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Biomedical subjects

N Tandon

Publications and source records attributed to N Tandon.

At least 73 records · Page 4Linked to original sources
PubMed1994

Distribution and relative prevalence of anophelines in district south 24-Parganas, West Bengal, India.

The anopheline survey of district South 24-Parganas revealed presence of sixteen species including Anopheles annularis, An. subpictus, An. fluviatilis, An. varuna, An. culicifacies and An. sundaicus known to be associated with malaria transmission in the country. A total of 14, 12 and 8 species were encountered in cattlesheds (CS) in contrast to 7, 5 and 4 species in human dwellings (HD) during monsoon, winter and summer respectively. The population density of anophelines in CS was significantly higher than in HD in all the three seasons.

Animals↗
PubMed1993

IL-2 receptor-positive intrathyroidal lymphocytes in Graves' disease. Analysis of V alpha transcript microheterogeneity.

There has been considerable interest recently in the possible restriction of the TCR repertoire in autoimmune disorders, because such restriction would have important therapeutic implications. Reports of restriction of the TCR V alpha but not V beta repertoire in the thyroid in Graves' disease could not be repeated in an earlier study. Using RNA derived from matched peripheral blood, thyroid tissue, intrathyroidal lymphocytes (ITL), and IL-2R+ and IL-2R- subpopulations of ITL from Graves' patients, we conducted reverse transcription polymerase chain reaction/Southern blot analysis of TCR V alpha family usage. No evidence was found for V alpha restriction in the IL-2R+ subpopulation of ITL from eight patients, one of whom was operated on within 1 mo of diagnosis. We have further analyzed samples from seven of these patients by resolution on denaturing polyacrylamide gels. Typically, a single dominant band was amplified with surrounding minor bands in a normal distribution. Dominant and minor species were both the result of amplification from in frame V alpha transcripts, and the minor bands were separated in size by increments of 3 bp. We found no evidence for reduced heterogeneity of the V alpha transcripts in ITL or IL-2R+ ITL populations relative to peripheral blood in the vast majority of samples. This therefore suggests that there is little difference between the blood lymphocyte population and the activated T cell population in the thyroid in patients with Graves' disease, and indicates that in autoimmune thyroid disease, this method of analysis is not sufficient to distinguish between autoreactive and bystander T cell populations.

Amino Acid Sequence↗
PubMed1993

The gamma delta T cell repertoire in Graves' disease and multinodular goitre.

gamma delta T cells are a subset of T cells with unknown function, and restriction of the gamma delta T cell receptor (TCR) repertoire has been described in rheumatoid arthritis and multiple sclerosis. Elevated numbers of gamma delta T cells have been reported in the peripheral blood and thyroids of patients with Graves' disease. We have carried out flow cytometric analysis on peripheral blood mononuclear cells (PBMC) and intrathyroidal lymphocytes (ITL) from 12 patients with Graves' disease and nine patients with multinodular goitre (MNG), a thyroid disease of unknown etiology. There was no significant difference between the proportion of gamma delta T cells in the PBMC of Graves' and MNG patients, nor between the PBMC and ITL populations in either patient group. We have also carried out polymerase chain reaction amplification on RNA prepared from matched PBMC, ITL and the activated (CD25+) subset of ITL using six TCR V delta-family specific primers. Although there were differences in the amounts of each V delta transcript amplified from PBMC and ITL, there was no difference between the two patient groups. No consistent differences were therefore found between the gamma delta T cell populations in Graves' and MNG patients, arguing against the direct involvement of this T cell subset in the pathogenesis of Graves' disease.

Blotting, Southern↗
PubMed1993

T cell receptor beta chain gene polymorphisms in Graves' disease.

Graves' disease, or subgroups of such patients with thyroglobulin antibodies or HLA-DR3, have been associated with a restriction fragment length polymorphism of the T cell receptor beta chain constant region gene but not all studies are in agreement. We have examined 58 patients with Graves' disease and found no abnormal distribution of this polymorphism compared to 33 controls. There was also no significant association with the presence of thyroglobulin antibodies or HLA-DR3, even when the results were pooled with previously collected data (N = 90 patients with TG antibody results and N = 128 patients with HLA-DR types). We also found no abnormal distribution of three polymorphisms of the T cell receptor beta chain variable region genes, using probes which span over 600 kb of this complex. These results argue against an association of these allelic variations of the T cell receptor beta chain with Graves' disease.

Alleles↗
PubMed1993

Adhesion molecule monoclonal antibodies inhibit experimental autoimmune thyroiditis.

To examine the role played by adhesion molecules in thyroid autoimmunity, we have assessed the effect of administering monoclonal antibodies (mAb) against intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) in experimental autoimmune thyroiditis, induced by immunizing rats with thyroglobulin in complete Freund's adjuvant. The antibody against LFA-1, but not against ICAM-1, reduced thyroglobulin antibody production (P < 0.01) and both antibodies caused a significant reduction (P < 0.002) in the severity of the thyroidal lymphocytic infiltration. In vitro, both mAb impaired the proliferative response of splenic and lymph node T cells to thyroglobulin, but only the antibody against LFA-1 reduced thyroid cell killing assessed using splenic lymphocytes as effectors. Monoclonal antibodies against both these adhesion molecules appear to inhibit cell-mediated autoimmunity in vivo, but only the LFA-1 mAb reduced the autoantibody response.

Animals↗
PubMed1992

Antithyroid drugs and release of inflammatory mediators by complement-attacked thyroid cells.

Thyroid cells are exposed to complement attack in Graves' disease and Hashimoto's thyroiditis, but are resistant to killing by homologous complement. We have examined the effects of sublethal complement attack on thyroid cells in vitro. Extracellular reactive oxygen metabolites were produced and prostaglandin E2, interleukin-1 alpha, and interleukin-6 were released after complement attack. Cells pretreated with interferon-gamma and interleukin-1 alpha, which increase expression of CD59, were more resistant to these effects of complement. Conversely, blockade of CD59 with monoclonal antibody increased complement-mediated oxygen radical production and release of prostaglandin E2, interleukin-1 alpha, and interleukin-6. The antithyroid drugs methimazole and propylthiouracil abolished or reduced oxygen radical production by complement-attacked thyroid cells and reduced cytokine release. These results suggest that sublethal complement attack in autoimmune thyroid diseases exacerbates tissue injury by causing thyroid cells to release potent phlogistic mediators, although some degree of protection may be afforded in vivo by cytokine-mediated upregulation of CD59. Antithyroid drugs, concentrated within thyroid cells, will prevent the release of these inflammatory molecules, which may in turn explain the amelioration of thyroiditis and remission of Graves' disease after such treatment.

Antigens, CD↗
PubMed1992

The expression and role in T cell adhesion of LFA-3 and ICAM-2 on human thyroid cells.

Thyroid follicular cells from patients with Graves' disease and Hashimoto's thyroiditis express intercellular adhesion molecule-1 (ICAM-1) and this is in part responsible for T cell adherence in vitro. To assess the potential role of other adhesion molecules in autoimmune thyroiditis, we investigated the expression and function of lymphocyte function-associated antigen-3 (LFA-3) and ICAM-2 on thyroid cells. Under basal culture conditions, a mean of 22.7% of Graves' thyroid cells (n = 8) expressed LFA-3 and this was enhanced by a mixture of T cell-derived cytokines and by IL-1, but not by TSH. LFA-3 was also demonstrated on Graves' (n = 4) and Hashimoto (n = 2) thyroid cells by immunohistochemical staining ex vivo. A small number of thyroid cells (mean 5.5%, n = 5) expressed ICAM-2 by flow cytometry but this was not altered by cytokines, and ICAM-2 could only be demonstrated on endothelial cells by immunohistochemical staining. It seems likely that contamination of primary thyroid cultures by such cells accounted for the small number of ICAM-2+ cells found using flow cytometry. Almost all of the cultured cells expressing LFA-3 or ICAM-2 also expressed ICAM-1, as assessed by dual staining. Blocking LFA-1, LFA-3, and ICAM-1 with monoclonal antibodies inhibited the adherence of T cells to thyroid follicular cells in assays of cell clustering; antibodies against ICAM-2 had no effect. These results show that two important adhesion receptor ligands, ICAM-1 and LFA-3, are expressed by thyroid cells in autoimmune thyroiditis and that these are likely to have functional importance in allowing T cells to bind to thyroid cell targets. This may play an important role in the initiation and maintenance of Graves' disease and Hashimoto's thyroiditis.

Antibodies, Monoclonal↗
PubMed1992

Analysis of anti-idiotypic antibodies against anti-microsomal antibodies in patients with thyroid autoimmunity.

Anti-microsomal antibody (AMA) activity was inhibited in 14 of 16 sera and in all 12 IgG preparations from patients with postpartum thyroiditis following incubation with F(ab')2 fragments from normal polyspecific immunoglobulin for therapeutic use (ivIg). Similar results were observed with sera from seven of seven patients with Graves' disease and five of six patients with autoimmune hypothyroidism. Results of these competitive binding assays and affinity chromatography of AMA IgG on Sepharose-bound F(ab'), fragments from ivIg indicated that AMA antibodies reacted with ivIg through idiotypic-anti-idiotypic interactions. Eight out of 10 IgG preparations from patients with autoimmune thyroid disease also showed inhibition of AMA activity when coincubated with autologous IgM at various IgG:IgM molar ratios. These observations suggest that ivIg can inhibit anti-microsomal antibodies through idiotype-anti-idiotype interactions and that such interactions occur with IgM anti-idiotype antibodies in vivo, providing evidence of a role for idiotypic network regulation in the control of thyroid autoimmunity.

Antibodies, Anti-Idiotypic↗
PubMed1992

T cell responses to synthetic TSH receptor peptides in Graves' disease.

Twenty-eight peptides, representing the entire extracellular domain of the TSH receptor, were synthesised to investigate which parts of this autoantigen may be targets for the T cell response in Graves' disease (GD). T cells from 11 of 21 controls and 26 of 36 newly diagnosed GD patients proliferated in response to one or more peptides with a stimulation index (SI) of greater than 2.0 (chi 2 = 2.31, P greater than 0.1). The response of patients and controls to any of the individual peptides was also not statistically different. However, individual patients gave high SIs with certain peptides to which controls either gave an absent or very weak response. HLA-DR3 was not associated with any particular response to TSHR peptides. Three out of seven GD patients whose T cells were evaluated before and after treatment showed a response of this kind only early in the course of their disease. Intrathyroidal T cells from four GD patients did not give a consistent proliferative response to pools of five peptides, and depleting peripheral blood T cells of their CD8+ population did not affect the proliferative response. These results indicate that the T cell response to the TSH receptor in GD does not seem to be directed against any one particular epitope on the peptides we have tested which cover the extracellular domain.

Amino Acid Sequence↗
PubMed1992

Thyroid cells in Graves' disease and Hashimoto's thyroiditis stimulate allogeneic T cells when pretreated with phorbol ester.

OBJECTIVE: To assess the capacity of thyroid follicular cells to function as antigen presenting cells, we have examined their ability to stimulate allogeneic T cells. DESIGN: Thyroid follicular cells were pretreated with interferon-gamma or phorbol myristate acetate, washed thoroughly, and their capacity to induce allogeneic T cell proliferation was determined. PATIENTS: Thyroid cells were prepared using thyroidectomy specimens from eight patients with Graves' disease, one with Hashimoto's thyroiditis and two with non-toxic multinodular goitre. MEASUREMENTS: T cell 3H-thymidine incorporation was measured after a 16-hour incubation period with the isotope, 3 days after co-culture of T cells and thyroid cells. RESULTS: Four of the eight thyroid cell preparations from thyroid autoimmunity patients failed to stimulate T cells, although there was a significant, weak stimulation for the whole group (P < 0.05): interferon-gamma pretreatment had no effect on this. Phorbol myristate acetate pretreatment significantly increased the ability of thyroid cells (from both autoimmune and multinodular glands) to stimulate T cells (P < 0.05); this was time and concentration dependent. Cell fixation after PMA treatment did not abolish this stimulatory activity, which could be transferred by supernatants from unfixed cells; exogenous interleukin-1 did not mimic the activity. CONCLUSIONS: Thyroid cells expressing major histocompatibility complex class II molecules only weakly and inconsistently stimulate allogeneic T cells, compared to thyroid cells pretreated with phorbol myristate acetate, a difference which may be due to the expression of an unidentified co-stimulatory signal induced by phorbol ester.

Antigen-Presenting Cells↗
PubMed1992

Expression and function of membrane attack complex inhibitory proteins on thyroid follicular cells.

Human thyroid cells are resistant to lysis by the homologous membrane attack complex. By immunohistochemical staining we here show that normal thyroid cells and those in Graves' disease and Hashimoto's thyroiditis express two membrane attack complex-inhibiting proteins, CD59 antigen and membrane attack complex-inhibiting protein/homologous restriction factor (MIP/HRF). In vitro, the expression of both molecules was enhanced by interleukin-1 (IL-1), tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma) and cytokine-treated thyroid cells were more resistant to lysis by homologous complement. Blocking experiments with monoclonal antibodies against CD59 antigen and MIP/HRF showed that both molecules contributed but CD59 antigen was the more important in mediating resistance to complement attack. Expression of these proteins may be an important determinant of the severity of tissue injury produced by complement-fixing thyroid peroxidase antibodies in autoimmune thyroid disease.

Antigens, CD↗
PubMed1991

Constrictive pericarditis masquerading as Budd-Chiari syndrome.

Budd-Chiari syndrome (BCS) and constrictive pericarditis (CP) share many common clinical features. Over the last year we encountered three patients in whom CP clinically mimicked BCS. Two of the three did not even have raised jugular venous pressure. One patient with severe jaundice and hepatic coma ultimately died. Liver biopsy features were not discriminating. The final diagnosis of CP was established by echocardiography, chest computed tomography (CT), or cardiac catheterization. We conclude that in all patients with apparent BCS and atypical features, a noninvasive test like echocardiography or chest CT should be done to rule out treatable illness like CP before embarking on such invasive procedures as liver biopsy for diagnosis.

Adolescent↗
PubMed1991

T cell responses to synthetic thyroid peroxidase peptides in autoimmune thyroid disease.

Sixteen peptides, representing four different extracellular regions of thyroid peroxidase (TPO) predicted to contain a high proportion of potential T cell epitopes, were synthesized to investigate which parts of this autoantigen may be targets for the T cell response in thyroid autoimmunity. Compared with 25 controls, peripheral blood T cells from 23-37% of 30 patients with Graves' disease or autoimmune hypothyroidism were stimulated significantly by three peptides, representing amino acids 415-432, 439-457 and 463-481 of the TPO sequence; T cells from individual patients were also stimulated by several other peptides. These results indicate that the T cell response to TPO is directed against several epitopes which may be recognized by different patients.

Amino Acid Sequence↗
PubMed1991

HLA associations with Hashimoto's thyroiditis.

There is disagreement over the HLA-DR associations of Hashimoto's (goitrous) thyroiditis. We have studied 86 English Caucasian patients with this condition whose DR types were determined by restriction fragment polymorphism analysis. HLA-DR3 was significantly more frequent in these patients than in 100 controls (chi 2 = 7.09; P less than 0.01). The relative risk was 2.23 and aetiological fraction 0.29. HLA-DPB and DQB alleles were analysed in a proportion of these subjects by enzymatic DNA amplification and oligonucleotide probing. The only significant finding was an excess of HLA-DQw2 (in linkage disequilibrium with DR3) in the Hashimoto group (chi 2 = 7.43, P less than 0.007). These results do not support a difference between goitrous and atrophic thyroiditis based on respective associations with HLA-DR5 and DR3, but confirm a recent study in which HLA-DR3 was associated with Hashimoto's thyroiditis. However, it is possible that genes telomeric to DR3 may be involved in determining which type of thyroiditis a patient with autoimmune hypothyroidism develops.

Female↗
PubMed1991

Adhesion molecule expression by the FRTL-5 rat thyroid cell line.

We have examined the expression and function of rat CD54, a homologue of human intercellular adhesion molecule-1 (ICAM-1), by the continuously growing rat thyroid cell line FRTL-5. Approximately 10% of FRTL-5 cells express CD54 under basal conditions and this is not influenced by thyrotrophin. Expression of CD54 is increased by cytokines (gamma-interferon, tumour necrosis factor, interleukin-1) and by an activator of C-kinase, phorbol 12-myristate 13-acetate. Blocking ICAM-1 with a monoclonal antibody directed against this molecule significantly (P less than 0.01) reduced the binding of splenic lymphocytes to FRTL-5 cells but inhibition was consistently greater (P less than 0.01) in the presence of antibodies against a rat homologue of lymphocyte function-associated antigen-1, the receptor on T cells for ICAM-1. In no case was complete blocking of cluster formation observed. These results show that a pure line of rat thyroid cells can express an ICAM-1 homologue and this is directly enhanced by cytokines. Expression of this homologue is partially responsible for lymphocyte adhesion to thyroid cells, which is likely to be a major event in T cell recognition of thyroid antigens in autoimmune thyroiditis.

Animals↗