Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039483 (giant cell arteritis)
 3,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polymyalgia rheumatica (PMR) is a disease of unknown etiology characterized by severe myalgia and stiffness at shoulder girdle and pelvic girdle muscles and by normal serum creatine kinase levels. Marked elevation of erythrocyte sedimentation rate, acute onset within two weeks, and appearance in the aged are also additional characteristics of PMR. Ten to 50% of PMR patients have a concomitant temporal arteritis (TA)(giant cell arteritis). For the differential diagnoses of PMR, rheumatoid arthritis, polymyositis, fibromyalgia, malignancies, infections and depression should be considered. PMR without TA is treatable successfully with small amount of steroids (15-20 mg/day of prednisolone). For the PMR patients with TA should be treated with large amount of steroids (40-60 mg/day of prednisolone) or steroid pulse therapy.
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PMID:[Polymyalgia rheumatica]. 1007 7

ErbB-2 is overexpressed in several human cancers and conveys a transforming activity that is dependent on tyrosine kinase activity. Antibodies and T cells to ErbB-2 have been isolated from cancer patients, indicating ErbB-2 as a potential target of active vaccination. In this study, 3 mutant ErbB-2 DNA constructs encoding full-length, ErbB-2 proteins were tested as tumor vaccines. To eliminate tyrosine kinase activity, the ATP binding lysine residue 753 was substituted with alanine by replacing codon AAA with GCA in mutant ErbB-2A. To direct recombinant ErbB-2 to the cytoplasm where major histocompatibility complex (MHC) I peptide processing takes place, the endoplasmic reticulum (ER) signal sequence was deleted in cyt ErbB-2. The third construct cyt ErbB-2A contained cytoplasmic ErbB-2 with the K to A mutation. Expression of recombinant proteins was measured by flow cytometry in transfected murine mammary tumor cell line D2F2. Transmembrane ErbB-2 and ErbB-2A were readily detected. Cytoplasmic ErbB-2 and ErbB-2A were detected only after the transfected cells were incubated overnight with a proteasome inhibitor, indicating prompt degradation upon synthesis. ErbB-2 autophosphorylation was eliminated by the K to A mutation as demonstrated by Western blot analysis. Growth of ErbB-2-positive tumor in BALB/c mice was inhibited after vaccination with ErbB-2 or ErbB-2A, but not with cyt ErbB-2 or cyt ErbB-2A. ErbB-2A that is free of tyrosine kinase activity is a potential candidate for anticancer vaccination. The 3 mutant constructs should be useful tools to delineate the role of individual immune effector cell in ErbB-2-specific antitumor immunity and to develop strategies for enhancing such immunity.
Int J Cancer 1999 May 31
PMID:Protection against mammary tumor growth by vaccination with full-length, modified human ErbB-2 DNA. 1032 28

Mxi1 is thought to negatively regulate Myc function and may therefore be a potential tumor suppressor gene. Little effort has yet been made to find alterations involving this gene in human solid tumors. We screened 31 human gastric cancers, 7 esophageal cancers, 85 bone and soft tissue tumors of various types, including 4 neurofibrosarcomas. We also examined 29 human tumor cell lines consisting of 12 esophageal cancers, 7 glioma/glioblastomas and 10 others for Mxi1 mutations in exons 1, 2, 4 (HLH domain), 5 and 6. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and subsequent sequencing revealed three distinct polymorphisms in the intron-exon boundary upstream from exon 6. We discovered a missense mutation, GCA to GTA (Ala 54 Val), in exon 2 in a neurofibrosarcoma patient (case 1), two missense mutations, AAA to CAA (Lys 118 Gln) and GAA to GGA (Glu 154 Gly) in exon 5 of another neurofibrosarcoma patient (case 2), and 3 amino acid substitutions, GTG to GCG (Val 179 Ala), GTT to GCT (Val 181 Ala) and TTC to CTC (Phe 186 Leu), in a third neurofibrosarcoma patient (case 3). In case 3, loss of heterozygosity was also demonstrated by informative (TTC)3/(TTC)2 polymorphism. Our data demonstrate that mutations occur in the Mxi1 gene in neurofibrosarcoma. Missense mutations in the functional domain of Mxi1 in these cases may be involved in the pathogenesis of neurofibrosarcoma.
Jpn J Cancer Res 1999 Jul
PMID:Mxi1 mutations in human neurofibrosarcomas. 1047 Feb 86

Within the context of continuing interest in occupational hygiene of hospitals as workplaces, the authors report the results of a preliminary study on surface contamination by certain antineoplastic drugs (ANDs), recently performed in eight cancer departments of two large general hospitals in Milan, Italy. Since reliable quantitative information on the exposure levels to individual drugs is mandatory to establish a strong interpretative framework for correctly assessing the health risks associated with manipulation of ANDs and rationally advise intervention priorities for exposure abatement, two automated analytical methods were set up using reverse-phase high-performance liquid chromatography for the measurement of contamination by 1) methotrexate (MTX) and 2) the three most important nucleoside analogue antineoplastic drugs (5-fluorouracil 5FU, Cytarabin CYA, Gemcytabin GCA) on surfaces such as those of preparation hoods and work-benches in the pharmacies of cancer wards. The methods are characterized by short analysis time (7 min) under isocratic conditions, by the use of a mobile phase with a minimal content of organic solvent and by high sensitivity, adequate to detect surface contamination in the 5-10 micrograms/m2 range. To exemplify the performance of the analytical methods in the assessment of contamination levels from the target analyte ANDs, data are reported on the contamination levels measured on various surfaces (such as on handles, floor surfaces and window panes, even far from the preparation hood). Analyte concentrations corresponding to 0.8-1.5 micrograms of 5FU were measured on telephones, 0.85-28 micrograms/m2 of CYA were measured on tables, 1.2-1150 micrograms/m2 of GCA on furniture and floors. Spillage fractions between 1-5% of the used ANDs (daily use 5FU 7-13 g; CYA 0.1-7.1 g; GCA 0.2-5 g) were measured on the disposable polythene-backed paper cover sheet of the preparation hood.
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PMID:Measurement of surface contamination by certain antineoplastic drugs using high-performance liquid chromatography: applications in occupational hygiene investigations in hospital environments. 1052 8

The erythrocyte sedimentation rate (ESR) determination is a commonly performed laboratory test with a time-honored role. However, the usefulness of this test has decreased as new methods of evaluating disease have been developed. The test remains helpful in the specific diagnosis of a few conditions, including temporal arteritis, polymyalgia rheumatica and, possibly, rheumatoid arthritis. It is useful in monitoring these conditions and may predict relapse in patients with Hodgkin's disease. Use of the ESR as a screening test to identify patients who have serious disease is not supported by the literature. Some studies suggest that the test may be useful as a "sickness index" in the elderly or as a screening tool for a few specific infections in certain settings. An extreme elevation of the ESR is strongly associated with serious underlying disease, most often infection, collagen vascular disease or metastatic malignancy. When an increased rate is encountered with no obvious clinical explanation, the physician should repeat the test after an appropriate interval rather than pursue an exhaustive search for occult disease.
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PMID:Clinical utility of the erythrocyte sedimentation rate. 1052 88

We describe a 34-year-old woman with periarteritis nodosa (PAN) presenting as a breast lesion. Localized involvement of the breast is an unusual manifestation of PAN. To date, 10 cases have been reported: all were in women with an age range of 45-78 years (mean 63). In most cases, breast lesions were an isolated finding, and the prognosis was favourable, setting them apart from the more common form of systemic PAN. The case presented is unusual in that vasculitis developed in the postpartum period, and was associated with cutaneous PAN-like lesions elsewhere on the body, and digital artery occlusion. The most important differential diagnoses of PAN of the breast are infectious mastitis, mammary malignancy and other forms of idiopathic vasculitides of the breast, e.g. giant cell arteritis and Wegener granulomatosis.
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PMID:Periarteritis nodosa presenting as a breast lesion: report of a case and review of the literature. 1060 64

We examined cDNAs of the catalytic subunit of DNA polymerase alpha (185 kDa), the 70 kDa subunit of replication protein A (single-stranded DNA-binding protein) and the 140 kDa subunit of replication factor C for mutations. Surgical specimens from 12 patients with sporadic colon cancer and normal mucosae from the same patients were investigated. In addition, we analyzed 3 human colon cancer cell lines that exhibited defects in mismatch repair (DLD-1, HCT116, SW48) and 3 colon cancer cell lines without such a defect (HT29, SW480 and SW620). For detection of mutations, we used reverse transcription of mRNA, amplification of cDNAs by PCR, analysis of single-strand conformation polymorphism and DNA sequencing. Eleven colon cancers and 6 colon cancer cell lines were analyzed for DNA polymerase alpha. Only 2 silent point mutations were detected, in 1 colon carcinoma and in cell line HCT116. Two sequence alterations of the 70 kDa subunit of replication factor A were identified in 15 specimens (9 colon carcinomas and 6 cell lines). Colon carcinomas from 2 patients (CC5MA and CC25HN) exhibited an ACA-->GCA transition in codon 351, which caused a Thr-->Ala exchange. In carcinomas CC5MA and CC8MA, a TCC-->TCT (Ser-->Ser) transition in codon 352 was observed. The deviations in codons 351 and 352 occurred in both cancer tissues and normal mucosae, suggesting a genetic polymorphism. No mutation was found in the 140 kDa subunit of replication factor C from 16 specimens (10 tumors and 6 cell lines). Point mutations were identified in the p53 tumor-suppressor gene in 4 of the 6 colon cancer cell lines and 3 of the 8 carcinoma specimens. We did not find tumor-associated DNA sequence alterations that resulted in amino acid changes in the DNA replication genes analyzed. We infer that the scarcity of mutations found is due to stringent selection, eliminating functionally impaired replication proteins.
Int J Cancer 2000 May 01
PMID:Mutation analysis of replicative genes encoding the large subunits of DNA polymerase alpha and replication factors A and C in human sporadic colorectal cancers. 1076 Aug 17

p27(Kip1) is an inhibitor of cyclin-dependent kinase. It has been reported that reduced p27(Kip1) expression is present in human hepatocellular carcinoma. To determine the role of p27(Kip1) in hepatocarcinogenesis, 46 cases with hepatocellular carcinomas were studied. p27(Kip1) mutation was first screened by single strand conformation polymorphism, and direct DNA sequencing was then performed on those cases with mobility shifts. Two polymorphism sites were found. One is a previously described polymorphism at codon 109 (GTC-->GGC) which was found in two cases. The second polymorphism was identified at codon 55 (GCG-->GCA) in six of the 46 cases. However, the polymorphism at codon 55 was also present in seven of 93 healthy controls (7.5%), indicating that it is not associated with a predisposition for development of hepatocellular carcinoma (Fisher's exact test, 0.05). These results show that p27(Kip1) mutation is not a frequent event in human hepatocellular carcinoma, and suggest that it may be inactivated predominantly by transcriptional and/or posttranscriptional regulation rather than genomic aberrations.
Cancer Lett 2000 May 29
PMID:Mutational analysis of the p27(kip1) gene in hepatocellular carcinoma. 1077 46

Peutz-Jeghers syndrome (PJS) is an autosomal dominantly inherited disease characterized by hamartomatous gastrointestinal polyps and mucocutaneous pigmentation, with an increased risk for various neoplasms, including gastrointestinal cancer. Recently, the PJS gene encoding the serine/threonine kinase STK11 (also named LKB1) was mapped to chromosome 19p13.3, and germline mutations were identified in PJS patients. We screened a total of ten Korean PJS patients (nine sporadic cases and one familial case including two patients) to investigate the germline mutations of the STK11 gene. By polymerase chain reaction-single-strand conformation polymorphism and DNA sequencing analysis, three kinds of mis-sense mutation and a frame-shift mutation were identified: codon 232 (TCC to CCC) in exon 5, codon 256 (GAA to GCA) in exon 6, codon 324 (CCG to CTG) in exon 8, and a guanine insertion at codon 342 resulting in a premature stop codon in exon 8. These mis-sense variants were not detected in 100 control DNA samples. Furthermore, we found an intronic mutation at the dinucleotide sequence of a splice-acceptor site: a one base substitution from AG to CG in intron 1, which may cause aberrant splicing. Most reported germline mutations of the STK11 gene in PJS patients were frame-shift or non-sense mutations resulting in truncated proteins. Together, these findings indicate that germline mis-sense mutations of the STK11 gene are found in PJS patients in addition to truncating mutations. The effects of these mutations on protein function require further examination. In summary, we found germline mutations of the STK11 gene in five out of ten Korean PJS patients.
Br J Cancer 2000 Apr
PMID:Germline mutations of the STK11 gene in Korean Peutz-Jeghers syndrome patients. 1078 May 18

Polymyalgia rheumatica as well as Horton's disease (arteriitis temporalis) are often diagnosed by exclusion. When either disease is suspected because of certain findings a therapy with glucocorticoids is usually started and initial therapeutic success is commonly seen as indirect proof of diagnosis. Clinical experience, however, shows that both diagnoses may conceal a malignancy. Based on this experience the cases of three patients are reported who's clinical and laboratory findings suggested first manifestations of polymyalgia rheumatica or Horton's disease respectively. During treatment, however, the true underlying disease was revealed in two of the cases. Only in one patient was the diagnosis polymyalgia correct, in the second patient a bronchial carcinoma was found, in the third a carcinoma of the breast with bone marrow carcinosis. All three patients have been presented to physicians participating in a meeting of general medicine in 1999. Before disclosure of the final diagnoses assumptions of the physicians about the initial diagnosis were analysed. The same procedure was used with last year medical students. Physicians had more correct diagnoses (19% had all three correct) than students (only 2.8%). This shows on one hand a marked general diagnostic insecurity concerning the diagnoses polymyalgia and Horton's disease on the other hand it demonstrates the advantage of medical experience gained during practice.
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PMID:[Pitfalls in diagnosis of polymyalgia rheumatica/temporal arteritis]. 1086 11


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