Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hermansky-Pudlak syndrome (HPS) is a disorder of lysosome-related organelles such as melanosomes and platelet dense granules. Seven genes are now associated with HPS in humans. An accurate diagnosis of each HPS subtype has important prognostic and treatment implications. Here we describe the cellular, molecular, and clinical aspects of the recently identified HPS-5 subtype. We first analyzed the genomic organization and the RNA expression pattern of HPS5, located on chromosome 11p14, and demonstrated tissue-specific expression of at least three alternatively spliced HPS5 mRNA transcripts, coding for HPS5A and HPS5B proteins, that differ at their 5'-ends. Genetic screening of 15 unassigned HPS patients yielded six new HPS5 mutations in four patients. Clinically, our HPS-5 patients exhibited iris transillumination, variable hair and skin pigmentation, and absent platelet dense bodies, but not pulmonary fibrosis or granulomatous colitis. In two patients with homozygous missense mutations, hemizygosity was ruled out by gene-dosage multiplex polymerase chain reaction, and immunocytochemical analyses of their fibroblasts supported the HPS-5 diagnosis. Specifically, LAMP-3 distribution was restricted to the perinuclear region in HPS-5 fibroblasts, in contrast to the normal LAMP-3 distribution, which extended to the periphery. This specific intracellular vesicle distribution in fibroblasts, in combination with the clinical features, will improve the characterization of the HPS-5 subtype.
 ...
PMID:Cellular, molecular and clinical characterization of patients with Hermansky-Pudlak syndrome type 5. 1529 95

Idiopathic pulmonary fibrosis (IPF), a chronic form of idiopathic interstitial pneumonia, has a poor prognosis with an average life expectancy of 3-4 years from the time of diagnosis. Although patients with IPF have been treated with steroids or immunosuppressants to control the inflammation that occurs earlier in the course of disease, these drugs have not improved the survival of patients with IPF. Recently, several clinical studies of antifibrotic drugs have been conducted in patients with IPF. In Japan, we demonstrated that pirfenidone prevents deterioration of pulmonary function and significantly decreases the incidence of acute exacerbation of IPF in a well-designed, placebo-controlled, double-blind, randomized study. We have also adopted a new system for evaluation of dynamic pulmonary function, which involves measuring the lowest SpO2 level during a 6-minute walk at a constant speed and assessing the pulmonary capacity of patients with IPF. In a study of patients with pulmonary fibrosis associated with Hermansky-Pudlak syndrome in the United States, pirfenidone slowed the decrease in %FVC in patients with a %FVC of >60%, but had no significant effects on patients with a %FVC of < or =60%. Large-scale clinical studies of INF-gamma in patients with IPF in North America and Europe have reported decreases in the mortality of patients with mild IPF with a FVC of >60%, although percentages of patients with disease status rated as 'exacerbated', 'unchanged' and 'improved' after treatment did not differ between the INF-gamma and placebo groups. This presentation reported important future strategies for the treatment of IPF.
 ...
PMID:[Expectation of new treatments for idiopathic interstitial pneumonias]. 1573 51

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, a bleeding diathesis and, in some patients, pulmonary fibrosis or granulomatous colitis. HPS is associated with biosynthesis defects of melanosomes, platelet-dense bodies, and lysosomes. There are seven genetic HPS subtypes; HPS-1 is the most common. We used a real-time quantitative PCR (qPCR) approach to investigate six HPS-1 patients, previously assigned as having homozygous mutations in the HPS1 gene. HPS1 gene copy numbers, calculated by use of a comparative Ct method, revealed that one patient was in fact hemizygous for her c.1189delC (S396delC) HPS1 mutation. The causative deletion/insertion was 13,966 bp in size, with defined breakpoints, and involved an adjacent gene (C10orf33). A mechanism of formation is proposed for the deletion/insertion, and both multiplex and qPCR indicated that the deletion/insertion was present in the patient, her brother, and her father. qPCR amplification is valuable for detecting deletions too small to be identified by fluorescence in situ hybridization. This demonstration of hemizygosity, performed using genomic DNA, can eliminate concerns about non-paternity and can verify the diagnosis of an autosomal recessive disorder when a DNA alteration appears to be homozygous by standard PCR and sequencing methods, and its pathogenicity is in doubt.
 ...
PMID:Detection of hemizygosity in Hermansky-Pudlak syndrome by quantitative real-time PCR. 1595 82

Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by oculocutaneous albinism, a bleeding diathesis, and in a subset of patients, pulmonary fibrosis. Lung transplantation, the only curative therapy for pulmonary fibrosis, has not been previously reported as a successful treatment strategy for patients with HPS because the bleeding diathesis was thought to contraindicate major thoracic surgery. We successfully performed bilateral sequential lung transplantation in a patient with pulmonary fibrosis and HPS after transfusion of 6 units of platelets. Lung transplantation is a viable therapeutic option in patients with pulmonary fibrosis and only a mild bleeding diathesis associated with HPS.
 ...
PMID:Successful bilateral lung transplantation for pulmonary fibrosis associated with the Hermansky-Pudlak syndrome. 1621 Jan 49

The Hermansky-Pudlak syndrome (HPS) is a collection of related autosomal recessive disorders which are genetically heterogeneous. There are eight human HPS subtypes, characterized by oculocutaneous albinism and platelet storage disease; prolonged bleeding, congenital neutropenia, pulmonary fibrosis, and granulomatous colitis can also occur. HPS is caused primarily by defects in intracellular protein trafficking that result in the dysfunction of intracellular organelles known as lysosome-related organelles. HPS gene products are all ubiquitously expressed and all associate in various multi-protein complexes, yet HPS has cell type-specific disease expression. Impairment of specialized secretory cells such as melanocytes, platelets, lung alveolar type II epithelial cells and cytotoxic T cells are observed in HPS. This review summarizes recent molecular, biochemical and cell biological analyses together with clinical studies that have led to the correlation of molecular pathology with clinical manifestations and led to insights into such diverse disease processes such as albinism, fibrosis, hemorrhage, and congenital neutropenia.
 ...
PMID:Hermansky-Pudlak syndrome: a disease of protein trafficking and organelle function. 1642 Feb 44

Hermansky-Pudlak syndrome (HPS) is a rare heterogeneously inherited autosomal recessive group of disorders presenting with oculocutaneous albinism, bleeding diathesis and pulmonary disease. HPS is thought to occur as a consequence of disturbed formation or trafficking of intracellular vesicles, most importantly, melanosomes, platelet dense granules and lysosomes. The latter finding, in particular, contributes much to the morbidity associated with the disease, as ceroid lipofuscin deposits in lysosomes affect many organ systems. This is especially problematic in the lungs where it is often associated with pulmonary fibrosis and premature death. Currently, there are 7 known HPS genes in humans. In the mouse, at least 16 known HPS genes produce HPS-mutant phenotypes. The HPS gene mutation is considered to be one of the most prevalent single-gene disorders in northwest Puerto Rico, home to the largest cohort of known patients. In HPS, interventions addressing the bleeding diathesis and pulmonary fibrosis are often disappointingly ineffectual. Pirfenidone, a novel compound with documented anti-inflammatory, antioxidant and antifibrotic effects, appears to hold promise in delaying or preventing fibrosis. To date, there has been one successful lung transplant performed on a patient with HPS. We present a patient with HPS and review the current literature on our understanding of this rare disorder.
 ...
PMID:Pulmonary fibrosis in hermansky-pudlak syndrome. a case report and review. 1649 Sep 34

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and platelet dysfunction. A subset of patients also show ceroid deposition, which can result in pulmonary fibrosis or granulomatous colitis. Whether this colitis may be considered Crohn's disease is under debate. We report a case of a patient with HPS associated with inflammatory bowel disease which affected the distal small bowel but not the colon. Ileitis was severe, and recurred rapidly after surgery. Search for mutations in HPS1, ADTB3A, HPS3, HPS4 and for CARD15 were negative. Symptoms and ileal ulcerations which recurred after surgery were successfully treated with azathioprine and infliximab.
 ...
PMID:Ileal Crohn's disease in a woman with Hermansky-Pudlak syndrome. 1673 90

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder which is characterised by the triad of oculocutaneous albinism, platelet dysfunction and accumulation of ceroidlike pigment in tissues. Complications of the syndrome, such as fatal pulmonary fibrosis, renal failure and cardiomyopathy have been described. Granulomatous colitis has been documented in several families with the HPS. The bowel disease of the HPS is a unique type of inflammatory bowel disease with clinical features suggestive of idiopathic ulcerative colitis (UC) and pathologic features suggestive of Crohn's disease. We report a patient with HPS which was complicated by granulomatous colitis with perineal and rectovaginal fistulas refractory to antibiotics and azathioprine but dramatically responded to repeated infusions of infliximab.
 ...
PMID:Complicated granulomatous colitis in a patient with Hermansky-Pudlak syndrome, successfully treated with infliximab. 1692 18

A 55-year-old female patient with Hermansky-Pudlak syndrome (albinism, thrombopathia and ceroid accumulation) underwent a single lung transplantation for pulmonary fibrosis. Examination of explanted lung showed usual interstitial pneumonia pattern associated with two unusual lesions: presence of numerous macrophages containing ceroid pigments within fibrosis and characteristic foamy swelling of pneumocytes. This later lesion, which has only been recently described, seems related to the mechanism of the disease by defect of surfactant secretion. This lesion allows the histological individualization of pulmonary fibrosis associated with Hermansky-Pudlak syndrome from idiopathic usual interstitial pneumonia.
 ...
PMID:[Pulmonary fibrosis in Hermansky-Pudlak syndrome is not fully usual]. 1725 4

Asbestos and benzo(a)pyrene diol epoxide (BPDE) are pulmonary carcinogens with synergistic interaction in causing lung cancer. We used Affymetrix microarrays to study gene modulation in vitro using normal human bronchial epithelial cells exposed to chrysotile asbestos and/or BPDE for 4 or 24 h. Linear models were used to compare treated cells to controls at each time point to identify statistically significant up- or downregulation of genes. Profiles of genes regulated by chrysotile were dominated by cytokines, growth factors, and DNA damage. Profiles of genes with BPDE and chrysotile regulation were correlated with proliferation, DNA damage recognition and nucleotide-excision repair, cytokines, and apoptosis. Chemokines, growth-regulated oncogene-alpha (Gro-alpha, CXCL-1), and IL-8, were significantly increased, and these had previously been observed in bronchoalveolar lavage from asbestos workers or in animal models. Interestingly, the Hermansky-Pudlak gene, which is mutated in an autosomal recessive form of pulmonary fibrosis, was downregulated threefold by BPDE at 4 h. This is an interesting example of gene (Hermansky-Pudlak syndrome) and environment (BPDE) interaction. Transcription factors, including activating transcription factor 3 and Cbp/p300-interacting transactivator, were upregulated by chrysotile. Real Time PCR for IL-8, ATF-3, GADD45B, CXC Ligand 1, and CTGF compared to GAPDH validated microarray findings at 24 h. These in vitro findings in NHBE cells model environment-gene interaction for asbestos and BPDE, highlighting effects of inflammation, fibrosis, proliferation, and DNA damage recognition and repair.
 ...
PMID:Gene profiling of normal human bronchial epithelial cells in response to asbestos and benzo(a)pyrene diol epoxide (BPDE). 1819 26


<< Previous 1 2 3 4 5 6 7 8 9 Next >>