Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An autoimmune disease can be the cause of thyroid disfunction. Determination of autoantibodies titers is the best way of demonstrating its existence. We studied 172 thyroid patients (146 females, 26 males) with ages ranging from 15 to 81 years. Thyroid microsomal autoantibodies (TMA) were detected by a modified agglutination test (SERA-TEK kit, Ames Div); a dilution greater than or equal to 1/1600 was considered as diagnostic of autoimmune disease. Patients were classified according to morphological and functional status in 3 groups: GI = non toxic goiter, n = 98 (71 diffuse, 20 multi and 7 uninodular); GII = toxic goiter, n = 62 (52 diffuse, 4 multi, 2 uninodular and 4 subacute thyroiditis); G III = hypothyroidism, n = 12 (5 primary hypothyroidism and 7 chronic thyroiditis). A control group of 30 normal individuals, ages ranging from 19 to 85 years was also studied. Diagnostic titers of TMA were found in 30.8% of group I, 88.5% of group II, 91.6% of group III and only in 6.6% of controls. The high incidence of positive TMA in toxic diffuse goiter (96.1%) as well as in hypothyroid patients was expected since these are typical examples of thyroid autoimmune disease. In the non toxic goiter group, positive TMA were present in 50% of multinodular, 28% of uninodular and 25% of diffuse goiters and the incidence of positive TMA varied according to age, being higher over the age of 40 years and lower under the age of 20 years. We postulate that this unexpected high incidence of positive TMA in non toxic goiter is due to amelioration of chronic iodine deficiency inducing the expression of latent autoimmune disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Thyroid microsomal autoantibodies in thyroid disease: their value as an antigenic marker]. 251 89

Thyroid hormone dependent transcription stimulatory and inhibitory elements exist at the 5'-end of the rat GH (rGH) gene (TSE and TIE, respectively). In this study, the location of the sequences essential for TSE activity was examined using stably transfected GC cells. Because the TIE may influence TSE activity, we investigated TSE activity both on the rGH promoter, in the presence of the TIE, and on the viral thymidine kinase promoter, with the TIE deleted. The results of these studies indicate that the minimum sequences essential for TSE activity exist between positions -194 and -169 of the rGH gene.
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PMID:Sequences essential for activity of the thyroid hormone responsive transcription stimulatory element of the rat growth hormone gene. 284 60

Recently identified mutations affecting different domains of the RET proto-oncogene are associated with Multiple Endocrine Neoplasia type 2A (MEN 2A) and type 2B (MEN 2B), familial and sporadic Medullary Thyroid Carcinomas (MTC) and Hirschsprung disease (HSCR). In order to facilitate the screening for RET mutations, and to study possible genotype-phenotype correlations, we established exon-intron junctions and extended the intronic sequences flanking the 20 exons of this gene. This made it possible to design primers and to develop PCR conditions useful for SSCP analysis of the whole RET coding sequence. Nine conformational variants were observed which after sequencing turned out to be 8 silent mutations and a conservative amino acid substitution. Restriction analysis performed on DNA samples from unrelated controls confirmed the polymorphic nature of six of these nucleotide changes and made it possible to estimate the frequency of the corresponding alleles.
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PMID:DNA polymorphisms and conditions for SSCP analysis of the 20 exons of the ret proto-oncogene. 770 Jun 53

Medullary thyroid carcinoma (MTC) is a malignancy of the thyroid C-cells that comprises 5-10% of all thyroid cancers. MTC occurs in both sporadic and familial forms, the latter making up 25% of all MTCs and being comprised of three distinct syndromes--multiple endocrine neoplasia type 2A (MEN 2A), multiple endocrine neoplasia type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC). To date, screening for MTC has been performed using the pentagastrin stimulation test, which is a provocative test for calcitonin release. Germline mutations in the RET protooncogene have been identified in families manifesting these syndromes and genetic screening of individuals at risk of one of these syndromes has become integral to their clinical management. The majority of the mutations associated with MEN 2A and FMTC are tightly clustered in a cysteine-rich region of the RET receptor. A single mutation associated with MEN 2B is in the the tyrosine kinase domain of the RET receptor. Somatic mutations have been identified in the tumor tissue of individuals with sporadic MTC and may prove to be helpful markers in discerning the hereditary or sporadic nature of the MTC. There is general agreement that the primary operation for MTC should include total thyroidectomy and central neck lymph node clearance. The role of microdissection for recurrent disease awaits longitudinal evaluation. External radiotherapy, radionuclide therapy, and chemotherapy may have a role in palliation, but have not been proven to have a curative value. Prognostic factors are discussed.
Thyroid 1995 Oct
PMID:Medullary thyroid carcinoma: recent advances and management update. 856 82

RET germline mutations were found to predispose to the development of three variants of multiple endocrine neoplasia type 2, MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC). We have screened for RET mutations at exons 10, 11, 13, and 16 in leukocyte DNA extracted from 37 individuals, and have identified RET germline mutations in 12 affected individuals from 9 unrelated families. No RET germline mutation was found in 19 individuals with apparent sporadic diseases. We have also screened for RET mutations at exons 10, 11, and 16 in tumor DNA extracted from 13 freshly frozen medullary thyroid carcinomas (MTC). RET mutation was detected in every tumor, either inherited or sporadic, indicating that RET plays an important role in the development of both inherited and sporadic MTC. We initially screened for RET mutations by direct DNA sequencing of the genomic PCR products amplified from patients' leukocyte or tumor DNA. Recently, we utilized the "Cold SSCP" method, nonradioactive single-stranded conformation polymorphism analysis, to screen for RET mutations and have identified a novel mutation, a 6-bp deletion preceding the cysteine-634, in a sporadic MTC.
Thyroid 1996 Apr
PMID:RET mutation screening in MEN2 patients and discovery of a novel mutation in a sporadic medullary thyroid carcinoma. 873 82

Direct DNA analysis permits accurate identification of gene carriers in kindred members with multiple endocrine neoplasia type 2A (MEN 2A). The aim of this study was to assess the specificity of basal and pentagastrin stimulated calcitonin levels in 3 family members with MEN 2A. For this purpose 53 members of 3 consecutive families with MEN 2A were evaluated in a university medical center. Serum calcitonin, basal and stimulated, was determined by a commercial RIA. RET protooncogene analysis was carried out by automatic DNA sequencing and adequate digestion of PCR amplified products for exons 10 and 11. Two distinct mutations in the RET protooncogene were identified. A T-->A transition at position 1783 (codon 618) in exon 10 was detected in one family, and a G-->A replacement at position 1832 (codon 634) in exon 11 in the others. In non-gene carriers we obtained 6.6% of false-positive results for basal calcitonin and 15.4% for the pentagastrin provocative test. We conclude that the specificity of basal and pentagastrin-stimulated calcitonin is rather limited and RET protooncogene analysis must be the first line screening procedure in order to identify gene carriers.
Thyroid 1997 Feb
PMID:False-positive results of basal and pentagastrin-stimulated calcitonin in non-gene carriers of multiple endocrine neoplasia type 2A. 908 71

Thyroid carcinomas of an additional series of 34 children exposed to radioactive fall-out after the Chernobyl reactor accident were analysed for mutations in the H-, K- and N-RAS and the p53 gene. Allele-specific oligonucleotide hybridization, single-strand conformation polymorphism (SSCP) and direct sequencing did not disclose mutations in codons 12, 13 and 61 of RAS genes nor mutations in exons 5, 7 and 8 of p53. Considering the recently reported high prevalence of RET rearrangements of the PTC3 type in childhood tumours after Chernobyl (Klugbauer et al, 1995, Oncogene 11: 2459-2467), it follows that RET rearrangements are the most relevant molecular aberration in these radiation-induced tumours. RAS or p53 mutations do not play a role in childhood thyroid carcinogenesis after Chernobyl.
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PMID:Absence of RAS and p53 mutations in thyroid carcinomas of children after Chernobyl in contrast to adult thyroid tumours. 952 40

An epidermal growth factor (EGF)-dextran-boron conjugate for targeting against EGF receptor-rich tumours was investigated regarding uptake and distribution in vivo. EGF served as the tumour-seeking part and dextran was the carrier for the potentially toxic boron. Nude mice carrying subcutaneous tumours on the flanks were injected with conjugate either i.v. or intratumorally. The xenografts were from Chinese hamster ovary cells transfected with the gene for the human EGF-receptor (CHO-EGFR), and these cells expressed the EGFR. Non-transfected cells without EGF-receptors (CHO) were used as controls. No accumulations in tumours could be observed following the i.v. injections but there were, in both tumour types, high accumulations in the liver. Following intratumoral injections the accumulations were higher in the CHO-EGFR tumours than in the CHO tumours. The tumour over blood and liver ratios were also higher for the CHO-EGFR tumours than for the CHO tumours. Thyroid accumulations after the intratumoral injections indicate different degradation patterns of the conjugate in CHO-EGFR animals than in CHO animals. In conclusion, after intratumoral injections the conjugate showed receptor-dependent binding to EGFR-rich tumours, and the tumour-to-blood and tumour-to-liver ratios were promising.
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PMID:Uptake of a boronated epidermal growth factor-dextran conjugate in CHO xenografts with and without human EGF-receptor expression. 962 68

The RET proto-oncogene encodes two isoforms of a receptor tyrosine kinase which plays a role in neural crest and kidney development. Ret ligands have been recently identified as the neuron survival factor GDNF (Glial-Derived Neurotrophic Factor) and Neurturin. Somatic rearrangements of RET, designated RET/PTCs, have been frequently detected in papillary thyroid carcinomas. In addition, distinct germ-line mutations of RET gene have been associated with the inherited cancer syndromes MEN (Multiple Endocrine Neoplasia) 2A, 2B and FMTC (Familial Medullar Thyroid Carcinomas) as well as with the congenital megacolon or Hirschsprung's disease, thus enlightening a significant role of this receptor gene in diverse human pathologic conditions. In this study, by performing classical inhibition experiments using synthetic phosphopeptides and by site-directed mutagenesis of the putative docking site, we have determined that for Grb2 the latter is provided by the tyrosine 620 of Ret/ptc2 long isoform (corresponding to Tyr 1096 on proto-Ret). However, in intact cells, the interaction of Grb2 with the two short and long Ret isoforms expressed separately is of similar strength, thus suggesting that Ret short isoform interaction with Grb2 could be mediated not only by Shc but also by a molecule that binds preferentially to this isoform. This possibility is supported by the evidence that the mutant Ret/ptc2Y620F long isoform displays a weak coimmunoprecipitation with Grb2 and that this mutant, lacking the docking site for Grb2 but owing all the others phosphotyrosines, surprisingly displays a reduced transforming activity compared to that of the two WTs oncogenes. We thus conclude that in intact cells both Ret isoforms bind to Grb2, although with different modalities. In addition, the present results are in agreement with the possibility that different signal transduction pathways are associated with the two isoforms of Ret.
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PMID:Grb2 binding to the different isoforms of Ret tyrosine kinase. 976 18

Multiple endocrine neoplasia type 2 (MEN 2) is a rare syndrome of medullary thyroid carcinoma (MTC) with pheochromocytoma and/or primary hyperparathyroidism (PHP), usually due to multigland hyperplasia. MEN 2 is associated with several RET protooncogene mutations. A 61-year-old woman with a family history of RET-positive MTC presented with a solitary thyroid nodule. Fine-needle aspiration biopsy was suspicious for neoplasm. Biochemical studies revealed basal hypercalcitoninemia (116 pg/mL [normal <26]) and PHP (serum calcium, 10.9 mg/dL; intact PTH, 113.2 pg/mL [10.0-65.0]). Pheochromocytoma screening was negative. A provisional diagnosis of MEN 2 was made, but at surgery, a single parathyroid adenoma was resected and frozen sections of several lymph nodes revealed papillary thyroid carcinoma (PTC). A total thyroidectomy was performed. Final histological diagnosis was PTC and parathyroid adenoma with no evidence of MTC. Postoperatively, RET mutation testing was positive. The basal calcitonin (CT) fell to 25 pg/mL, but peaked at 935 (normal <105) after pentagastrin infusion, consistent with occult MTC. After radioiodine ablation, CT decreased further. Octreotide scanning was negative. Faced with PHP, a thyroid nodule, and a family history of MTC, clinicians tend to diagnose MEN 2. This patient had a single parathyroid adenoma and nonmedullary thyroid cancer, which the literature actually suggests to be an association more frequent than MEN 2. Yet, there remains compelling data in favor of occult MTC, leaving open the possibility of an MEN 2 variant with the rare association of PTC.
Thyroid 1998 Sep
PMID:Papillary thyroid carcinoma, parathyroid adenoma, and unexplained hypercalcitoninemia: an unusual presentation of multiple endocrine neoplasia type 2A? 977 49


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