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Biomedical subjects

J R Batchelor

Publications and source records attributed to J R Batchelor.

At least 73 records · Page 4Linked to original sources
PubMed1988

Antibodies against monocytes and endothelial cells in the sera of patients with atherosclerotic peripheral arterial disease.

We looked for antibodies against endothelial cells, monocytes, fibroblasts, lymphocytes and Epstein-Barr virus transformed lymphocytes in the sera of 28 elderly and 18 middle-aged patients with atherosclerotic peripheral arterial disease and 13 controls. Inclusion criteria were symptomatic peripheral arterial disease with intermittent claudication and ankle/radial Doppler pressure ratio less than 0.7 in the patient group and greater than 1 in the controls. The sera were tested using a standard cytotoxic technique against a cell panel of monocytes, T and B lymphocytes from 5 donors, and against endothelial cells, fibroblasts and Epstein-Barr virus transformed lymphocytes from one umbilical cord vein and blood. The sera of 30 of 46 (65.2%) patients showed toxicity against monocytes from at least one member of the cell panel and 12 of 19 sera tested (63%) reacted with endothelial cells. Only one of the control sera was positive against monocytes and none reacted with endothelial cells. None of the sera of either patients or controls contained cytotoxic antibodies against T and B lymphocytes, Epstein-Barr virus transformed lymphocytes or fibroblasts. The selective cytotoxicity suggests that the antibodies detected are not against HLA-antigens (which are expressed by normal lymphocytes and Epstein-Barr virus lymphocytes). Our results suggest that immune phenomena occur in atherosclerosis.

Aged↗
PubMed1988

C4 complement allotypes in juvenile dermatomyositis.

Twenty probands with juvenile dermatomyositis and their relatives were studied to determine the inherited segregation patterns of class I, II, and III HLA region markers including C4A, C4B, Bf, and C2 complement polymorphisms. The extended haplotype B8, DR3, C4A*Q0, C4B*1, C2*C, and Bf*S was present in 13 of the 20 probands. Three other probands also carried a haplotype with a null allele for C4A and two further probands carried a null allele for C4B; only two probands had no detectable C4 null allele. These data confirm previous studies showing high frequencies of B8 and DR3 in patients with juvenile dermatomyositis, but show that there is a higher association with null alleles of C4. This suggests that the C4 genes are either themselves the disease-susceptibility genes or are in very strong linkage disequilibrium with such genes.

Adolescent↗
PubMed1988

Targeting of lymphocytes with 111In-labelled monoclonal antibodies.

In this paper, we emphasize the rationale and work-up studies for using two radiolabelled anti-lymphocyte monoclonal antibodies for in vivo application as radiolabelling agents for T and B cells. In vitro experimental work involved radioimmunoassays on human lymphoid cell lines and anticoagulated whole blood with identification of relevant binding kinetics in terms of antibody internalization and elution. We tested also for the effect of the radiolabelled monoclonal antibodies on in vitro cell function defined as mitogen-induced proliferation in whole blood. As a final work-up in an animal model, the distribution of both unlabelled and 111In-labelled anti-Pan T cell monoclonal antibody was studied in the rat. Results from the in vitro experiments pointed to the possibility of using the described technique for specific lymphocyte radiolabelling. The in vivo application enabled us to identify optimal doses of antibody and radioactivity which showed agreement with the in vitro data.

Animals↗
PubMed1988

The arthropathy of cystic fibrosis.

Musculoskeletal symptoms are frequent in cystic fibrosis (CF). Here the clinical features of 29 patients with CF who had significant arthropathy are described. Twelve had episodic arthritis (EA) characterised by repeated short attacks of severe, incapacitating polyarthritis, which in seven was associated with fever and erythema nodosum. Ten patients had hypertrophic pulmonary osteoarthropathy (HPOA). The onset of symptoms in the group with HPOA was usually later (mean age 20 years v 16 years for EA) and was associated with significantly worse lung function than in patients with CF, either without arthropathy or with EA. Seven patients had arthropathies which could not be classified as EA or HPOA.

Adolescent↗
PubMed1988

Recovery after optic neuritis in childhood.

Thirty-nine children who presented with optic neuritis in childhood were reviewed after a follow up period from 3 months to 29 years (mean 8.8 years). At follow-up, 30 out of 39 (77%) of the children had had no further episodes and in three (8%) there was recurrence of optic neuritis alone. Multiple sclerosis had developed in six patients (15%), a much lower frequency than after optic neuritis in adult life. Regardless of the initial degree of visual impairment or neurological outcome, the visual prognosis was excellent. Pattern evoked potentials at follow-up were much more frequently normal (55%) than in adults (10%) after optic neuritis.

Adolescent↗
PubMed1988

Frequency analysis of cytotoxic T lymphocyte precursors--possible relevance to HLA-matched unrelated donor bone marrow transplantation.

HLA-matched unrelated donor (MUD) bone marrow transplants and transplants between HLA mismatched family members are associated with an increased incidence and severity of graft-versus-host disease (GVHD) in comparison with HLA-identical sibling transplants. A limiting dilution analysis system was set up to measure the frequency of alloreactive cytotoxic T lymphocyte precursors (CTL-p) in normal individuals and in potential donor/patient pairs selected for bone marrow transplantation. The donor/recipient pairs were divided into four groups depending on their degree of HLA disparity. A distinct range of CTL-p frequencies was obtained for each group and these showed a hierarchy of response related to the degree of HLA disparity between donors and recipients in that particular group. This assay system may be of value in selecting potential matched unrelated and mismatched family donor/patient pairs for those at lower risk of GVHD.

Analysis of Variance↗
PubMed1988

Lymphocyte targeting with 111In-labelled monoclonal antibodies.

In vitro tests were conducted using human T and B cell lines, as well as whole blood, to establish the usefulness of 2 murine monoclonal antibodies (MAbs), an anti-CD5 (Pan T) and a Pan B, for potential radioimmunolocalization and therapy. Both MAbs showed specificity for the cell line in question as tested by indirect immunofluorescence and radioimmunoassay. Assays carried out on whole blood showed 40-70% of the added activity of 111In-labelled Pan B antibody binding to B cells and 20-24% of 111In-Pan T antibody binding to T cells. The amount of internalised 111In-labelled Pan B was 6% of total amount at 24 hr indicating a slow internalisation process. These results should allow for in vivo targeting of normal and neoplastic B and T cells.

Animals↗
PubMed1987

Multiple sclerosis in north-east Scotland. An association with HLA-DQw1.

This study reports the frequencies of HLA antigens and the polymorphic variants of C4, C2, and Bf for 200 patients with multiple sclerosis (MS) living in the Grampian region of Scotland, an area of high disease prevalence. A group of 128 normal subjects from the same region were typed for comparison. Although the frequencies of HLA-B7 and DR2 in the patient group (43.3% and 49.4%, respectively) were found to be similar to those reported for other Northern European HLA studies on patients with MS, high frequencies of these antigens were also observed in the group of normal Grampian subjects (38.3% and 40.6%) the differences were not statistically significant. However, a significant association was found between the recently defined Class II HLA antigen, DQw1, and MS (P less than 0.006) when compared with controls. There were no significant differences in frequency of the polymorphisms of C4, C2, and Bf when the group of patients with MS was compared with the control group of normal subjects. The patients were subdivided according to disease severity, remittent versus progressive clinical course, age of onset of the disease and initial symptoms. The frequencies of the HLA and complement polymorphisms (C4, C2, and Bf) were analysed in these subdivisions. DQw1 was found with similar frequency in severe and benign disease (78% and 80%, respectively) but DR2 was most frequent in the group of patients with remittent disease (54%). There were no significant differences in frequency of the polymorphisms of C4, C2, and Bf between the above subgroups of patients and overall no significant HLA associations were found with age of onset of disease or initial symptoms. The findings suggest that in an area of high prevalence of MS, the disease is more closely associated with DQw1 than DR2. Furthermore, there was no evidence to support the hypothesis that the HLA region complement gene polymorphisms show significant association with a putative HLA-linked MS susceptibility gene.

Complement C4↗
PubMed1987

Retinal venous sheathing in optic neuritis. Its significance for the pathogenesis of multiple sclerosis.

A systematic study of the frequency of retinal vascular abnormalities and cells in the media has been made in 50 patients presenting with acute optic neuritis. Abnormalities were found in 14 (fluorescein leakage in 10, perivenous sheathing in 6, cells in the vitreous in 6 and in the anterior chamber in 4; in 2 the cells in the media were seen without vascular changes). After a mean follow up of 3.5 years multiple sclerosis (MS) had developed in 8/14 patients with vascular abnormalities and/or evidence of inflammation and in 5/32 without; the difference is significant (P less than 0.02). The occurrence of perivenular abnormalities in a region free of myelin and oligodendrocytes provides evidence that the vascular changes in MS can occur independently of contiguous demyelination, and may be the primary event in the formation of a new lesion.

Adolescent↗
PubMed1987

Analysis of the alloreactive T cell repertoire in man. I. Differences in precursor frequency for cytotoxic T cell responses against allogeneic MHC molecules in unrelated individuals.

We demonstrate here that in man the frequency of cytotoxic T cells specific for a given set of allo-major histocompatibility complex (MHC) antigens varies among unrelated individuals. This has been established by limiting dilution analysis of human peripheral blood lymphocytes (HPBL) in the presence of irradiated autologous filler cells, T cell growth factors, and irradiated HPBL carrying allo-MHC antigens. Two unrelated individuals were tested against the same panel of allo-MHC antigens. We have been able to identify frequencies of T cells ranging from 1:5,000 to 1:20,000(high), 1:20,000 to 1:60,000(intermediate) and 1:60,000 to 1:100,000(low). In some cases, the precursor frequency of cytotoxic T cells was so low that it was considered to represent nonresponsiveness. The clear differences in precursor frequency suggest that this system is suitable for further analysis of the allo-MHC-specific repertoire in man.

Cells, Cultured↗
PubMed1987

A reassessment of the risk of multiple sclerosis developing in patients with optic neuritis after extended follow-up.

One hundred and one of 146 patients presenting with isolated idiopathic optic neuritis, previously reviewed in 1978, were reassessed clinically, and retyped for HLA antigens and Factor B alleles, after a mean follow-up of 11.6 years. Fifty eight patients (57%) had developed multiple sclerosis at the time of reassessment in the present study, of whom 51 (88%) had clinically definite disease. This compared with 40% of the original group, in 1978, of whom 62% then had clinically definite multiple sclerosis. When the life-table method of analysis was used, the probability of developing multiple sclerosis was 75%, 15 years after the initial episode of optic neuritis. The frequencies of HLA-DR2 and the recently defined D-region antigen, DQw1, were significantly increased in patients with isolated optic neuritis and those who subsequently developed multiple sclerosis compared with normal controls, but neither allele appears to influence progression from optic neuritis to multiple sclerosis. Patients with optic neuritis who were HLA-DR3 positive had an increased risk for the development of multiple sclerosis (RR = 2.8) and this risk was further enhanced when DR3 occurred in combination with DR2 (RR = 6.7). The overall increased risk of developing multiple sclerosis for patients with this combination was 26 times that for the normal population. When the patients' original tissue-typing was considered BT 101 no longer influenced conversion of optic neuritis to multiple sclerosis. This may partly be explained by improved methods of tissue-typing, since not all BT 101 patients were subsequently found to be positive for HLA-DR2 or HLA-DQw1 and vice versa and by extended follow-up as multiple sclerosis conversion in HLA-DR2 negative individuals increased with time. All 101 patients were typed for Factor B alleles. No significant differences in frequencies were found between individuals with isolated optic neuritis or those who progressed to multiple sclerosis compared with the control population. Recurrent episodes of optic neuritis were associated with an increased risk for the development of multiple sclerosis in this study.

Adolescent↗
PubMed1987

Erythrocyte complement receptor type 1 (CR1) expression and circulating immune complex (CIC) levels in hydralazine-induced SLE.

Family studies were carried out to look at CR1 expression in 24 hydralazine-induced SLE patients (Hz Reactors), who had been off the drug for at least 1 year and were clinically well at the time of the study. Mean expression of CR1 was reduced by 27% in the group of hypertensives who had developed Hz-induced SLE compared with a group of 35 normal individuals. CR1 expression was also slightly reduced in the relatives of the Hz Reactors compared to the normal group. Using a solid-phase Clq binding assay, CIC levels were found to be elevated in the plasma of the Hz reactors and an inverse relationship was found between CR1 levels and CIC levels in this patient group. Both CR1 levels and CIC levels in Hz Reactors and normal individuals were constant over the 36 weeks studied. This study suggests that there is an association between an inability to deal efficiently with CIC and susceptibility to developing Hz-induced SLE.

Antigen-Antibody Complex↗
PubMed1987

Combined familial C7 and C4B deficiency in an adult with meningococcal disease.

A case of meningococcal septicaemia is reported in an adult with a deficiency of the seventh component of complement combined with a deficiency of the B locus product of C4. A family study demonstrated that the two deficiencies were not linked. This is the first time that the individual alleles of C4 were determined in a patient with a deficiency of one component of the terminal pathway. It is possible that the heterogeneous clinical picture of a terminal pathway deficiency may, in part, be explained by the co-existence of other subtle complement defects.

Adult↗