ABSTRACT
Transient receptor potential canonical 4 (TRPC4) channel is a nonselective calcium-permeable cation channels. In intestinal smooth muscle cells, TRPC4 currents contribute more than 80% to muscarinic cationic current (mIcat). With its inward-rectifying current-voltage relationship and high calcium permeability, TRPC4 channels permit calcium influx once the channel is opened by muscarinic receptor stimulation. Polyamines are known to inhibit nonselective cation channels that mediate the generation of mIcat. Moreover, it is reported that TRPC4 channels are blocked by the intracellular spermine through electrostatic interaction with glutamate residues (E728, E729). Here, we investigated the correlation between the magnitude of channel inactivation by spermine and the magnitude of channel conductance. We also found additional spermine binding sites in TRPC4. We evaluated channel activity with electrophysiological recordings and revalidated structural significance based on Cryo-EM structure, which was resolved recently. We found that there is no correlation between magnitude of inhibitory action of spermine and magnitude of maximum current of the channel. In intracellular region, TRPC4 attracts spermine at channel periphery by reducing access resistance, and acidic residues contribute to blocking action of intracellular spermine; channel periphery, E649; cytosolic space, D629, D649, and E687.
Subject(s)
Amino Acids , Binding Sites , Calcium , Cytosol , Glutamic Acid , Myocytes, Smooth Muscle , Permeability , Polyamines , Receptors, Muscarinic , Spermine , Transient Receptor Potential ChannelsABSTRACT
Acute graft-versus-host disease (GVHD) is a common complication associated with bone marrow transplantation. In the rare cases where it occurs after solid organ transplantation, including that of the liver, pancreas, or heart, it often has fatal outcomes. A 50-year old man developed whole-body flaccid vesiculobullous eruption 6 weeks after living donor liver transplantation. Skin biopsy revealed epidermal necrosis with vacuolization of the basal layer and lymphocytic infiltration in the dermis. Stomach erosions were found during an endoscopy, and a concurrent biopsy revealed severe epithelial necrosis. GVHD was diagnosed, with mixed chimerism confirmed using short tandem repeat testing. Immunosuppressive agent therapy was instituted, but the patient expired from hematologic complications and brain damage 6 weeks after treatment initiation. Skin lesions in GVHD generally appear with erythematous maculopapular eruption, but some atypical cutaneous manifestations could be unnoticed by physicians. This report describes miliaria crystallina-like eruption of acute GVHD after liver transplantation.
ABSTRACT
No abstract available.
Subject(s)
Acupuncture , Foreign Bodies , Granuloma, Foreign-Body , Leprosy , Leprosy, LepromatousABSTRACT
Dermatofibroma is a fibrohistiocytic tumor of the skin that commonly occurs as a solitary lesion on the lower extremities of young women. Multiple eruptive dermatofibromas (MEDFs), defined as the presence of 5 to 8 dermatofibromas appearing within a period of 4 months, are rare, and the etiology of MEDFs remains unknown. However, MEDFs are frequently thought to be associated with altered immunity, such as autoimmune diseases and immunosuppression. It is unclear why MEDFs occur in association with these conditions, but this relationship may suggest that MEDFs are the result of an abortive immunoreactive process. We herein describe a middle-aged woman who developed multiple dermatofibroma. She had myasthenia gravis for 8 years, and developed MEDFs after undergoing oral corticosteroid treatment (245 mg/week) for 3 months. Therefore, our case suggests that the use of immunosuppressants is a more dominant factor for the development of MEDFs than underlying autoimmune diseases.
Subject(s)
Female , Humans , Autoimmune Diseases , Histiocytoma, Benign Fibrous , Immunosuppression Therapy , Immunosuppressive Agents , Lower Extremity , Myasthenia Gravis , SkinABSTRACT
BACKGROUND: Kaposi varicelliform eruption (KVE) is a disseminated viral infection primarily caused by the herpes simplex virus in the setting of an underlying chronic skin disease. Few studies have reported the clinical characteristics and predisposing factors for recurrent KVE.OBJECTIVES: To characterize the clinical features and predisposing factors for recurrent KVE.METHODS: This retrospective comparative study of recurrent vs. single-episode KVE was performed at the Pusan National University Hospital between 2004 and 2017.RESULTS: A total of 84 episodes occurred in 60 patients, and of these, 13 patients developed recurrence (21.7%). No statistically significant intergroup difference was observed in the mean age and sex distribution. The face was the most common site of involvement in both groups, followed by the trunk and the upper and lower extremities. Atopic dermatitis was the most common pre-existing disease in both groups; however, Darier's disease was more common in the recurrent KVE group, and this difference was statistically significant. Most patients with KVE (66.7%) showed aggravation of the underlying skin disease within 3 months of KVE onset. This finding was more prominent in patients with recurrent episodes (91.7%) than in those with single-episode KVE (58.3%), (p=0.040).CONCLUSION: This study can contribute to a better understanding of recurrent KVE and guide clinicians in treating patients with conditions predisposing to KVE.
Subject(s)
Humans , Causality , Darier Disease , Dermatitis, Atopic , Kaposi Varicelliform Eruption , Lower Extremity , Preexisting Condition Coverage , Recurrence , Retrospective Studies , Sex Distribution , Simplexvirus , Skin DiseasesABSTRACT
BACKGROUND: Secukinumab, a fully human monoclonal antibody that targets interleukin (IL)-17A, which is a central cytokine in the pathogenesis of psoriasis, has emerged as a promising treatment for moderate to severe psoriasis. However, to date, there are no real-world data for secukinumab in Korean patients with psoriasis. OBJECTIVE: To assess the clinical efficacy and safety of secukinumab in Korean patients with psoriasis. METHODS: Prospective data were gathered during follow-up from 28 consecutive patients with chronic plaque-type psoriasis treated with secukinumab for minimum of 12 weeks at a single referral center. Patient demographics, Psoriasis Area Severity Index (PASI) score, Physicians' Global Assessment (PGA), Dermatologic Life Quality Index (DLQI), and adverse events were investigated. RESULTS: The mean PASI score was significantly decreased after the induction period of secukinumab treatment (paired t-test, p<0.05). Of the 28 patients, 17 (60.7%) had obtained near complete clearance (PASI 90) at the last follow-up visit. No unexpected adverse events, other than nasopharyngitis, were observed. CONCLUSION: Secukinumab can be of benefit for the treatment of Korean patients with psoriasis, as the treatment was associated with a rapid and satisfactory response and safety profile.
Subject(s)
Humans , Demography , Follow-Up Studies , Interleukins , Korea , Nasopharyngitis , Prospective Studies , Psoriasis , Quality of Life , Referral and Consultation , Treatment OutcomeABSTRACT
Granuloma annulare is a benign granulomatous skin disease, clinically characterized by dermal papules tending to form annular shapes. Granuloma annulare is classified into localized, generalized, subcutaneous, and perforating types. Localized granuloma annulare is likely to resolve spontaneously, while generalized granuloma annulare usually takes a chronic course. Topical steroids, phototherapy, isotretinoin, dapsone, hydroxychloroquine, and other various treatments have been proposed, but some cases have been resistant to all of those treatment modalities. We experienced 3 cases of generalized granuloma annulare demonstrating a recalcitrant course that were successfully treated with methotrexate and propose that methotrexate may be an effective option for recalcitrant generalized granuloma annulare treatment.