Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to characterise natural cell-mediated cytotoxicity against COS-7 cells transfected with potentially oncogenic HPV-8 L1 DNA sequences cloned in sense and antisense orientation and to evaluate their lysis by peripheral blood lymphocytes (PBL) from patients with epidermodysplasia verruciformis (EV), a rare disease associated with life-long infection by specific HPV types. COS-7 cells were transfected with HPV-8 Hinc II restriction fragment (nucleotide positions 5434-7654) cloned in sense (COS-L1S) and antisense (COS-L1A) orientation into pCB6 expression vector. Cytotoxic activity of isolated PBL against COS cell lines as well as K562 erythroleukaemic cells was evaluated by 51Cr-release assay. We found that lymphocytes responsible for natural lysis of COS and K562 cells are CD3-negative CD56-positive natural killer (NK) cells. Analysis of NK cell cytotoxic activity against different COS cell lines has revealed that lymphocytes from healthy subjects killed COS-L1S cells significantly more efficiently than wild COS-7 and COS-L1A cells. Significantly more efficient lysis of COS-L1S cells was also observed in EV patients. Thus, expression of HPV L1 renders target cells more susceptible to NK-mediated cytotoxicity that may enable more effective elimination of transformed cells.
Int J Mol Med 2004 Jan
PMID:Natural cell-mediated cytotoxicity of peripheral blood lymphocytes against target cells transfected with epidermodysplasia verruciformis-specific human papillomavirus type 8 L1 DNA sequences. 1465 93

Erdheim-Chester disease (ECD) is a disseminated xanthogranulomatous infiltrative disease of unknown etiology due to infiltration of different organs and bones by foamy histiocytes. A 37-year-old male with cerebral and periorbital lesions was diagnosed with this rare disease and was evaluated with magnetic resonance imaging (MRI) and 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) with positron emission tomography/computed tomography (PET/CT) imaging at baseline and following therapy. FDG-PET imaging allowed accurate evaluation of the extent of the disease at baseline, as well as assessment of response to therapy.
Mol Imaging Biol
PMID:Positron emission tomography/computed tomography of a rare xanthogranulomatous process: Erdheim-Chester disease. 1501 30

Disorders resulting from inborn errors of metabolism (IEM) affect very small numbers of individuals. The entire population, however, of patients suffering the results of inherited metabolic disorders is large, and has been of increasing concern to patient groups and health care professionals in the United States as well as other countries throughout the world. The 1983 US Orphan Drug Act (ODA) serves to facilitate the development of drugs to treat rare diseases by providing several economic incentives. The sponsor of a product designated as an orphan by the Food & Drugs Administration (FDA) Office of Orphan Products Development (OPD) qualifies for tax credits on clinical trial expenses, the award of grant funding by FDA, through the OPD, and 7 years of marketing exclusivity for a designated drug, or biological product that receives FDA market approval. Orphan drug legislation in the US has benefited victims of IEM by encouraging development of drugs for metabolic deficiencies affecting populations that otherwise would be ignored. America's solution to the orphan drug problem has had worldwide impact. The success of this legislation was a factor leading to the 1993 orphan drug law in Japan; the 1997 implementation of a process whereby most FDA-approved orphan drugs and biological products will be similarly approved in Australia; and, in 1999, regulation on orphan medicinal products in the European Union (EU). Today, international support for rare disease research is providing stimulus and motivation to overcome the financial barriers and encourage development of treatment for very rare diseases throughout the world.
Mol Genet Metab 2004 Apr
PMID:Developing treatments for inborn errors: incentives available to the clinician. 1505 Sep 76

Beta-thalassemia (beta-thal) is present in 59% and 75% of patients with abnormal hemoglobin disorders in northwestern and central Mexico, respectively. In our Research Center, up until 1997, we reported the presence of 13 beta-thal alleles in 26 unrelated chromosomes (-28A>C; -87C>T; MET1VAL; IVS1, G>A, +1; IVS1, G>A, +5; IVS1, G>C, +5; IVS1, G>A, +110; IVS2, C>G, +745; GLU6FS; VAL11FS; GLN39TER; HBD/HBB 104 kb del; and HBD87/HBB116 fusion). Since then, 57 more beta-thal chromosomes have been identified by the amplification-refractory mutation system (ARMS) and DNA sequencing from 54 individuals with beta-thalassemia (seven compound heterozygotes, three with two beta-thal alleles, three with beta-thal and HbS, and one with beta-thal and HbD; and 47 beta-thal heterozygotes). Nine of the previously observed alleles were found, together with three new alleles: IVS2, G>A, +1; LYS17TER; and 4-bp del, 41/42CTTT. Moreover, a novel mutation was observed, HIS77FS, bringing to a total of 17 beta-thal alleles identified in our population. Six alleles constitute 78.3% of the observed alleles: five Mediterranean alleles (GLN39TER; IVS1, G>A, +1; IVS1, G>A, +110; HBD/HBB 104 kb del; and IVS1, G>A, +5) and one common in the Kurdish population (-28A>C). We note especially the presence in these families of -28A>C and VAL11FS, both of which have previously been considered private alleles. The observed spectrum of mutations is characteristic of populations with low frequencies of thalassemias. Because thalassemia is not a rare disease in Mexico, we emphasize its necessary consideration in the differential diagnosis of microcytic hypochromic anemia.
Blood Cells Mol Dis
PMID:Molecular spectrum of beta-thalassemia in the Mexican population. 1531 94

Metalloproteinases have been characterised as "destroying bulldozers" in the extracellular matrix permitting normal remodelling and contributing to pathological tissue destruction. The opposing system is established by the Cadherin-beta-catenin system, which assures the integrity of the tissue. The EACC is an extremely rare disease in the field of Otolaryngology and its incidence is estimated about 1 per 1000 new otologic patients. The aim of this study is to characterise the balance between metalloproteinases and beta-catenin in EACC tissue. Twelve specimens were obtained during surgical removal of the EACC. The EACC- and AMS-specimens were immunostained with antibodies for beta-catenin, MMP-2 and MMP-9, respectively. Immunostaining for gelatinases was increased in all layers of the EACC. However, the normal auditory meatal skin presented moderate immunostaining. In the EACC specimens, the basal layers of the matrix were positive for beta-catenin. The suprabasal layers showed diminished or negative immunostaining for beta-catenin. In all layers the AMS was homogeneously positive for beta-catenin. Metalloproteinases can modulate the balance between cellular growth and apoptosis through cleavage of non-matrix, cell-surface substrates, such as the E-Cadherin-beta-catenin system. Furthermore, this balance guarantees the integrity of the tissue. Unbalanced conditions such as described in EACC, result in unregulated desquamation and accumulation of dead keratinocytes, invasive and defective growth into adjacent tissue, and loss of growth control. Generating synthetic inhibitors of metalloproteinases for therapeutic use in EACC and other defective diseases with unbalanced tissue conditions seems useful.
Int J Mol Med 2004 Oct
PMID:External auditory canal cholesteatoma: analysis of the integrity of the tissue structure. 1537 88

The external auditory canal cholesteatoma (EACC) is a rare disease with hyperproliferation and destructive growth in the adjacent structures. Down-regulation of beta-catenin (key component of the zonula adherens) is a pivotal factor for loose tissue integrity and invasiveness. Transforming growth factor beta1 (TGF-beta1) was reported to decrease beta-catenin in mammary epithelium. We investigated the abrogation of TGF-beta1 and beta-catenin expression in EACC culture cells. Cultured EACC-specimens were incubated with 6 micromol TGF-beta1 antisense. After 48 h, expression of beta-catenin was determined by means of immunohistochemistry. The cells showed an increased mural reactivity to beta-catenin, and intracellular reactivity was unchanged. The untreated cells showed a loss of beta-catenin expression at the membranes. The predominant membranous location after treatment with TGF-beta1 antisense suggests increased tendency of the cells for tissue formation and strong cell-cell adhesion rather than migratory and invasive character, and thus TGF-beta1 antisense application is a useful therapeutical strategy.
Int J Mol Med 2005 May
PMID:Up-regulation of beta-catenin in external auditory canal cholesteatoma. 1580 1

Rare syndromes often feature specific types of birth defects that frequently are major diagnostic clues to the presence of a given disorder. Despite this specificity, not everyone with the same syndrome is equally or comparably affected, and not everyone with a specific birth defect manifests the same syndrome or is affected with all the features of a particular syndrome. A symposium sponsored by the National Institutes of Health Office of Rare Diseases, and the National Toxicology Program Center for the Evaluation of Risks to Human Reproduction attempted to explore how much of this variability is due to genetic factors and how much is due to environmental factors. The specific types of birth defects examined included cardiovascular defects, holoprosencephaly, clefts of the lip and/or palate, neural tube defects, and diaphragmatic hernias.
Birth Defects Res A Clin Mol Teratol 2005 Nov
PMID:Gene-environment interactions in rare diseases that include common birth defects. 1626 46

Provision of health care to patients during and after events like those which occurred in association with hurricanes Katrina and Rita poses particular difficulties for rare disease patients, including those with genetic/metabolic diseases. In this summary, we recount the obstacles encountered in attempting to maintain and restore essential medical care to these patients, and offer proposals which may mitigate future such events.
Mol Genet Metab 2006 May
PMID:Genetic/metabolic health care delivery during and after hurricanes Katrina and Rita. 1631 Oct 54

A 52-year-old man suffering from a pure-type primary gastric small cell carcinoma was treated with surgery and combination chemotherapy. The small cell carcinoma, approximately 6.5 cm in diameter, was situated in the posterior wall of the antrum and there were no distant metastases. Total gastrectomy and regional lymph node dissection was carried out. Histological examination revealed a solid pattern of proliferation of small cells with hyperchromatic, round nuclei and scant cytoplasm. Neoplastic cells infiltrated into the subserosal layer with severe lymphatic and vascular invasion. Regional lymph node cells were mostly replaced by tumor cells that stained positive for Grimelius, neuron-specific enolase (NSE), and synaptophysin. Accumulations of electron-dense core granules in the small neoplastic cells were seen by electron microscopy. Following surgery, the patient was treated with adjuvant chemotherapy consisting of cisplatin and etoposide. The patient is alive and recurrence free 3 years after surgical operation. We review 107 published cases of primary gastric small cell carcinoma, an extremely rare disease first reported in 1976. Small cell carcinoma is an aggressive, malignant tumor. Intensive chemotherapy is essential for patient survival even when curative surgical resection is carried out.
Med Mol Morphol 2005 Dec
PMID:Primary gastric small cell carcinoma: report of a case and review of the literature. 1637 35

17alpha-Hydroxylase deficiency is a rare disease caused by mutation of the CYP17 gene, resulting in hypertension, hypokalemia, female sexual infantilism or male pseudohermaphroditism, low blood cortisol and low plasma renin activity. Herein, we report a female Taiwanese with 17alpha-hydroxylase deficiency. The CYP17 genes of this patient and five members of her family were analyzed by PCR-direct sequencing. One allele of the patient contains a 9-bp (c. 1459-1467 GACTCTTTC: D487, S488, F489) deletion, which is prevalent in Southeast Asia. The other allele has a 6-bp (c. 1480-1485 AAGGTG: K494, V495) deletion and an R496L (c. 1487 G>T) missense mutation, which is a novel mutation. Site-directed mutagenesis, in vitro expression and functional analysis in HEK-293T cells showed that this novel mutation [K494_V495 Del; R496L] resulted in complete loss of 17alpha-hydroxylase and 17,20-lyase activity. Thus this novel mutation in the extreme C-terminus abolishes enzyme activity, and when accompanied by a 9-bp deletion at codons 487-489 in the other allele, results in 17alpha-hydroxylase/17,20-lyase deficiency in this patient.
Mol Cell Endocrinol 2006 Apr 25
PMID:A novel compound heterozygous mutation of K494_V495 deletion plus R496L and D487_F489 deletion in extreme C-terminus of cytochrome P450c17 causes 17alpha-hydroxylase deficiency. 1648 11


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