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T Bourne

Publications and source records attributed to T Bourne.

At least 55 records · Page 3Linked to original sources
PubMed1998

Spontaneous immunoglobulin-producing capacity of cultures from lupus patients and normal donors following depletion of cells expressing CD19 or CD38.

Cells spontaneously secreting IgG or IgM (ISC) are present at a high level in the blood of patients with systemic lupus erythematosus (SLE). By use of magnetic-bead techniques, mononuclear cells from such patients and healthy donors were fractionated according to expression of CD19 or CD38 and the cell fractions were then cultured in the absence of added mitogen/antigen for 5/6 days. Supernatant IgG and IgM were determined and, in addition, in the CD38 experiments ISC were enumerated both before and after culture. Much of the immunoglobulin-producing capacity of unfractionated cells (UFC) from both donor groups was recovered in the CD19- fraction, and no immunoglobulin was produced by CD19+ cells suggesting, unexpectedly, that ISC were not expressing CD19. By contrast, CD38 fractionation resulted in nearly all ISC passing to the CD38+ fraction which produced levels of immunoglobulin approaching 50% that of UFC. On culture of CD38- cells there was a build up in the number of IgG and IgM ISC, this being particularly striking in the controls with numbers well in excess of those in UFC. Not all these new ISC became CD38+, but the maturation process was more efficient in the SLE patients. The possibility is discussed that the spontaneous response in the CD38- populations is due to removal of CD38+ natural killer (NK) cells. Removal of ISC that are present preculture is a helpful initial step in studying ISC generation in the disease.

ADP-ribosyl Cyclase↗
PubMed1998

Six unrelated HLA-DR-matched adults recognize identical CD4+ T cell epitopes from influenza A haemagglutinin that are not simply peptides with high HLA-DR binding affinities.

Influenza A/Beijing/32/92 (H3N2) haemagglutinin (HA)-specific short-term CD4+ T cell lines were generated from six unrelated HLA-DR0701, 1501 positive adults (aged 27-60 years) 3 months following administration of an influenza subunit vaccine containing HA A/Beijing/32/92. Epitope recognition was examined using 118 HA A/Beijing/32/92-specific 16mer peptides which overlapped by 11 residues and which spanned the entire molecule. Following influenza vaccination the donors recognized identical HA peptides. The selected peptides represented HA regions which have been free from extensive drift mutation since the emergence of human H3N2 influenza A strains. Using DAP DR7.0701 cells (a murine cell line expressing HLA-DR0701) as antigen-presenting cells the majority of CD4+ T cell responses were shown to be HLA-DR0701 restricted. The relationship between HA peptide recognition and relative strength of HA peptide-HLA-DR0701 binding was then explored in a competition assay with biotinylated CLIP peptide. Although peptides representing dominant HA epitopes bound to DR0701, the relationship between relative strength of binding and immunodominance was complex, and many strongly binding peptides, particularly those with glycosylation sites and showing inter-strain variation, were not recognized. These results illustrate the control HLA class II exerts over CD4+ T cell HA epitope selection in unrelated adult humans. Immunodominance appears not to be directly related to the relative strength of HA peptide-HLA class II binding, and thus reflects complex interactions between antigen processing, intracellular competition for HLA binding, TCR repertoires and repeated exposure to different strains of influenza A viruses.

Adult↗
PubMed1997

Ultrasound in gynecology: endometrium.

With the development and clinical application of transvaginal transducers/probes (TVS) the sonographic imaging of the endometrium was greatly enhanced compared with abdominal ultrasound. Also, the discomfort of a full bladder associated with abdominal ultrasound could be avoided. A shorter distance between probe and target allowed the use of higher frequency transducers, thereby achieving improved imaging. This review will only discuss the use of TVS, but it does not mean that abdominal ultrasound should not or cannot be used when dealing with the postmenopausal uterus. Transvaginal sonography (TVS) provides a valuable tool for the diagnosis of a wide range of gynecological disorders including those of the uterus and endometrium. The ability of TVS to depict the thickness and morphology of the endometrium has been established in both office and hospital settings. This article will discuss and illustrate the clinical and research applications of transvaginal sonography in relation to the endometrium in both symptomatic and asymptomatic postmenopausal women. The article is of particular relevance today given the number of women who are undergoing transvaginal ultrasonography in the absence of symptoms as a part of their routine check ups. There is a paucity of data relating to the management of apparent ultrasound abnormalities in such women. In symptomatic women or for women at risk of developing endometrial pathology, a technique that could reduce the number of biopsy procedures would be of value. Hysteroscopy, dilatation and curettage (D & C) as well as other endometrial sampling methods are all invasive, thus it would be of benefit if a way could be found to assess the endometrium using a relatively non-invasive approach. Such a technique would need to be relatively easy to learn and perform, as well as being well accepted by the patients. We believe that transvaginal sonography fulfills many of these requirements, the following review will attempt to put forward some of the evidence to support this view.

Endometrium↗
PubMed1996

From epitopes to peptides to immunotherapy.

Allergic inflammatory responses are regulated by cytokines [interleukin (IL)-4, IL-5, IL-10, and IL-13] produced by CD4+ helper (Th0 and Th2) cells. The activation of these T cells follows engagement of T-cell antigen receptors (TCR) by antigenic peptides complexed with major histocompatibility complex (MHC) class II molecules. Under defined conditions presentation of T-cell epitopes as peptides can downregulate immune responses, and here we discuss the potential of peptide-mediated immunotherapy in the regulation of responses to the house dust mite (HDM). Cloning the major allergens of HDM has allowed detailed analysis of the HDM-reactive T-cell repertoire and has revealed that MHC class II restriction is heterogeneous, involving HLA-DP,-DQ, and -DR molecules, and that multiple T-cell epitopes are recognized. There is, however, evidence for a bias in TCR gene usage, which has prompted the analysis of peptide-mediated densitization of human T cells in vitro. CD4+ T cells exposed to high concentrations of HDM peptides become refractory to restimulation and fail to provide B-cell help. This is accompanied by complex changes in the surface phenotype, including the downregulation of TCR and CD28. During the induction of anergy cytokine-specific mRNA levels are enhanced, but when the anergic T cells are restimulated they fail to secrete IL-4 and IL-5, although interferon (IFN)-gamma production may remain unaltered. The ability of peptides to modulate the function of HDM-specific T cells in vivo has been investigated in mice. Following inhalation of peptide containing a major T-cell epitope of Der p 1 (residues 111-139) transient T-cell activation was observed prior to the inhibition of responses in naive and sensitized mice. T cells from the tolerant mice restimulated in vitro produced low levels of cytokines and failed to provide help for B cells.

Adjuvants, Immunologic↗
PubMed1996

B lymphocyte hyperactivity in families of patients with systemic lupus erythematosus.

Blood cells spontaneously secreting IgG and IgM and the level of plasma immunoglobulins and antibodies to dsDNA, ssDNA and influenza virus haemagglutinin have been determined in families of patients with SLE, in 'normal' families and groups of 'normal' individuals. IgM values were consistently higher in females than in males. About one in three of healthy blood relatives gave values in excess of the sex-matched control range in one or more of these test, particularly notable being raised values of IgG anti-dsDNA and total IgG shown by female relatives. High-scoring relatives were more likely to be offspring or parents than siblings of patients, suggesting, together with evidence from a spouse group, the involvement of environmental as well as genetic factors in these families. Correlation analysis between the various assays in the different groups showed a clear distinction between the female control group, where there were no associations, and the female relative group where there were strong associations, including a significant correlation between IgM and IgG antibodies to dsDNA. The male groups produced a more variable picture but the patients gave a remarkably consistent pattern of moderate positive associations. Pokeweed mitogen induced a higher level of IgG production in blood cells of relatives than in controls. These findings are suggestive of a breakdown in relatives of normal antibody regulation. Investigation of immunological abnormalities in family members provides a powerful tool for the analysis of a complex disease.

Adolescent↗
PubMed1996

Hormone replacement therapy after transcervical resection of the endometrium.

OBJECTIVE: To determine if women who have undergone transcervical resection of the endometrium can be treated safely with estrogens alone. METHODS: Sixty-two postmenopausal women who had undergone endometrial resection were recruited into a double-blind, randomized study. Twenty-one had menopausal symptoms at the primary operation and were recruited at the time of the surgery, and 38 were recruited an average of 20 months (range 8-42) after the primary endometrial resection and underwent a second resection to remove any residual endometrium before entering the study. Three patients were excluded from the study. Subjects were allocated randomly to one of two hormone replacement therapy (HRT) regimens: 17-beta-estradiol 2 mg alone or combined with norethisterone 1 mg. Clinical and ultrasound data were collected every 3 months. Hysteroscopically standardized endometrial biopsies were taken after 1 year. RESULTS: In the single-agent therapy group, endometrial hyperplasia without atypia was found in six subjects and proliferative endometrium in eight after 1 year. No such cases occurred among women receiving combined therapy. Endometrial thickness and menstrual bleeding were significantly greater in the single-agent therapy group than in those receiving combined therapy. These differences between single-agent and combined therapy were statistically significant. CONCLUSION: Postmenopausal HRT in patients who have undergone transcervical resection of the endometrium should include progestagen for protection of the endometrium.

Adult↗
PubMed1996

Induction of T cell responses to the invariant chain derived peptide CLIP in mice immunized with the group 1 allergen of house dust mite.

In this study we demonstrate that immunization of H-2(b) mice with the allergen Der p 1 induces MHC class II restricted T cells that proliferate to residues 15-29 of Der p 1 (p15-29) and to the murine MHC class II-associated invariant chain derived peptide (CLIP). T cells from naive H-2(b) mice and those immunized with murine CLIP fail to respond to either CLIP or p15-29. T cell lines and clones reactive with p15-29 strongly proliferate in response to splenic antigen-presenting cells (APC) from normal H-2(b) mice but show reduced proliferation to APC from invariant chain deficient mice. Furthermore, T cells isolated from Der p 1 primed mice and expanded on H-2(b) spleen cells in the absence of the p15-29 epitope retained specificity for both p15-29 and CLIP, suggesting that naturally presented self components can act as mimetic peptides and may maintain T cell memory to foreign antigens.

Allergens↗
PubMed1996

Associations between ultrasound indices of follicular blood flow, oocyte recovery and preimplantation embryo quality.

The aim of this study was to elucidate possible relationships between ultrasound indices of follicular blood flow, oocyte recovery and the subsequent production and morphological quality of preimplantation embryos. A total of 27 women with bilateral tubal occlusion, undergoing treatment for infertility by in-vitro fertilization and embryo transfer, contributed data from 29 cycles. Transvaginal ultrasonography with colour Doppler imaging and pulsed Doppler spectral analysis was used to obtain indices of blood flow for each follicle immediately before it was aspirated. The main outcome measures for each follicle were the pulsatility index, peak systolic velocity, recovery or non-recovery of an oocyte and the subsequent production or non-production of an embryo. A total of 126 follicles were studied, 102 oocytes were recovered and 58 embryos (49 at grades I or II) were produced. There were six clinical pregnancies (pregnancy rate 27.3% per embryo transfer, 22.2% per patient). There was a significant correlation (P < 0.0001, chi2 test) between whether or not follicular blood flow was detected and whether or not an oocyte was recovered. The sensitivity of a test based on the presence of detectable blood flow and the subsequent recovery of an oocyte was 74% and the positive predictive value was 93%. The peak systolic velocity (PSV, measured in cm/s, mean +/- SD) in follicles with detectable blood flow was significantly higher in follicles that were associated with the production of a preimplantation embryo (19.7 +/- 10.8) compared with those that were not (9.9 +/- 5.3, P < 0.0001, Student's t-test). There was a 70% chance of producing a grade I or II embryo if the follicular blood velocity was >/=10 cm/s, compared with 14% if the PSV was <10 cm/s, or 18% if no blood flow was detected. We conclude that there is a physiological relationship between follicular blood velocity, oocyte recovery and the production of a high-grade preimplantation embryo, which may form the basis of a useful clinical test.

Adult↗
PubMed1996

Regulation of corpus luteum function in early human pregnancy.

OBJECTIVE: To investigate the capacity of the human corpus luteum (CL) of pregnancy to form cyclic adenosine-3',5'-monophosphate (cAMP) and P in vitro in response to hCG and prostaglandin (PG) E2. DESIGN: Six women undergoing sterilization concomitant with legal abortion and eight women undergoing surgery for ectopic pregnancy were included. Human chorionic gonadotropin was analyzed preoperatively in two serum samples. The CL were excised and luteal specimens were incubated for 2 hours in the presence or absence of hCG or PGE2. The tissue concentrations of cAMP and P concentrations in the incubation media were measured. The in vitro results were correlated to the preoperative daily change in serum hCG. RESULTS: In CL from pregnancies with normally rising serum hCG levels, the addition of hCG in vitro did not affect luteal cAMP or P production. In pregnancies with plateauing and/or decreasing serum hCG levels, the addition of hCG in vitro significantly stimulated cAMP and P formation, and this stimulatory effect correlated significantly with the preoperative daily change in serum hCG. In contrast to hCG, PGE2 had the same stimulatory effect in vitro on CL specimens from both normal and pathological pregnancies. This effect did not correlate with the preoperative daily change in serum hCG. CONCLUSIONS: Prostaglandin E2 stimulates all CL, irrespective of any changes in preoperative serum hCG levels. In contrast, the stimulatory effect of hCG in vitro does not correlate with changes in serum hCG, and thus CL from pregnancies with normally rising serum hCG levels are refractory to hCG in vitro.

Chorionic Gonadotropin↗
PubMed1995

Nocturnal hypoxaemia in late pregnancy.

We have measured arterial oxygen saturation (SpO2) continuously overnight in 13 non-pregnant (NP), 13 pregnant normotensive (NPIH) and 15 pregnant patients with a diagnosis of pregnancy-induced hypertension (PIH). The two pregnant groups did not differ in duration of pregnancy (> 35 weeks) and none was in labour. There was no significant difference in age between these three groups. Mean SpO2 in group NP was 98.5% (range 97-99%). This was significantly higher than that in group NPIH (95.2 (91-98) %) and group PIH (94.9 (89-99) %). In seven pregnant patients, more than 20% of the recording was spent with an SpO2 < 90%. We conclude that a significant number of pregnant women (> 35 weeks' gestation) suffer from prolonged nocturnal hypoxaemia.

Adolescent↗
PubMed1992

Identification and quantification of rodent malaria strains and species using gene probes.

A DNA probe PCsv4 and a subclone thereof PCsv4.1, hybridize specifically to rodent malaria DNA. DNA purified from a small volume (10 microliters) of infected mouse blood was used to determine the composition of the parasite population present. The hybridization signal following PCsv4 probing of slot-blotted DNA correlated directly with parasitaemia. The hybridization pattern and intensity, resulting from probing restriction enzyme digested and Southern-blotted genomic DNA, determined the identity of the infecting parasite line(s), and provided a semi-quantitative measure of parasite burden. Fifteen parasite lines representative of all four Plasmodium species infecting rodents can be differentiated in this way.

Animals↗
PubMed1992

Assessment of parasite population dynamics in mixed infections of rodent plasmodia.

Cloned lines of the four rodent Plasmodium species can be differentiated by the RFLP pattern generated following Southern blotting and probing with PCsv4.1, a probe derived from a P. chabaudi chabaudi genomic library. Groups of CBA/Ca mice were inoculated simultaneously with cloned lines from two parasite species or strains. Six mixed species and three mixed strain infections using rodent malaria lines were initiated. The composition of the parasite population in each group was determined qualitatively and semi-quantitatively by analysis of the DNA purified from daily blood samples, thereby providing a dynamic representation of each mixed infection. Effects on the course of parasitaemias are presented and discussed.

Animals↗
PubMed1991

Ovarian morphology, endocrine function and intra-follicular blood flow during the peri-ovulatory period.

Transvaginal ultrasonography with colour flow mapping has been used to study changes in intra-follicular morphology and blood flow during a peri-ovulatory period in one volunteer. Aspects of uterine morphology and blood flow were also recorded. The intervals from a defined luteinizing hormone (LH) rise and peak to the mean time of follicular rupture were 37.5 and 17.5 h, respectively. Blood flow velocity waveforms were observed clearly at the time of the LH rise and blood vessels were visible when the hormone level reached a peak. Concurrently, the wall of the follicle became less clear, crenated, thicker and more echogenic. A structure resembling the detached cumulus and oocyte was seen before the follicle had ruptured. Peak systolic blood velocity was highest immediately after ovulation had occurred. Blood flow impedance in the uterine arteries suggested the presence of a circadian rhythm, but no pronounced daily changes were observed over the study period. In contrast, flow velocity waveforms were clearly visible in the endometrium around the time of ovulation. These preliminary data suggest that intra-follicular vascularization or angiogenesis may be critical processes that might be used to predict ovulation and could possibly be modified to help achieve or avoid a pregnancy.

Adult↗