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Biomedical subjects

N R Farid

Publications and source records attributed to N R Farid.

At least 19 recordsLinked to original sources
PubMed1992

Typing for major histocompatibility complex class II antigens in thyroid tissue blocks: association of Hashimoto's thyroiditis with HLA-DQA0301 and DQB0201 alleles.

This study was undertaken 1) to find out whether we can type major histocompatibility class II antigens from the paraffin-embedded series of thyroid tissue, and 2) to investigate whether HLA-DQ genes are involved in conferring a risk of Hashimoto's thyroiditis. To this end we used the polymerase chain reaction to amplify DNA from paraffin-embedded thyroid tissue blocks of histologically proven Hashimoto's disease. We used 46 specimens for HLA-DQA and 32 for DQB typing. The alleles were identified by sequence-specific oligonucleotide hybridizations. Fifty controls from the same geographic region were also typed using peripheral leukocyte DNA. HLA-DQA0301 (in linkage disequilibrium with DR4) was significantly increased (58.7% vs. 32% in controls; chi 2 = 6.73; P less than 0.01) in patients compared to controls. DQB0201 (in linkage disequilibrium with DR3) was also increased in the patient group (66% vs. 36% in controls; chi 2 = 6.63; P less than 0.01). Although DQA0301/DQB0201 heterozygotes (18.8%) were increased in patients compared to controls (6%), the difference was not significant. However, 81% of the patients (26 of 32) were DQA0301 and/or DQB0201 positive compared to 48% of controls (chi 2 5.98; P less than 0.05). We conclude that it is feasible to type HLA antigens from tissue blocks and that susceptibility to Hashimoto's disease is probably mediated through two pathways: DQA0301/DR4 and DQB0201/DR3.

Alleles↗
PubMed1992

Telephone modem access improves diabetes control in those with insulin-requiring diabetes.

OBJECTIVE: To assess whether modem access improves diabetes control in IDDM patients. RESEARCH DESIGN AND METHODS: Forty-two patients participated in the study and were followed for 12 wk. The patients were randomly divided into two groups at baseline, a modem group and a control group. There were no significant differences between HbA1c, random blood glucose, and weight between the groups at the beginning of the study. Patients were asked to perform five blood glucose determinations/day (before breakfast, before lunch, afternoon [1500], before dinner, and at bedtime) twice/week. The modem group transferred their data over the phone once/week. The control group would bring in their results on their regular visits every 6 wk. Patients in the modem group were counseled every week over the telephone after transferring results to adjust insulin and food intake if necessary. RESULTS: In the modem group, HbA1c improved from 0.106 to 0.092 (13.20%). The control group improved from 0.112 to 0.102 (8.9%). There was no significant change in weight, random blood glucose, or insulin. CONCLUSIONS: The use of telephone modem-based patient-monitoring systems in diabetes clinical research seems to stimulate the patient to keep closer control of blood glucose levels. It might be especially useful in rural settings, for which this study was designed.

Adolescent↗
PubMed1991

High rates of ras codon 61 mutation in thyroid tumors in an iodide-deficient area.

Using polymerase chain reaction and sequence-specific oligonucleotide hybridization, the frequency of three ras oncogene mutations (N-ras, Ha-ras, and K-ras) in thyroid tumors (25 adenomas, 16 follicular carcinomas, and 22 papillary carcinomas) was investigated in both iodide-deficient and iodide-sufficient areas. The ras oncogene mutation rate was significantly higher in the iodide-deficient area, being 85 versus 17% in the adenomas, and 50 versus 10% in the follicular carcinomas. No mutations were found in papillary carcinomas. The most common mutation site was Ha-ras codon 61 with Gln----Arg substitution. Two ras mutations at codon 61 (Gln----Lys in N-ras and Gln----Arg in Ha-ras) were found in a microfollicular adenoma specimen from Eastern Hungary. We conclude that dietary iodine may modulate ras oncogene mutations, and that in the iodide-deficient area, ras oncogene activation may play a more important role in the initiation and/or maintenance of follicular tumors. Additional factors are, however, necessary to initiate carcinogenesis.

Adenocarcinoma↗
PubMed1991

HLA-DR1 is associated with vitiligo.

In Eastern Hungary, vitiligo is found to be associated with HLA-DR1. When other autoimmune disorders are also present, DR3 is also increased.

Autoimmune Diseases↗
PubMed1991

Soluble interleukin-2 receptor in sera of patients with Graves' disease.

Activation of T lymphocytes has been found to be associated with an increase in soluble interleukin-2 receptor (sIL-2R) levels. The aim of this study was to investigate serum levels of sIL-2R in 20 untreated patients with Graves' disease and to relate these levels to disease activity and to TSH-receptor, anti-thyroglobulin, anti-microsomal and anti-eye muscle antibodies. sIL-2R levels were significantly increased in newly diagnosed Graves' patients compared with controls (667 +/- 270 vs 205 +/- 45 U/ml) (P less than 0.001). The sIL-2R levels were higher in patients with active infiltrative ophthalmology than in those without eye symptoms (810 +/- 313 vs 525 +/- 180 U/ml). All patients were treated with methimazole for at least 12 months. sIL-2R levels were normalized by methimazole treatment in the majority of patients without ophthalmopathy but not in those with ophthalmopathy. In five patients sIL-2R serum levels were studied after interruption of thyrostatic therapy. An increase was observed in three patients and hyperthyroidism subsequently relapsed in two of these. Furthermore, a correlation was found between soluble interleukin-2 receptor levels and TSH-receptor antibodies but not with other immune parameters examined. Serum sIL-2R represents a useful marker of immunological activity in Graves' disease.

Autoantibodies↗
PubMed1991

Soluble interleukin-2 receptor in sera of patients with Graves' disease.

Recently, in vitro production of interleukin-2 receptor induced by mitogens have been shown to be impaired in autoimmune disorders including organo-specific autoimmune diseases. The aim of this study was to investigate serum levels of soluble interleukin-2 receptor in 20 untreated patients with Graves' disease and to follow up their changes in relation to clinical picture and TSH-receptor-, anti-thyroglobulin-, anti-microsomal as well as anti-eye muscle antibodies. Soluble interleukin-2 receptor level was significantly increased in newly-diagnosed Graves' patients compared to controls (667 +/- 270 vs. 205 +/- 45 U/ml) (P less than 0.001). Among the patients sera those with active infiltrative ophthalmopathy had higher soluble interleukin-2 receptor levels than those without eye symptoms (810 +/- 313 vs. 525 +/- 180 U/ml). Soluble interleukin-2 receptor level was normalized in Methimazole-treatment-induced remission in the majority of patients except those with ophthalopathy. In five patients the soluble interleukin-2 receptor levels were studied after interruption of thyrostatic therapy; an increase was observed in three patients; thereafter hyperthyrosis relapsed in two cases. Furthermore, a correlation was found between soluble interleukin-2 receptor levels and TSH-receptor antibodies, however, the association with other immune parameters examined was not significant. In conclusion, an enhanced level of soluble interleukin-2 receptor was detected in patients with untreated Graves' disease. This finding might play a significant role in regulation of impaired cell-mediated immune mechanism and has a prognostic value for relapse of autoreactive processes.

Adult↗
PubMed1990

Immunocytochemical localization of bovine thyrotropin and thyroid auto-antibodies in porcine thyrocytes.

Interactions of receptor-bound bovine thyrotropin (bTSH) and immunoglobulins G from sera of patients with Graves' (G-IgG) or Hashimoto's (H-IgG) disease with porcine thyrocytes were studied by immunocytochemistry. Porcine thyroid fragments were fixed and prepared for immunoreaction or enzymatically dissociated with collagenase and dispase II. The dispersed cells were cultured in primary monolayer in a hormone-free medium or in a medium with bTSH (150 micrograms/ml) for 7 days. After immunostaining the thyrocytes in fragments and monolayers were stained with periodic acid Schiff (PAS) or with PAS and haemalum. Cultivation of the isolated thyrocytes in bTSH-enriched medium leads to a monolayer with globular aggregates, i.e., reconstructed three-dimensional follicles. Follicular cells in these monolayers and in fragments give a weak to moderate immunoreaction to anti-bTSH and a strong reaction to G-IgG and H-IgG (vs. control IgG). Precipitate is found particularly in the perinuclear area and to a lesser degree throughout the cytoplasm. Cells cultured in the absence of bTSH show minimal immunoreaction to anti-bTSH, but moderate reaction to G-IgG and H-IgG. Preincubation with bTSH leads to a strong reduction of immunoreaction to G-IgG but does not affect reaction to H-IgG. Morphological results indicate that G-IgG and H-IgG interact with the same cellular sites as bTSH. Hashimoto's disease antibodies bind to a determinant on the TSH receptor separate from the one on which TSH and Graves' IgG bind.

Animals↗
PubMed1990

Cytogenetic analyses of three papillary carcinomas and a follicular adenoma of the thyroid.

Cytogenetic data of three papillary carcinomas and a follicular adenoma using direct preparations or cell cultures or both after 7 to 60 days in vitro are presented. Although karyotype of the follicular adenoma proved completely normal, in each of the three papillary carcinomas a modal chromosome number in the diploid range and a deleted 11q were observed. In case 1 the del(11)(q23) was associated with rearrangement of chromosome 1 and other marker chromosomes. Our results suggest that 11q deletion may be specific for papillary carcinoma of the thyroid.

Adenoma↗
PubMed1990

Cellular and humoral autoimmune responses against human eye muscle membrane antigen in Graves' disease.

75 patients with Graves' disease (54 with ophthalmopathy) were investigated using the tests of leucocyte adherence inhibition and immune adsorption with 125I-labelled Staphylococcus Protein A, against human eye muscle "crude" membrane antigen. The results of positive leucocyte adherence inhibition (10 out of 26 vs. 1 out of 28, P less than 0.05) and anti-human eye muscle membrane antibody index (mean +/- S.D.) (1.89 +/- 1.20 vs. 0.84 +/- 0.38, P less than 0.001) showed a correlation with the patients with clinically active eye disease and the HLA-B8 antigen in Graves' ophthalmopathy (P less than 0.01). Positive leucocyte adherence inhibition was observed in 9 out of 21 cases of Graves' disease without ophthalmopathy, but its prognostic relevance has to be confirmed in the development of ophthalmopathy.

Antibody Formation↗
PubMed1989

The cardinal manifestations of Bardet-Biedl syndrome, a form of Laurence-Moon-Biedl syndrome.

To determine the interfamilial and intrafamilial variation in the expression of the Bardet-Biedl syndrome (a form of Laurence-Moon-Biedl syndrome), we looked for the five recognized features of the disorder (retinal dystrophy, obesity, polydactyly, mental retardation, and hypogonadism), plus possible renal manifestations, in some or all of 32 patients with this disorder. All 28 patients examined had severe retinal dystrophy, but only 2 had typical retinitis pigmentosa. Polydactyly was present in 18 of 31 patients, but syndactyly, brachydactyly, or both were present in all. Obesity was present in all but 1 of 25 patients. Only 13 of 32 patients were considered mentally retarded. Scores on verbal subtests of intelligence were usually lower than scores on performance tasks. Seven of eight men had small testes and genitalia, which was not due to hypogonadotropism. All 12 women studied had menstrual irregularities, and 3 had low serum estrogen levels (1 of these had hypogonadotropism, and 2 had primary gonadal failure). The remaining women who were of reproductive age had endocrinologic evidence of reproductive dysfunction. Diabetes mellitus was present in 9 of 20 patients. Renal structural or functional abnormalities were universal (n = 21), and three patients had end-stage renal failure. We conclude that the characteristic features of Bardet-Biedl syndrome are severe retinal dystrophy, dysmorphic extremities, obesity, renal abnormalities, and (in male patients only) hypogenitalism. Mental retardation, polydactyly, and hypogonadism in female patients are not necessarily present.

Female↗
PubMed1989

Immunogenetic and immunologic studies of differentiated thyroid cancer.

The authors have studied in detail human leukocyte antigen (HLA) association in 87 Hungarian patients with thyroid epithelial carcinoma. The authors also examined in a small group of patients, five parameters of cell-mediated immunity and related them to HLA as well as to lymphocytic infiltration of the tumor/normal tissue interface. HLA-DR1 was significantly associated with thyroid carcinoma; the strongest association was in patients with follicular histologic features and DR1 homozygotes were not at greater risk for thyroid cancer. The HLA-DR3 was nonsignificantly increased in patients with papillary or mixed histologic features. The HLA-DR1, 3 heterozygotes were highly associated with follicular carcinoma, carried no risk for papillary carcinoma, and an intermediate risk for tumors with mixed histologic features. Because of the small proportion of DR1, 3 heterozygotes in the follicular and mixed histologic group, its predictive value at the population level was low. Better predictive potential was shown for the phenotype DR1 and/or DR3. Neither metastatic disease nor age at diagnosis (less than 45 years) could be related to HLA phenotypes. Patients in all histologic variants showed some measure of cell-mediated immunity compared to controls. Patients with papillary carcinoma showed an overall better response than those with tumors with follicular or mixed histology. The HLA-DR could not be related to cell-mediated immune response. Patients with papillary carcinoma with a good cell-mediated immune response occurred with much lower infiltration of the tumor boundary with lymphocyte whereas the follicular carcinoma less cell-mediated immunity was associated with dense lymphocytic infiltration, suggesting the biological relevance of lymphocytic infiltration may be different for the two histologic variants.

Adenocarcinoma↗
PubMed1989

Cytotoxic endothelial cell antibodies in mixed connective tissue disease.

We examined the presence of anti-endothelial cell antibodies in the sera of 44 patients with mixed connective tissue disease (MCTD). Warm antibodies against endothelial cells were found in 45.4% of patients; the presence of these antibodies was positively correlated with anti-monocyte antibodies (P less than 0.01) but not with anti-lymphocytic antibodies. Strong correlations were found between the presence of these antibodies and abnormalities of pulmonary ventilatory capacity, neurophysiologic and myocardial function. Anti-endothelial antibodies were related to the high rate of spontaneous abortion noted in female MCTD patients. The identification of the antigen identified by MCTD sera in endothelial cells would help in understanding disease manifestations.

Adult↗
PubMed1989

B lymphocyte subsets in Hashimoto's thyroiditis.

Two B lymphocyte subsets are identified on the basis of possession or lack of a surface molecule, CD5. The CD5+ B lymphocytes synthesize autoantibodies and in the process rearrange proximal variables of immunoglobulin genes. We have here studied the proportion and absolute counts of CD5+ B lymphocytes in the peripheral blood of 31 patients with Hashimoto's thyroiditis and related the findings to their HLA phenotypes and clinical features. Although the percentage and absolute number of surface immunoglobulin-positive (B) lymphocytes was comparable in patients to those in twenty controls, % CD5+ was significantly higher in the patient group (38.1 +/- 11.6 [+/- S.D.] vs. 27.9 +/- 10.1, p = 0.009). The absolute CD5+ cells (microliters) were also higher in patients with Hashimoto's thyroiditis (77.90 +/- 37.50 vs. 55.1 +/- 29.8, p = 0.020). The proportion of CD5+ cells was even higher in HLA-DR3 positive patients (43.1% +/- 7.2, n = 13) compared to six DR3+ controls (26.17% +/- 9.7, p = 0.0005). The difference between DR3- patients and controls was not significant (28.6% +/- 10.5 vs. 34.4% +/- 13.0). As the CD5 molecule may be induced on activated B lymphocytes, this study suggests that Hashimoto's thyroiditis is associated with an increase of activated B lymphocytes engaged in autoantibody synthesis. This defect is particularly obvious in DR3+ patients.

Antigens, Differentiation↗