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ID PMID Title PublicationDate abstract
15678895 [A case of pityriasis rubra pilaris associated with rapidly progressive finger joint destr 2004 Dec A 40-year-old female noticed edema of the lower limbs in March 1995. Nephrotic syndrome due to membranous nephropathy was diagnosed and administration of high-dose corticosteroids resulted in incomplete remission. Progressively enlarging, red scaling skin lesions developed concomitantly from the scalp to the extremities. Pityriasis rubra pilaris (PRP) was diagnosed in 1996 in the Department of Dermatology at Sapporo Medical University hospital. Various treatments proved ineffective. Arthritis of the finger joints developed in July 1999, and proteinuria recurred in April 2000. She was admitted to our department in August 2000. Physical examination on admission revealed marked swelling of both distal interphalangeal (DIP) joints and the right fourth proximal interphalangeal (PIP) joint. Results of testing for antinuclear antibody, rheumatoid factor, and HLA-B27 were all negative. Radiography of the hands revealed destruction of the DIP and PIP joints where MRI indicated the presence of synovitis. Bone scintigraphy demonstrated accumulation in bilateral metatarso-phalangeal joints and the left sacroiliac joint. Arthritis associated with PRP was diagnosed, as both PRP and psoriasis represent keratinizing disorders of the skin and clinical features in the present case resembled those of psoriatic arthritis. Despite administration of high-dose corticosteroids, destruction of finger joints progressed rapidly. Administration of cyclosporine in April 2002 improved arthritic symptoms. Cases of PRP accompanied by arthritis need to be accumulated to allow analysis of the pathogenesis and clinical picture of this association.
15260390 Psoriatic arthritis. 2003 Nov AIM OF THE STUDY: To evaluate the clinical pattern of psoriatic arthritis in patients attending a tertiary referral centre in South India. METHODOLOGY: Case records of one hundred and sixteen patients with psoriatic arthritis (PsA) who had attended our Rheumatology Department were analysed using demographic, clinical, laboratory and radiographic variables and the data were compared with other studies. RESULTS: Among 116 patients, 78 were males and 38 were females (ratio 2:1). Peak incidence (69%) was in the fourth and fifth decades. One patient had juvenile psoriatic arthritis (onset <16 years of age). Symmetric polyarthritis (48.3%) was the commonest subtype. Arthritis followed the skin lesions in 50.8% of patients, preceded in 12.1% and occurred simultaneously in 37.1%. Knee (66.4%) was the commonest joint involved. Extra-articular features like sausage digits (19%), enthesitis (7.8%) and eye manifestations (1.7%) like conjunctivitis and uveitis were observed. Psoriasis vulgaris (81%) was the commonest psoriatic lesion. Scalp (57.8%) was the most common hidden site. All the three patients with DIP arthritis alone had nail lesions. ESR and C-reactive protein were elevated in 51.7% and 43.9% of patients respectively. Rheumatoid factor was positive in 3.4 % and antinuclear antibody (ANA) was present in 5.4% (3/56) of patients. HIV infection was detected in 2.3% (1/44) of patients. Radiographic features like sacroiliitis (11.2%), calcaneal spur (7.8%), erosions (5.2%) and syndesmophytes (5.2%) were observed. One patient had 'pencil-in-cup deformity'. CONCLUSION: Psoriatic arthritis is more common in males. Symmetric polyarthritis is the commonest subtype. Arthritis commonly follows the skin lesions. Psoriasis vulgaris is the most common skin lesion and scalp is the commonest hidden site. ESR and CRP can be normal in psoriatic arthritis.
14558103 Induction of arthritis in SCID mice by T cells specific for the "shared epitope" sequence 2003 Oct OBJECTIVE: To study the immunologic function and determine the fine epitope structure of a synthetic peptide p135H ((2373)TTYKRRLQKRSSRHP) of the G3 domain of human cartilage proteoglycan (aggrecan), which contains a highly homologous sequence motif of the shared epitope (QKRAA), the most common sequence motif in HLA-DR4 alleles, which predispose humans to the development of rheumatoid arthritis (RA). METHODS: Synthetic p135 peptides with altered sequences were used for (hyper)immunization of arthritis-susceptible BALB/c mice and then challenged with a single dose of cartilage proteoglycan. Human p135 (p135H) and mouse p135 (p135M) synthetic peptides of the G3 domain of aggrecan were used to prime lymphocytes, which were then used for adoptive transfer of arthritis into "presensitized" SCID mice, determining cross-reactivity among p135 peptides and their analogous sequences, and generating T cell hybridomas. T cell hybridomas were also used for arthritis transfer into SCID mice and for characterizing the fine epitope structure of T cell receptor (TCR) and major histo-compatibility complex (MHC) binding sites of the immunogenic/arthritogenic p135H sequence. RESULTS: While p135H peptide-(hyper)immunized mice became sensitized, they developed arthritis only after injection of a single dose of cartilage proteoglycan aggrecan. An altered peptide sequence (p135H-AA) carrying the shared epitope motif (QKRAA) was as effective as the natural peptide p135H sequence for inducing arthritis. Mouse p135M-specific lymphocytes induced arthritis with a lower incidence, but synthetic peptides to Escherichia coli heat-shock protein (DnaJ) or HLA-DR4 allele (both having the shared epitope sequence with different flanking regions) were also positive. Fine epitope sequence recognition of an arthritogenic T cell hybridoma derived from p135H-primed lymphocyte population was determined. Interestingly, in the most central position, a basic amino acid triplet of p135H peptide was found to be the MHC-binding motif, whereas the flanking amino acids bound to the TCR. CONCLUSION: Peptide p135H, corresponding to the peptide sequence in the G3 domain of human cartilage proteoglycan aggrecan, is immunogenic/arthritogenic in BALB/c mice. Peptide p135H includes a highly homologous motif of the shared epitope, a sequence that is overrepresented in bacterial heat-shock proteins, envelope protein of human JC polyomavirus, and numerous HLA-DR4 alleles. Since the G3 domain of cartilage proteoglycan aggrecan with the p135 sequence is "lost" during the normal metabolic turnover of cartilage proteoglycan or in pathologic conditions, an antigenoriented T cell migration into joints of presensitized (susceptible) individuals may contribute to the organ-specificity of RA.
12092767 Grading of chronic synovitis--a histopathological grading system for molecular and diagnos 2002 The following is a proposition for a simple histopathological classification system to measure inflammation in synovial tissue. This synovitis-score is employed in conventionally stained routine sections, and is applicable to every kind of synovitis, irrespective of etiology and including the following relevant morphological alterations. First: hyperplasia/enlargement of synovial lining cell layer. Second: activation of resident cells/synovial stroma. Third: inflammatory infiltration. All defined histopathological qualities are graded from absent (0), slight (1) and moderate (2) to strong (3), with summaries ranging from 0 to 9. 0 to 1 corresponds to no synovitis (inflammatory grade = 0), 2 to 3 to a slight synovitis (inflammatory grade 1), 4 to 6 to a moderate synovitis (inflammatory grade 2), and 7 to 9 to a strong synovitis (inflammatory grade 3). Using this score, we analyzed 308 random specimens of synovial tissue from degenerative (osteoarthritis (OA)) and inflammatory joint diseases - reactive arthritis (ReA), psoriasis arthritis (PA) and rheumatoid arthritis (RA) - as well as synovial tissue from healthy individuals. The mean grade given to synovitis of RA turned out to be significantly higher than the mean grade of OA (p < 0.0005) and of healthy controls (p < 0.0005). On the contrary, no significant differences could be found between the mean grades of synovitis scores from patients with RA and those with PA and ReA. Another comparison between RA-synovitis types I and II according to the Stiehl classification resulted in type I (p < 0.0005), showing significantly higher values of inflammatory infiltration, and type II (p = 0.037), showing significantly higher values of stroma activation. Since in OA, synovitis is regarded as a result of degenerative cartilage destruction whereas in inflammatory joint diseases (RA, PA, ReA), synovitis is regarded to be the cause of cartilage destruction, it can be concluded that scores with considerable high values indicate the pathogenetic potential of synovitis and that the inflammatory score may be helpful in estimating the destructive potential of synovitis at the same time. Furthermore, the comparison of the score data with the Stiehl RA-synovitis types shows that the score enables us to discriminate the morphological peculiarities of the synovitis types. In experimental pathology, it could provide standardized information on molecular synovial tissue analyses where a correlation of molecular with morphological data is essential. In diagnostic pathology, this synovitis score (in combination with other typing systems) could provide basic and standardized information concerning the degree of inflammatory alterations in synovial tissue.
11992858 Goniotomy for glaucoma secondary to chronic childhood uveitis. 2002 May PURPOSE: To evaluate the safety and efficacy of standard goniotomy surgery for young patients with refractory glaucoma associated with chronic childhood uveitis. DESIGN: Interventional case series. METHODS: We retrospectively reviewed all goniotomies performed at our institution for patients with a diagnosis of refractory glaucoma associated with chronic childhood uveitis from 1994 to 2000 (this was our first-line surgery for such patients during these years). Uveitis was medically controlled in all cases for at least 6 weeks before surgery. The main outcome measure was time after surgery without failure. Success was defined as final intraocular pressure (IOP) or=6 months or until surgical failure. RESULTS: Nineteen goniotomies were performed on 16 eyes (12 patients). Diagnoses included uveitic glaucoma associated with juvenile rheumatoid arthritis, sarcoidosis, and idiopathic uveitis. The mean patient age at first goniotomy was 15.3 years (range, 6.5-30), with mean follow-up 32.4 months (range, 6-84). Cases included were phakic (10 eyes), aphakic (four eyes), and pseudophakic (two eyes). The mean preoperative IOP was 32.3 +/- 4.6 mm Hg. Surgical success was achieved in 12 of 16 (75%) eyes with a mean postoperative IOP of 12 +/- 2.5 mm Hg for these eyes (mean IOP reduction, 20.0 mm Hg, P <.0001). In 10 of 16 eyes (60%), surgical success was achieved after a single goniotomy. Uveitis was stable in all patients after the early post-operative period. Successful eyes used, on average, 1.4 +/- 1.1 glaucoma medications after goniotomy. Complications were mild and included transient hyphema in nine cases (56%) and worsening of a preexisting cataract in a single case (6%). CONCLUSIONS: Goniotomy represents a safe and effective first-line surgery for young patients with refractory glaucoma associated with chronic uveitis, although the majority of patients require glaucoma medication after the procedure.
15197058 Goniosurgery for glaucoma complicating chronic childhood uveitis. 2004 Jun OBJECTIVES: To describe the safety and efficacy of goniotomy in medically uncontrolled glaucoma complicating chronic uveitis and the factors affecting its outcome. METHODS: All goniotomies performed by a single surgeon for refractory childhood uveitic glaucoma were retrospectively reviewed. Success was defined as final intraocular pressure (IOP) of no greater than 21 mm Hg without medications and qualified success as IOP of no greater than 21 mm Hg with medications. Unless otherwise indicated, data are expressed as mean +/- SD. RESULTS: Fifty-four goniotomies were performed in 40 eyes of 31 patients. Juvenile rheumatoid arthritis-associated uveitis was the diagnosis in 30 eyes (75%). Eleven eyes (28%) were aphakic. Mean follow-up was 98.9 months (range, 2-324 months). Mean age at surgery was 10.3 +/- 4.7 years (range, 4-22 years). Mean preoperative IOP was 36.7 +/- 6.4 mm Hg while receiving a mean of 2.9 +/- 1.1 medications. Overall surgical success was achieved in 29 eyes (72%), including success in 22 (55%) and qualified success in 7 (18%) while receiving a mean of 1.6 +/- 1.1 medications. Mean postoperative IOP in the success and qualified-success groups were 14.3 +/- 2.8 and 15.7 +/- 3.1 mm Hg, respectively. Kaplan-Meier survival probabilities (95% confidence interval) at 1, 5, and 10 years were 0.92 (0.82-1.00), 0.81 (0.65-0.97), and 0.71 (0.49-0.92), respectively. Phakic eyes, eyes with fewer peripheral anterior synechiae, patients younger than 10 years, and eyes with no prior surgery had significantly better outcomes. Hyphema, typically mild and transient, occurred in 43 procedures (80%). CONCLUSIONS: Goniosurgery is low risk and effective for refractory glaucoma complicating chronic childhood uveitis. It should be considered the surgical procedure of choice for this condition. Surgical outcome is adversely affected by increased age, peripheral anterior synechiae, prior surgeries, and aphakia.
11971877 Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an 2002 Apr 15 PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne, OMIM #604416) and familial recurrent arthritis (FRA) are rare inherited disorders of early onset, primarily affecting skin and joint tissues. Recurring inflammatory episodes lead to accumulation of sterile, pyogenic, neutrophil-rich material within the affected joints, ultimately resulting in significant destruction. We recently localized the genes for PAPA syndrome and FRA to chromosome 15q and suggested that they are the same disorder. We have now established this by the identification of co-segregating disease-causing mutations in the CD2-binding protein 1 (CD2BP1; GenBank accession no XM 044569) gene in the two reported families with this disorder. E250Q or A230T amino acid substitutions occur within a domain highly homologous to yeast cleavage furrow-associated protein CDC15. CD2BP1 and its murine ortholog, proline-serine-threonine phosphatase interacting protein (PSTPIP1), are adaptor proteins known to interact with PEST-type protein tyrosine phosphatases (PTP). Yeast two-hybrid assays demonstrate severely reduced binding between PTP PEST and both the E250Q and A230T mutant proteins. Previous evidence supports the integral role of CD2BP1 and its interacting proteins in actin reorganization during cytoskeletal-mediated events. We hypothesize that the disease-causing mutations that we have identified compromise physiologic signaling necessary for the maintenance of proper inflammatory response. Accordingly we suggest classification of PAPA syndrome as an autoinflammatory disease. This CD2BP1-mediated biochemical pathway(s) may function in common inflammatory disorders with apparent etiological overlap, such as rheumatoid arthritis and inflammatory bowel disease.
12010572 Differential binding of chemokines to macrophages and neutrophils in the human inflamed sy 2002 In chronic inflammatory foci, such as the rheumatoid joint, there is enhanced recruitment of phagocytes from the blood into the tissues. Chemokines are strongly implicated in directing the migration of these cells, although little is known regarding the chemokine receptors that could mediate their chemotaxis into the joint tissue. Therefore the objective of the study was to identify chemokine binding sites on macrophages and neutrophils within the rheumatoid synovium using radiolabeled ligand binding and in situ autoradiography. Specific binding sites for CCL3 (macrophage inflammatory protein-1alpha), CCL5 (RANTES), CCL2 (monocyte chemoattractant protein-1) and CXCL8 (IL-8) were demonstrated on CD68+ macrophages in the subintimal and intimal layers. The number and percentage of intimal cells that bound chemokines were greater in inflamed regions compared to noninflamed regions. The intensity of intimal binding varied between chemokines with the rank order, CCL3 > CCL5 > CCL2 > CXCL8. Neutrophils throughout the synovium bound CXCL8 but did not show any signal for binding CCL2, CCL3 or CCL5. Immunohistochemistry showed that both CXCR1 and CXCR2 are expressed by macrophages and neutrophils in the rheumatoid and nonrheumatoid synovia, suggesting that both of these receptors are responsible for the CXCL8 binding. The chemokine binding sites described on phagocytes may be involved in the migration of these cells into the inflamed joint.
15507385 Estrogen as an immunomodulator. 2004 Dec Estrogen's role in the sex differences observed in autoimmune diseases such as systemic lupus, multiple sclerosis, and rheumatoid arthritis have remained unclear. Complicating the understanding of the immunomodulatory effects of estrogen are (1) the effects of estrogen on multiple components of the immune response; (2) its varied effects on different systems in which it appears pro-autoimmune, as in murine lupus, or anti-inflammatory, as in EAE; and (3) its effects on other hormones which are potentially immunomodulatory. Recent reports have shed light on the role of estrogen in the modulation of lymphocyte survival and expansion and in the elaboration of Th1 versus Th2 cytokines and on the mechanisms by which estrogen can activate via multiple signaling and genomic pathways in immune cells.
14768374 [A case of pulmonary Mycobacterium gordonae infection with pleural effusion]. 2004 Jan A 65-year-old woman, treated with prednisolone (5 mg daily) for rheumatoid arthritis, visited our hospital because of right chest pain. Chest CT showed small nodular shadows in the right lung accompanied with right pleural effusion. A pulmonary Mycobacterium gordonae infection was diagnosed, since M. gordonae was identified twice from her sputum. She was treated with rifampicin, ethambutol and streptomycin for two months, and then streptomycin was replaced with clarithromycin. Three months after the initial treatment, M. gordonae was eradicated from her sputum. Pleural puncture revealed bloody, exudative, lymphocytotic pleural effusion, but no malignant cells were identified. Although pathological diagnosis by thoracoscopic pleural biopsy could not be performed, it is likely that the pleural effusion was associated with the pulmonary M. gordonae infection in the present case.
14566744 Ninety-day mortality after shoulder arthroplasty. 2003 Oct Although mortality associated with knee and hip arthroplasty has been reported, there is no information about shoulder arthroplasty. The purpose of this study was to determine the incidence and risk factors associated with perioperative mortality after shoulder arthroplasty. Between 1970 and 2000, 2,953 patients underwent shoulder arthroplasty at our institution. A retrospective review identified all patients who died within 90 days of the procedure. The 90-day mortality incidence was 0.58% (17 of 2,953). Twelve hemiarthroplasties were performed for a pathologic fracture and one for rotator cuff arthropathy. Total shoulder arthroplasties were performed for the sequelae of trauma (2), rheumatoid arthritis (1), and avascular necrosis (1). Ninety-day mortality was closely associated with the underlying diagnosis. Perioperative mortality after shoulder arthroplasty for non-neoplastic conditions is low.
24387209 Assessment of inflamed synovial membrane in the knee joint by dynamic magnetic resonance i 2003 Sep Abstract Dynamic magnetic resonance imaging (dynamic MRI) was used to examine the synovial membrane in the knee joints of 15 patients with rheumatoid arthritis (RA) in order to investigate the relationship between pathological and MRI findings. Signal intensities in the regions of interest (ROI), identified as the synovial membrane of the suprapatellar pouch, were measured on MR images. Signal intensities at various times after the injection of contrast medium Gd-diethylenetriaminopentoacetic acid (Gd-DTPA) were normalized relative to the signal intensity at 80 s, and designated as the normalized signal intensity (NSI). Pathological findings were quantified, and the types of inflamed synovial membrane were classified as either acute or chronic. A significant difference in NSI was observed between acute and chronic types (P < 0.05). Dynamic MRI was capable of classifying acute and chronic RA by measuring NSI 20 s after contrast medium injection. Dynamic MRI was therefore shown to be useful for assessing regional synovial inflammation.
12822354 [Application of gene therapy mediated by adenovirus vectors for bone trauma and bone disea 2003 May OBJECTIVE: To review the current concepts of gene therapy approaches mediated by adenovirus vectors for bone trauma and bone disease. METHODS: The recent literature concerned gene therapy mediated by adenovirus vectors was reviewed, which provides new insights into the treatments of bone trauma and bone disease. RESULTS: Adenovirus vectors was efficient, achieved high expression after transduction, and could transfer genes to both replicating and nonreplicating cells, such as osteoblasts, osteoclasts, fibroblasts, chondrocytes, bone marrow stromal cells, etc. Gene therapy mediated by adenovirus vectors achieved affirmative results in enhancing bone union and in curing bone diseases, such as osteoporosis and rheumatoid arthritis. CONCLUSION: Gene therapy mediated by adenovirus offers an exciting avenue for treatment of bone trauma and bone diseases.
12669471 Anti-interferon-gamma antibodies in the treatment of autoimmune diseases. 2003 Feb Interferon (IFN)-gamma is an important immune regulator in normal immunity. When IFN gamma production is disturbed, various autoimmune diseases (ADs) can develop, in which we suggest that anti-IFN gamma could have a beneficial effect. Depending on the cell type in which IFN gamma synthesis is disturbed, different clinical manifestations may result. We have also proposed to remove tumor necrosis factor (TNF)-alpha, together with certain types of IFNs, to treat various ADs and AIDS, also an autoimmune condition. Anti-IFN gamma has been tested in several T-helper cell (Th1) ADs, including rheumatoid arthritis (RA), multiple sclerosis (MS), corneal transplant rejection, uveitis, Type I diabetes, schizophrenia (anti-IFN gamma and anti-TNF alpha), and various autoimmune skin diseases (alopecia areata, psoriasis vulgaris, vitiligo, pemphigus vulgaris and epidermolysis bullosa). A strong, sometimes striking, therapeutic response followed administration of anti-IFN gamma, indicating that it may be a promising therapy for Th1 ADs.
12510956 A hyaluronan preparation (500-730 kDa) in the treatment of osteoarthritis: a review of cli 2002 Dec The purpose of this paper is to review the intra-articular treatment of osteoarthritis (OA) of the knee with the hyaluronan preparation 500-730 kDa (Hyalgan). Reviewing the results of 24 clinical trials, it can be concluded that 3-5 weekly injections of Hyalgan significantly improve the pain and functional status of patients with OA. Although the onset of improvement is delayed by 3-4 weeks, the effect can last at least six months and up to one year after treatment cessation. The benefits of Hyalgan compared with intra-articular corticosteroids are also addressed. The potential for Hyalgan to have a structure-modifying action by retarding stuctural progression in OA of the knee is considered. However, further studies of Hyalgan in OA in other joints, and in damaged joints in rheumatoid arthritis, are needed.
19719658 Bacterial composition of murine fecal microflora is indigenous and genetically guided. 2003 May 1 Abstract The gastrointestinal tract and the microbes colonizing it form a complex ecosystem that has various effects on the well-being of the host. In addition to acute infections, the composition of the gastrointestinal microbiota has been suspected to influence the etiopathogenesis of many chronic diseases, such as rheumatoid arthritis and inflammatory bowel diseases. It has been suggested that the bacterial colonization of the gastrointestinal tract is genetically determined. Using gas-liquid chromatography of bacterial cellular fatty acids we show in this study that modulation of the microbiota by a course of antibiotics is followed by regeneration of the murine intestinal flora depending on the genotype of the host. The mice used in our study were acclimatized to identical living conditions before treatment with ciprofloxacin and clindamycin for 1 week via drinking water. Within a few days of finishing the antibiotic course, the cellular fatty acid profiles of fecal samples resembled those of the pre-course community, showing a considerable indigenous recovery potential. Colonization of the gastrointestinal tract appeared to be genetically regulated since differences in communities between the mouse strains were observed. Our results are in harmony with earlier observations, indicating that the gut community is not established by chance and that it is influenced by host-derived factors.
12594107 HLA class II is associated with distal interphalangeal osteoarthritis. 2003 Mar OBJECTIVE: To investigate whether there is an association between HLA class II and distal interphalangeal osteoarthritis (DIP OA). METHODS: The study group consisted of consecutive patients with and without DIP OA aged between 40 and 70 years. DIP OA was diagnosed by radiology. These patients were referred to an "Early Arthritis Clinic" (EAC) with different types of arthritis at an early stage. Patients with rheumatoid arthritis, systemic lupus erythematosus, spondyloarthropathies, and psoriatic arthritis were excluded for the purpose of this study. DNA typing for HLA-DR and x ray examination of the hands were performed at enrollment in the EAC. To establish whether the study group was representative of the Dutch population, a population based study in Zoetermeer (n=3243) for the prevalence of DIP OA and blood donors in the Leiden area (n=2400) for the HLA-DR antigen frequencies were used as references. RESULTS: Fifty five patients (33%) of the total study group (n=166) had DIP OA. The prevalence of DIP OA and frequency of the HLA-DR alleles were similar to those of the two reference groups. Within the study group an association between DIP OA and HLA-DR2 and DR4 with respectively odds ratios of 2.4 (95% confidence interval (CI) 1.1 to 5.0) and 0.3 (95% CI 0.1 to 0.7) was found. No association was found between other HLA-DR alleles and DIP OA. CONCLUSION: The study group is a representative sample of the Dutch population. The HLA-DR2 allele was more common in patients with DIP OA. Furthermore, an inverse relation was observed between DIP OA and HLA-DR4. The results confirm findings from other investigations implicating HLA-DR2 as a risk factor in the development of DIP OA.
16088537 Genetics of idiopathic disseminated bronchiectasis. 2003 Apr Bronchiectasis is an abnormal dilation of bronchi, consequent to the destruction of their walls. It is included in the category of obstructive pulmonary diseases, along with chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis. In approximately 50% of cases, bronchiectasis is associated with underlying conditions; in the remainder, known causes are not ascertainable (idiopathic bronchiectasis). A search for genetic determinants of this phenotype, with the cystic fibrosis gene as a candidate, has been performed by three independent groups. The results of this search agreed on the association of bronchiectasis with cystic fibrosis gene mutations and polymorphisms. The cystic fibrosis gene is also associated with bronchiectasis due to rheumatoid arthritis and allergic bronchopulmonary aspergillosis. A few other genes have been investigated in idiopathic bronchiectasis, with negative results. Idiopathic bronchiectasis is, therefore, to be considered as an obstructive multifactorial disorder belonging to the category of cystic fibrosis monosymptomatic diseases (or CFTR-opathies), whose pathogenesis is influenced by environmental factors and other undetermined genes.
15523815 [The ubiquitin system for intracellular protein degradation--involvement in human patholog 2004 Aug The ubiquitin-proteasome pathway has a central role in selective degradation of intracellular proteins. Among the key proteins that are degraded by the system are those involved in the control of inflammation, cell cycle regulation, and gene expression. With so many important cellular pathways affected, derangements in the ubiquitin system have been shown to result in a variety of human diseases. Consequently, proteasome inhibition has a potential as a form of treatment for many human diseases such as cancer and inflammatory conditions. Two proteasome inhibitors, PS-341 and PS-519 are currently under clinical evaluation. PS-341 is currently being evaluated in phase III clinical trial for multiple myeloma, and PS-519 is now on a phase II trial for acute ischemic stroke. In addition, inhibition of the proteasome has been shown to be effective in several animal models for a variety of human diseases such as different malignancies, asthma, rheumatoid arthritis, and arterial restenosis. Future studies will be required to establish whether the promising animal studies could be successfully implicated in human disease states.
15316443 Cancer and interstitial lung disease. 2004 Sep PURPOSE OF REVIEW: This review assesses the contribution of various conditions that cause interstitial lung disease to the development of cancer. RECENT FINDINGS: Interstitial lung diseases for which the available evidence suggests an increased risk of lung cancer include idiopathic pulmonary fibrosis, systemic sclerosis, and certain forms of pneumoconioses. The pathogenesis of lung cancer remains unclear, and the available data on inflammation-induced pulmonary fibrosis as a risk factor for lung cancer are summarized. There is inadequate evidence for any conclusions about the risk of solid tumors and hematologic malignancies in patients with sarcoidosis, rheumatoid arthritis, and systemic lupus erythematosus. An increased incidence of lymphoma is detected in Sjögren's syndrome. For patients with dermatomyositis and polymyositis, there is a well-documented association with a wide range of cancers. SUMMARY: Further studies are needed to clarify the cause(s) and the mechanisms that link various interstitial lung diseases and cancer.