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Biomedical subjects

N Tandon

Publications and source records attributed to N Tandon.

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

Continuous hyperfractionated accelerated radiotherapy in advanced head and neck malignancies.

58 patients of advanced head and neck cancer were treated by continuous hyperfractionated accelerated radiotherapy (study group) or conventional radiotherapy (control group). The study group of 29 patients had 26/29 (89%) of patients of stage T3 and T4 with 12/29 (41% 0) > N2 disease. The schedule employed was 1.5 Gy 3 times a day in 36 fractions on 12 treatment days without stopping for weekends. The spinal dose has been kept at 40.5 Gy and interfraction interval has been strictly kept at 6 hrs. Clinical, as well as radiological assessment has been encouraging with 23/29 (79.13%) of patients achieving complete regression of the primary tumor and nodal disease. Compared to the conventionally treated controls this value has been significant (P value < 0.001). In stage III disease tumor control has been in 9/10 (90%) cases, while in stage IV disease in 14/19 (73.68%) cases. The acute mucosal reactions have been found to be severe in these cases with 18/29 i.e. 62.06% suffering from grade III reactions. Nasogastric feeding was required in 25.92% of patients.

Adult↗
PubMed1997

MIB-1 proliferative index in parathyroid adenoma & hyperplasia.

A retrospective study on 22 cases of parathyroid adenoma, 9 cases of primary parathyroid hyperplasia and 14 specimens of normal suppressed glandular tissue was undertaken to determine the usefulness of proliferative index (PI) for discriminating adenoma from hyperplasia, as an adjunct to the existing histological criteria. PI was determined by avidin-biotin-complex immunostaining after high temperature microwave antigen retrieval in paraffin sections, using monoclonal MIB-1 antibody which detects paraffin resistant analogue of cell cycle-associated Ki-67 antigen. PI expressed as percentage positive cell nuclei, was 1.36 +/- 0.62 (range 0.04-2.72) in adenoma, 1.17 +/- 0.83 (0.02-1.98) in hyperplasia and 0.03 +/- 0.02 (0.00-0.06) in normal suppressed glandular tissue. While the difference between normal suppressed glandular tissue and adenoma and hyperplasia was significant (P < 0.001), that between adenoma and hyperplasia was not. We conclude that although PI could distinguish between normal suppressed glandular tissue versus glands with primary hyperparathyroidism, it failed as an additional useful parameter for discriminating between adenoma and hyperplasia, both of which have low but similar proliferative activity.

Adenoma↗
PubMed1995

Up-regulation of intercellular adhesion molecule 1 (ICAM-1) on human renal cell carcinoma cells by interleukin-4.

We have previously demonstrated that human renal cell carcinoma (RCC) cells express high-affinity IL-4 receptors (IL-4R). To study the functions of these receptors, we have examined the effect of IL-4 on the expression of intercellular adhesion molecule-1 (ICAM-1 or CD54) on human RCC cells. Following incubation with various concentrations of IL-4, RCC cells were examined for ICAM-1 expression by flow cytometric analysis. The 2 primary RCC cell cultures and the 2 cell lines examined expressed varying basal levels of ICAM-1 on the cell surface. IL-4 treatment increased ICAM-1 expression in a time-dependent manner and maximum augmentation of ICAM-1 expression was observed after a 48 hr incubation. The increase in ICAM-1 expression was specific because anti-hIL-4 antibody blocked this effect. No enhancement of ICAM-1 expression was observed when RCC cells were incubated with IL-4 in the presence of cycloheximide, indicating that the IL-4 effect requires new protein synthesis. Up-regulation of ICAM-1 expression was also observed at the mRNA level and maximum increase in message occurred 8 hr post-IL-4 treatment. Both IL-4 and IFN-gamma also increased soluble ICAM-1 levels in WS-RCC culture supernatant. The significance of enhanced soluble and surface ICAM-1 expression was investigated by examining the lymphokine activated killer (LAK) cell-mediated lysis of IL-4-treated WS-RCC cells. LAK cells lysed WS-RCC cells very effectively, but lysis observed in target cells pre-treated with IL-4 did not correlate with the increased expression of ICAM-1 antigen. Our results indicate a previously unknown function of IL-4 on RCC and further demonstrate that IL-4R on RCC are functional.

Blotting, Northern↗
PubMed1995

Anopheline fauna of Ajodhya hills, district Purulia. West Bengal.

Anopheline fauna of cattlesheds (CS) in Ajodhya hills, District Purulia, consisted of 12 species during summer, monsoon and 10 species during winter. Of the six vector species encountered in CS, Anopheles culicifacies, An. annularis, An. subpictus, An. maculatus and An. fluviatilis were found in all the three seasons. An. philippinensis was encountered in monsoon only and constituted 0.61% of the total anopheline catch made during the season. An. culicifacies was the most predominant species during summer (MHD 30.38) and monsoon (MHD 11) but ranked third (MHD 9.64) to An. annularis (MHD 16.28) during winter; An. subpictus being second (MHD 10.28) in order of predominance. An. annularis was the second most prevalent vector species in summer (MHD 21.38) and monsoon (MHD 9.92). The population density of the remaining three vector species was extremely low in the two seasons. In human dwelling (HD), of the five anopheline species encountered (An. subpictus, An. annularis, An. culicifacies, An. vagus and An. splendidus), the former three were found in all the three seasons. MHD of An. annularis in HD in summer, monsoon and winter was 3.7, 1.1 and 1.9 respectively, while MHD of An. culicifacies in the corresponding seasons was 5.01, 2.09 and 1.31 respectively.

Animals↗
PubMed1995

The evaluation of skin prick test in house dust mite allergy in Calcutta, India.

Immediate type allergy towards house dust and house dust mites was measured in 188 dust-sensitive asthmatic patients in and around Calcutta by using the skin prick test. Of the 131 positive patients, 82% reacted to Dermatophagoides mites, 80% to D. farinae, 46% to D. pteronyssinus, and 43% to both species of mites. Sixty-two per cent of the positive patients showed strong skin reaction to D. farinae as compared to 32% to D. pteronyssinus. Skin reaction (positive/strong) was highest in D. farinae as compared to other allergens tested in the present study. Skin test results were also analysed in relation to patients' age, sex and duration of disease.

Adolescent↗
PubMed1994

Cloning and analysis of IgM anti-thyroglobulin autoantibodies from patients with Hashimoto's thyroiditis.

Hashimoto's thyroiditis is an autoimmune disease in which autoantibodies reactive to a number of thyroid antigens are made. In order to investigate the autoantibody repertoire in this disease, B cells from four patients with Hashimoto's thyroiditis were immortalised and, after limiting dilution, screened for reactivity to thyroid antigens. After a second limiting dilution, one anti-thyroglobulin IgM-secreting clone from three patients, and four clones from one patient, were analysed. The Ig heavy and light chain genes from each clone were amplified using the polymerase chain reaction and sequenced. The resulting heavy and light chain sequences were heterogeneous, although the four clones from one patient and the clone from a second patient shared a germline VH sequence. All antibodies had similar functional affinity, comparable to serum IgG from Hashimoto's patients. The cross-reactivity of the antibodies was analysed against bovine and rat thyroglobulin, histones, cardiolipin and human skeletal muscle. The antibodies were polyreactive, indicating that they are probably natural autoantibodies of unknown pathogenic significance.

Amino Acid Sequence↗
PubMed1994

Phencyclidine inhibits epinephrine-stimulated platelet aggregation independently of high affinity N-methyl-D-aspartate (NMDA)-type glutamatereceptors.

The psychotomimetic analgesic phencyclidine (PCP), which binds to a high affinity site on the neuronal N-methyl-D-aspartate (NMDA)-sensitive glutamate receptor, has previously been found to bind to platelets with high affinity and to specifically delay the onset of epinephrine-stimulated platelet aggregation (Jamieson et al. (1992) Biochem. J. 285, 35-39). We have now shown that the rank order of binding affinities of 14 synthetic PCP analogs at the high affinity binding site on platelets does not parallel the rank order of their affinities in binding to rat brain membranes, indicating that the high affinity PCP binding sites in platelets is distinct from the neuronal NMDA receptor. The order of potency of six of these analogs in delaying the onset of epinephrine-stimulated platelet aggregation also did not parallel the rank order of their binding affinities for platelet or brain binding sites. These data indicate that the ability of PCP analogs to inhibit epinephrine-stimulated aggregation is not related to their ability to bind to the high affinity platelet PCP binding site. Furthermore, (+)MK-801, which binds to the same high affinity binding site in neurons as does PCP, failed to inhibit epinephrine-stimulated platelet aggregation, further suggesting that the site at which PCP acts in platelets is not related to the NMDA-type glutamate receptor. Further studies showed that 5-HT2 receptors and effects on platelet secretion are not involved in PCP-mediated inhibition of epinephrine-induced platelet aggregation.

Adenosine Diphosphate↗
PubMed1994

T cell responses to orbital antigens in thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) is most likely to be a T cell-mediated disease, in which cytokines released in the extraocular muscles activate fibroblasts, increasing glycosaminoglycan production. The nature of the orbital antigen recognized by the infiltrating T cells is unclear, although it is possible that there is cross-reactivity between this and a thyroid autoantigen to explain the close association with thyroid autoimmunity. We have tested the ability of human and porcine eye muscle antigen preparations to stimulate proliferation of circulating T cells from healthy subjects and patients with TAO or Graves' disease without clinical TAO. Occasional responses were seen, particularly after depletion of CD8+ T cells, and two out of 10 TAO patients responded to eye muscle proteins of 25-50 kD after fractionation of antigens on gels and subsequent elution. There was no disease-specific response of T cells to R1, R14, D1 and 1D3, recombinant proteins identified from screening an eye muscle cDNA library with sera from patients with autoimmune thyroid disease. We have also found that interferon-gamma (IFN-gamma) production by T cells from TAO patients was not stimulated by eye muscle membrane antigens or by 1D3. These results suggest that the frequency of circulating T cells responding to eye muscle antigens in TAO is low, and that several candidate orbital antigens, including the 64-kD protein 1D3, are unlikely to be important T cell autoantigens in this condition.

Animals↗
PubMed1994

Immunoglobulin class and subclass distribution of eye muscle and fibroblast antibodies in patients with thyroid-associated ophthalmopathy.

OBJECTIVE: The investigation of the antibody response in thyroid-associated ophthalmopathy (TAO) using different antigens and assays has given inconsistent results. We have analysed antibodies against eye muscle and control antigens in a large group of TAO patients to assess whether specific eye muscle antibodies exist in TAO. We have also evaluated the presence of IgA and IgM class antibodies and examined IgG subclass distribution. DESIGN: Sera were obtained from all patients (TAO, Graves' disease without ophthalmopathy and Hashimoto's thyroiditis) within one year of diagnosis. Sera were also collected from healthy controls, with no family history of autoimmune thyroid disease. PATIENTS: Thirty-eight patients had Graves' disease with Grade III or greater TAO; 15 patients had Graves' disease without ophthalmopathy and nine had Hashimoto's thyroiditis without any eye signs. The control group consisted of 14 subjects. MEASUREMENTS: Antibodies against porcine eye and skeletal muscle, human eye (membrane and soluble antigen) and skeletal muscle, human thyroid microsomal and thyroglobulin antigens and dermal and orbital fibroblast antigens were assessed using ELISA. Antibody isotypes and IgG subclasses were studied for porcine and human eye muscle antibodies. Eye muscle (porcine and human) and orbital fibroblast antibodies were further analysed by immunoblotting. RESULTS: There were no significant differences in the ability of either IgG or IgA in sera from the different groups to bind porcine and human eye muscle antigens. There was a significant correlation (P < 0.0001) between the binding to porcine eye muscle and skeletal muscle antigens (for both IgG and IgA). There was no difference between sera from TAO patients and control subjects in their binding to eye muscle fibroblasts for both IgG and IgA antibodies. However, IgA antibody activity against dermal fibroblasts differed significantly between TAO patients and controls (P < 0.05). By immunoblotting, the frequency of IgA antibodies recognizing 21 kDa (40% of patients) and 62 kDa (52%) bands in porcine eye muscle blots and 20, 24 and 38 kDa bands in blots of human eye muscle (soluble) antigen differed significantly between patients with TAO and controls (P < 0.05 in all cases). IgG antibodies recognizing 80 and 92 kDa bands in blots of the subcellular membrane antigen prepared from orbital fibroblasts were found more frequently in patients with TAO compared with controls (P < 0.05 in both cases). CONCLUSIONS: We found no evidence that eye muscle membrane or fibroblast antibodies are present in a significant proportion of TAO patients, using ELISAs based on antigens prepared from several sources. We have also failed to demonstrate the presence of previously described specific, TAO-associated antibodies, including those directed against a 64 kDa protein in eye muscle and a 23 kDa protein in fibroblasts. IgA class antibodies reactive with orbital components appeared to be more strongly associated with TAO than those of the IgG class, though even this relationship is weak. These results suggest that antibodies are of secondary importance in the pathogenesis of TAO, which is most likely a T cell-mediated disorder.

Animals↗
PubMed1994

Expression of the costimulatory molecule B7/BB1 in autoimmune thyroid disease.

Efficient antigen presentation requires the provision of a costimulatory signal, the best characterized of which is B7/BB1. It is unclear whether thyroid cells expressing class II molecules can present autoantigens to T cells, although this has been suggested as an important mechanism in the initiation of Graves' disease and Hashimoto's thyroiditis. We have found that thyroid cells from patients with thyroid autoimmunity do not express B7/BB1 in vivo or in vitro, even after activation with the cytokines interleukin-1 or gamma-interferon, or with a phorbol ester. Increased numbers of CD20+ B cells and CD14+ dendritic cells expressing B7/BB1 were found in intrathyroidal lymphocyte preparations from such patients compared to peripheral blood. These results suggest that conventional antigen-presenting cells rather than thyroid cells provide B7/BB1 costimulatory activity in autoimmune thyroid disease, and argue against a role for the thyroid cells themselves in autoantigen presentation to T cells via the B7/BB1 pathway.

Antigens, CD↗
PubMed1994

Expression and function of multiple regulators of complement activation in autoimmune thyroid disease.

Membrane attack complexes of complement occur around thyroid follicles in Graves' disease and Hashimoto's thyroiditis. The lytic potential of such complexes is controlled by membrane-bound and fluid phase regulators and we have investigated the role of these in autoimmune thyroid disease. By immunohistochemical staining, clusterin and S-protein were found in all nine thyroid specimens from patients with Graves' disease and S-protein was found in one of two Hashimoto glands. CD46, CD55 and CD59 were found on thyroid cells in all specimens. CD46 and CD55 expression occurred on thyroid cells cultured in vitro and was increased significantly by culture with interleukin-1 (IL-1) and interferon-gamma (IFN-gamma), which are known to be released by the lymphocytic infiltrate in these conditions. Blocking CD55 had a weak and inconsistent effect on complement-mediated thyroid cell killing in vitro but, in four of five experiments, blocking CD46 enhanced killing. However, the effect of blocking CD59 was greater in all cases than blocking CD46 or CD55. Expression of these fluid phase and membrane-bound proteins may be important in determining the severity of thyroid damage produced by complement fixation in Graves' disease and Hashimoto's thyroiditis.

Antigens, CD↗