46 research outputs found

    Plasma exosome miR-155-5p as an independent prognostic risk factor for Mycosis Fungoides

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    Introduction: Mycosis Fungoides (MF) is a rare non-Hodgkin Lymphoma with variable progression that comprises half of all cutaneous T-cell lymphomas (CTCLs). Previous studies have shown higher expression of the micro-RNA miR-155-5p isolated from biopsies of MF tumors compared to early-stage lesions and healthy skin, illustrating the potential for miR-155-5p to serve as a prognostic indicator. Small extracellular vesicles (30-150 nm) called exosomes are known to play a role in cancer signaling and progression by carrying micro-RNAs. However, no studies have measured circulating exosomal miR-155-5p in the blood of patients with MF. We hypothesize that miR-155-5p is expressed higher in plasma exosomes of patients with MF compared to healthy volunteers. Methods: 6 patients with a diagnosis of MF and 9 healthy patients at Jefferson Dermatology Associates were enrolled in the study. Phlebotomy samples were obtained and plasma isolated by centrifugation. Exosomes were extracted by ExoQuick reagent and size confirmed by NanoSight software. RNA was extracted and qRT-PCR performed with Taqman probes for miR-155-5p and miR-103 (control). Delta-delta CT analysis was performed to analyze expression. Results: Analysis of three PCR runs determined the control (miR-103) to be expressed differently across samples with poor amplification. Additionally, miR-155-5p was variably expressed in the samples extracted from healthy volunteers. No pattern is discernible. Discussion: Given that sample volume is a proxy for pre-reaction cDNA in each sample, adaptation of the protocol and a new control is needed to more accurately measure miRNA expression. No conclusions can be made at this time

    Role of signalling molecules in the developing avian wing

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    The aim of this study was to investigate the role of signalling molecules during the development of the chick limb. First, it was demonstrated that a functional gradient of bioactive FGFs is present down the limb from distal to proximal. This functional FGF gradient decreased at stage 26, at the time of AER regression. Although morphogenetic gradients are of considerable theoretical importance in developmental biology, there are rather few practical demonstrations of their existence. The effects of prolonging the presence of active FGF on limb pattern formation were investigated. Application of ectopic FGF-4 to the distal tip of the limb at stage 26 had a number of effects on limb development. In particular, the cartilage structure conventionally labelled element "5" increased in size and in some instances acquired a digit-like morphology. The evolutionary considerations of this finding are briefly considered. Analysis, including 3D computer reconstruction, of the musculature and vasculature of limbs after FGF implants was carried out in the hope of establishing the identity of this digit like element. This proved not to be possible. However, both muscle mass and vascularisation had increased after the procedure. Known molecular pathways involving the proximo-distal patterning of the limb were then investigated. Whole mount in situ hybridisation studies were carried out with respect to FGF-4, sonic hedgehog, Hoxd-11 and FGF-8. These revealed that the shh/ FGF positive feedback loop was not involved in these changes. FGF-8 expression in late stage AERs was markedly increased. Hoxd-11 expression was not affected by ectopic FGF implants. Together, these findings suggest that the effect of FGF implants is mediated by a novel mechanism. The effect of FGF-4 implants on programmed cell death in the limb was examined. At stage 28 anterior necrotic zone was larger, and had shifted distally. However, the posterior necrotic zone was absent. The implications of these findings for limb development were discussed

    Comparative personality traits of temperament and character, psychopathology, and onset age of smoking in predicting opiate dependence

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    Introduction: According to drug gateway theory, smoking cigarette, especially, low onset age of smoking, is one of the risk factors for future use. The present study deals with comparison of nicotine addicts and opiate addicts in order to identify that what differences in personality traits and onset age of smoking exist in these two groups that cause some individuals to appeal to other substances after starting to use cigarette. Methods: Two groups of opiate addicts and nicotine addicts were randomly selected. Revised version of Cloninger’s Temperament Inventory Questionnaire, Fagrastrom’s Nicotine Dependence and Maudsley’s Addiction Profile were used. The study length was 10 month. ANOVA and logistic regression were applied for data analysis.  Results: Opiate addicts had higher scores in novelty seeking dimension and lower scores in cooperativeness (P= 0/001), compared to nicotine addicts. The onset age of smoking cigarette in opiate addicts was lower than nicotine addicts.  Conclusion: Low onset age of smoking cigarette, high novelty seeking and low cooperativeness in opiate dependents are among the important personality traits in future use of drugs that can predict the subsequent start of using opiate drugs.  Declaration of Interest: None

    Chlormethine Gel for Patients with Mycosis Fungoides Cutaneous T Cell Lymphoma: A Review of Efficacy and Safety in Clinical Trial and Real-World Settings

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    Mycosis fungoides (MF) is a rare disease and is the most common form of cutaneous T cell lymphoma. Topical chlormethine (CL) gel is the first cytotoxic chemotherapy gel that was specifically developed for treatment of MF. In this review, we provide an overview of all available data on the use of CL gel for treatment of patients with MF. On the basis of the current data collected, CL gel is highly effective, with good response rates observed both in clinical trial and real-world settings. While the gel is approved for monotherapy, it is also used in combination with concomitant skin-directed or systemic therapies in clinical practice. Responses to CL gel treatment can be rapid, but they also frequently occur with a delayed onset of up to 6 months. This indicates that continued treatment with CL gel is important. CL gel has a manageable safety profile, with most adverse events being mild and skin related. Contact dermatitis is one of the more common skin-related adverse events to occur with CL gel treatment that can potentially lead to treatment discontinuation. The data from the literature indicate that patients being treated with CL gel should be monitored carefully, and that dermatitis must be managed effectively to allow patients to continue treatment and achieve the best possible response to treatment

    The Role of Toll-Like Receptor 4 in the Progression of Keloids

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    Keloids are highly prevalent in the population and their pathogenesis is largely unknown. T-cell lymphoma research shows that toll like receptor-4 (TLR-4) is highly expressed on CD206+ immunosuppressive macrophages and is implicated in maintaining the tumor microenvironment. Additionally, fibronectin, specifically extra domain A (EDA), is highly expressed and is associated with immunosuppression via the TLR-4 pathway. Assuming that keloids mimic the tumor microenvironment, we hypothesize that TLR-4 is implicated in the pathogenesis of keloids. Using keloid tissue samples and normal breast tissue as a control, immunohistochemistry was performed to observe the presence and co-localization of these markers. Three antibodies were used to examine co-localization of CD-206 with TLR-4 and CD-206 with EDA to determine if these three components were localized to the same region in the keloid tissue. The secondary antibodies were immunofluorescent, and the tissue was analyzed using electron microscopy. Upon analysis, it was found that in keloid tissue CD-206 and TLR-4 were co-localized. To further support the hypothesis, it was found that CD-206 and EDA were also co-localized. In the control group, there was no evidence of co-localization of CD-206 with TLR-4 or with EDA. These findings support the overall hypothesis that TLR-4 is involved in the pathogenesis of keloids. Discovering that CD-206 co-localizes with both TLR-4 and EDA indicates that these three molecules interact to help form the tumor microenvironment needed to support keloid formation. Knowing this information, studies can begin to look into possible immunological targets for keloid treatment that access this immunosuppressive pathway

    Extreme Peripheral Blood Plasmacytosis Mimicking Plasma Cell Leukemia as a Presenting Feature of Angioimmunoblastic T-Cell Lymphoma (AITL).

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    Angioimmunoblastic T-cell lymphoma (AITL) is one of four major subtypes of nodal peripheral T cell lymphoma, characterized by its cell of origin, the follicular helper T-cell (TFH). Patients typically present with prominent constitutional (B) symptoms, generalized lymphadenopathy, hepatosplenomegaly, cytopenias, and rash. Here we present a case of a 62-year-old male with progressive cervical adenopathy, fevers and weight loss presenting with extreme polyclonal plasmacytosis and high plasma EBV viral load. While the initial presentation appeared to mimic plasma cell leukemia or severe infection, lymph node biopsy and bone marrow biopsy confirmed a diagnosis of AITL. This case highlights the heterogeneity of the clinical presentation of AITL to enable physicians to more promptly recognize, diagnose and initiate treatment

    Assessment of Treatment Response of Keloid Patients

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    Introduction: Keloids are benign exophytic scars ranging from asymptomatic, small papules to large symptomatic plaques that affect patients’ quality of life. The most effective treatment for this troublesome condition has yet to be determined. This study aims to demonstrate that intralesional Kenalog injections produce better keloid outcomes than surgical excision. Methods: Researchers called 504 Jefferson keloid patients to determine their keloid outcomes post-treatment. Patients were asked to confirm their last treatment method, describe the percent change in size of their lesion(s), and rate their symptoms (pruritis and pain) on a scale of 0-10 before and after treatment. Excision and Kenalog group outcomes were compared using t-tests. Results: 84 patients with 114 keloids responded to the survey. Of these keloids, 16 were excised and 90 were treated with Kenalog. While excised keloids and Kenalog-injected keloids comparably produced some decrease in size (81% vs. 77%), more excised keloids resolved completely (37% vs. 10%) and more Kenalog-treated keloids decreased less than 50% in size (41% vs. 19%). However, the excision group also showed more cases of increased keloid size (13% vs. 4%). Comparison of symptom scores showed no significant difference in pruritus scores (p = 0.156), but demonstrated that excisions reduced pain scores significantly (p = 0.009). Discussion: The results of this study suggest that excised keloids produce better size and pain reduction than Kenalog-injected keloids. However, outcome analysis was limited by the survey responses collected, as consenting patients mainly received Kenalog treatments. Thus, further research is necessary to accurately determine which treatment modality is most effective

    The Impact of Patient Characteristics on Quality of Life in Keloid Patients

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    Introduction: Quality of life (QoL) is an important metric in assessing dermatological diseases such as keloids. This study evaluated the effects of patient characteristics on QoL in keloid patients. Methods: This was a cross-sectional study. 36 patients presenting to the keloid clinic at TJUH were surveyed. QoL subscale scores for emotion, symptom, and function were calculated in addition to a total score for each patient using a keloid-specific questionnaire. The association between the QoL scores and patient characteristics of sex, ethnicity, as well as keloid location, duration, visibility, size, number, pain score, and pruritis score were evaluated using t-tests. Results: Significant differences in QoL were observed in relation to visibility, size, location, pain, and pruritis. QoL was worse in patients with non-visible compared to visible keloids (p=0.001). Patients with large keloids had worse quality of life than those with small keloids (p=0.002) or medium keloids (p=0.015). Patient with ear keloids reported better QoL (p=0.001) while patients with chest keloids reported worse QoL (p=0.014). Patients who reported mild pain scores had better quality of life than those who reported moderate (p=0.001) or severe pain scores (p=0.003). Patients who reported severe pruritis scores had worse quality of life than those who reported mild (p=0.002) or moderate scores (p=0.003). Discussion: QoL in keloid patients was significantly impacted by multiple patient characteristics. The relationship between QoL scores and the size, pain score, and pruritis score of keloids emphasizes the need for effective keloid treatments to improve QoL in keloid patients
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