapted virus, further passaged in MDCK cultures remained "egg-like" in serological characteristics indicating that the differences in their serological reactions were not a direct result of host cell-dependent glycosylation of the haemagglutinin. Haemagglutination-inhibiting (HI) or virus neutralizing antibodies in human sera can be detected more frequently, and to higher titre, in tests employing virus grown exclusively in MDCK cells than in tests with virus adapted to growth in embryonated eggs. Striking differences were detected in the serological reactions in HI tests when sera from ferrets infected with egg-grown virus were tested against a series of strains of influenza A(H1N1) virus isolated in 1983 and adapted to growth in eggs. In contrast, sera from ferrets infected with MDCK-derived virus failed to distinguish serologically between the same viruses that had been passaged exclusively in MDCK cells and also revealed relatively small differences between their egg-adapted counterparts.It was concluded that the cell substrate used for virus isolation and cultivation is a factor that should be considered when interpreting the results of strain characterization of influenza A(H1N1) isolates and in sero-surveys using these viruses.

Influenza A Virus, H1N1 Subtype↗