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M Ameen

Bio: M Ameen is an academic researcher from St. John's University. The author has contributed to research in topics: Medicine & Psoriasis. The author has an hindex of 8, co-authored 11 publications receiving 925 citations.

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M Ameen1
TL;DR: Global patterns of dermatophyte infection and the changing epidemiology of the causative agents are discussed.

348 citations

Journal ArticleDOI
TL;DR: In this article, a comparison of CDSN intragenic haplotypes showed that SNPs exclusive to disease-associated chromosomes are located in regions implicated in the stabilization of RNA transcripts.
Abstract: Psoriasis is a chronic skin disorder with multifactorial aetiology. Genome-wide scans have provided unambiguous evidence for a major disease susceptibility locus on chromosome 6p21 (PSORS1). A minimal PSORS1 interval has been defined which encompasses three genes (HLA-C, HCR and CDSN) carrying psoriasis-associated SNPs. On the basis of this genetic evidence, we have undertaken an assessment of CDSN allele functional impact. A comparison of CDSN intragenic haplotypes showed that SNPs exclusive to disease-associated chromosomes are located in regions implicated in the stabilization of RNA transcripts. As CDSN is over-expressed in psoriatic lesions, we hypothesised that disease-associated intragenic SNPs may alter the rate of its mRNA decay. Here, we demonstrate that mRNAs transcribed from a CDSN risk haplotype present a 2-fold increase in stability, compared with those transcribed from a neutral haplotype (t-test P = 0.004). Site-directed mutagenesis revealed that a single synonymous SNP (CDSN*971T) accounts for the observed increase in RNA stability. CDSN*971T maps to a RNA stability motif and UV cross-linking analysis demonstrated that the SNP affects the transcript affinity for a 39 kDa RNA binding protein. Association analyses show that haplotypes bearing CDSN*971T confer psoriasis susceptibility in a wide range of ethnic groups. These results demonstrate the effect of synonymous variation upon allele specific gene expression, a finding of relevance to future studies of the pathogenesis of common and complex traits.

275 citations

Journal ArticleDOI
01 Apr 2003
TL;DR: The PSORS1 locus in the major histocompatibility complex region is the major genetic determinant for psoriasis vulgaris as discussed by the authors, and it has been shown that specific allelic variants of the genes HLA-Cw*6, HCR*WWCC, and CDSN*5 are strongly associated with the pathogenesis of the disease.
Abstract: The PSORS1 locus in the major histocompatibility complex region is the major genetic determinant for psoriasis vulgaris. Within the PSORS1 region reside at least three potential candidate genes for psoriasis susceptibility. Specific allelic variants of the genes HLA-Cw*6, HCR*WWCC, and CDSN*5 are strongly associated with psoriasis vulgaris and are in strong linkage disequilibrium with each other. We have genotyped the three psoriasis vulgaris susceptibility alleles of the PSORS1 locus in two clinical variants of psoriasis (guttate psoriasis and palmoplantar pustulosis) to study whether PSORS1 is also involved in the pathogenesis of these variants. We also asked whether these two clinical subgroups could help us to distinguish the causative gene within the high-risk PSORS1 haplotype. The association of guttate psoriasis with the three PSORS1 susceptibility alleles was similar and even stronger than seen with psoriasis vulgaris. Palmoplantar pustulosis, however, did not show association with any of the three candidate genes at this locus. Finally, no correlation with the age of onset for disease was observed. Our results show conclusively that psoriasis vulgaris and guttate psoriasis have a similar genetic basis for their association to PSORS1, whereas palmoplantar pustulosis appears to be a distinct disorder.

207 citations

Journal ArticleDOI
TL;DR: Imipenem monotherapy or in combination with amikacin is well tolerated and demonstrates efficacy in severe disease refractory to sulfonamides, and sulfonamide combinations are effective for limited disease of relatively short duration.
Abstract: Background Actinomycetomas are chronic, granulomatous, subcutaneous infections caused by actinomycetes bacteria. Despite prolonged high-dose and combination antibiotic therapies, some cases remain resistant with risks of bone and visceral involvement. Objectives We sought to evaluate the efficacy and safety of imipenem monotherapy, and in combination with amikacin for the treatment of severe and refractory disease, and to identify the disease characteristics that might predict therapy failure with first-line sulfonamides. Methods A retrospective study was performed of all microbiologically confirmed cases of actinomycetomas treated since 1995 at a tertiary center for mycology. Eleven patients ( Nocardia , n = 10) were treated with sulfonamide combinations (trimethoprim/sulfamethoxazole and dapsone). Eight patients ( Nocardia , n = 7) refractory to previous therapies including sulfonamides received a 3-week course of either parenteral imipenem monotherapy (1.5 g daily, n = 3) or combination therapy with amikacin (1 g daily, n = 5), which was repeated at 6-month intervals. Results Eleven patients with limited disease and mean disease duration of 1.7 years responded successfully to sulfonamides after a mean treatment period of 15 months (range 6-48 months). Patients receiving imipenem had mean disease duration of 10 years, with visceral and bone involvement in 4 patients. Imipenem treatment was well tolerated, and 4 patients achieved clinical and microbiological cure after one to two courses of treatment, the others demonstrating greater than 75% clinical improvement and negative culture results. Limitations Patient cohorts in this study were small because strict criteria for inclusion included species identification and adequate follow-up periods. The efficacy data for imipenem ± amikacin therapy cannot be extrapolated to all Nocardia mycetomas, as the cohort treated in this study had particularly refractory infection. Conclusions Sulfonamides are effective for limited disease of relatively short duration. Imipenem monotherapy or in combination with amikacin is well tolerated and demonstrates efficacy in severe disease refractory to sulfonamides.

34 citations

Journal ArticleDOI
01 Aug 2003
TL;DR: This particular insertion mutation in the NOD2 gene does not appear to contribute to the genetic susceptibility of psoriasis vulgaris, PPP, palmo‐plantar pustular Psoriasis, guttate psOriasis and the control group.
Abstract: A C-insertion polymorphism in the NOD2 gene (3020insC) on chromosome 16 is a rare mutation associated with Crohn's disease. Crohn's disease and psoriasis are more commonly observed together than expected by chance. Furthermore a susceptibility locus for psoriasis has been identified on chromosome 16q which overlaps the recently identified susceptibility locus for Crohn's disease. Thus, NOD2 may potentially be important as a candidate susceptibility gene for psoriasis. We tested this hypothesis by genotyping psoriasis patients for the C-insertion polymorphism using the Taqman ABI 7700 sequencing system. No statistically significant differences were observed between psoriasis vulgaris (n = 216), palmo-plantar pustular psoriasis (PPP) (n = 100), guttate psoriasis (n = 118) and the control group (n = 283). In both patient and control groups, no mutant homozygotes were observed and approximately 4% were heterozygotes. This particular insertion mutation in the NOD2 gene does not appear to contribute to the genetic susceptibility of psoriasis vulgaris, PPP or guttate psoriasis. However, other mutations exist in the NOD2 gene, which may potentially have a role in psoriasis susceptibility.

33 citations


Cited by
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TL;DR: Anti-TNF strategies have three variants: a humanized chimeric anti–TNF- α monoclonal antibody, a fully human monocolonal anti-T NF- α antibody, and a human p75 TNF-receptor Fc fusion protein.

2,084 citations

Journal ArticleDOI
TL;DR: Comorbidities of psoriasis are attracting interest, and include impairment of quality of life and associated depressive illness, cardiovascular disease, and a seronegative arthritis known as psoriatic arthritis.

1,596 citations

Journal ArticleDOI
TL;DR: The epidemiology, clinical features, and impact on quality of life of psoriasis are reviewed.
Abstract: Psoriasis is a common chronic, recurrent, immune mediated disease of the skin and joints. It can have a significant negative impact on the physical, emotional, and, psychosocial wellbeing of affected patients. Psoriasis is found worldwide but the prevalence varies among different ethnic groups. It has a strong genetic component but environmental factors such as infections can play an important role in the presentation of disease. There are several clinical cutaneous manifestations of psoriasis but most commonly the disease presents as chronic, symmetrical, erythematous, scaling papules and plaques. The epidemiology, clinical features, and impact on quality of life of psoriasis are reviewed.

845 citations

Journal ArticleDOI
TL;DR: New evidence indicates that even some synonymous mutations are subject to constraint, often because they affect splicing and/or mRNA stability, which has implications for understanding disease, optimizing transgene design, detecting positive selection and estimating the mutation rate.
Abstract: Although the assumption of the neutral theory of molecular evolution - that some classes of mutation have too small an effect on fitness to be affected by natural selection - seems intuitively reasonable, over the past few decades the theory has been in retreat. At least in species with large populations, even synonymous mutations in exons are not neutral. By contrast, in mammals, neutrality of these mutations is still commonly assumed. However, new evidence indicates that even some synonymous mutations are subject to constraint, often because they affect splicing and/or mRNA stability. This has implications for understanding disease, optimizing transgene design, detecting positive selection and estimating the mutation rate.

819 citations

Journal ArticleDOI
TL;DR: Diagnosis of fungi infections is becoming more frequent because of expansion of at-risk populations and the use of treatment modalities that permit longer survival of patients, and techniques such as laser microdissection will be useful to detect the now more frequently recognized dual fungal infections and the local environment in which this phenomenon occurs.
Abstract: Summary: Fungal infections are becoming more frequent because of expansion of at-risk populations and the use of treatment modalities that permit longer survival of these patients. Because histopathologic examination of tissues detects fungal invasion of tissues and vessels as well as the host reaction to the fungus, it is and will remain an important tool to define the diagnostic significance of positive culture isolates or results from PCR testing. However, there are very few instances where the morphological characteristics of fungi are specific. Therefore, histopathologic diagnosis should be primarily descriptive of the fungus and should include the presence or absence of tissue invasion and the host reaction to the infection. The pathology report should also include a comment stating the most frequent fungi associated with that morphology as well as other possible fungi and parasites that should be considered in the differential diagnosis. Alternate techniques have been used to determine the specific agent present in the histopathologic specimen, including immunohistochemistry, in situ hybridization, and PCR. In addition, techniques such as laser microdissection will be useful to detect the now more frequently recognized dual fungal infections and the local environment in which this phenomenon occurs.

627 citations