RESUMEN
OBJECTIVE: To characterize long-term outcomes of PHACE syndrome. STUDY DESIGN: Multicenter study with cross-sectional interviews and chart review of individuals with definite PHACE syndrome ≥10 years of age. Data from charts were collected across multiple PHACE-related topics. Data not available in charts were collected from patients directly. Likert scales were used to assess the impact of specific findings. Patient-Reported Outcomes Measurement Information System (PROMIS) scales were used to assess quality of life domains. RESULTS: A total of 104/153 (68%) individuals contacted participated in the study at a median of 14 years of age (range 10-77 years). There were infantile hemangioma (IH) residua in 94.1%. Approximately one-half had received laser treatment for residual IH, and the majority (89.5%) of participants were satisfied or very satisfied with the appearance. Neurocognitive manifestations were common including headaches/migraines (72.1%), participant-reported learning differences (45.1%), and need for individualized education plans (39.4%). Cerebrovascular arteriopathy was present in 91.3%, with progression identified in 20/68 (29.4%) of those with available follow-up imaging reports. Among these, 6/68 (8.8%) developed moyamoya vasculopathy or progressive stenoocclusion, leading to isolated circulation at or above the level of the circle of Willis. Despite the prevalence of cerebrovascular arteriopathy, the proportion of those with ischemic stroke was low (2/104; 1.9%). PROMIS global health scores were lower than population norms by at least 1 SD. CONCLUSIONS: PHACE syndrome is associated with long-term, mild to severe morbidities including IH residua, headaches, learning differences, and progressive arteriopathy. Primary and specialty follow-up care is critical for PHACE patients into adulthood.
Asunto(s)
Coartación Aórtica , Anomalías del Ojo , Síndromes Neurocutáneos , Humanos , Lactante , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Síndromes Neurocutáneos/complicaciones , Anomalías del Ojo/complicaciones , Coartación Aórtica/complicaciones , Calidad de Vida , Estudios Transversales , CefaleaRESUMEN
OBJECTIVE: To examine the prevalence of preexisting articular bone pathology in patients with hip or knee pain due to osteoarthritis (OA) screened for fasinumab clinical trials. METHOD: This post-hoc analysis included patients with OA screened for three phase 3 fasinumab studies (NCT02683239, NCT03161093, NCT03304379). During screening, participants who met other clinical inclusion/exclusion criteria underwent radiography of knees, hips, and shoulders. Those with Kellgren-Lawrence grade (KLG) ≥ 2 for index joint and without an exclusionary finding proceeded to magnetic resonance imaging (MRI) of index, contralateral, and KLG ≥ 3 joints. Exclusionary findings included bone fragmentation/collapse, bone loss/resorption, osteonecrosis, and fracture, by either X-ray or MRI. Participants with extensive subchondral cysts were also excluded. Prevalence of abnormalities on radiographs and MRIs are reported. RESULTS: Of 27,633 participants screened, 21,997 proceeded to imaging. Of these, 1203 (5.5%) were excluded due to the presence of ≥ 1 joint with severe articular bone pathology (X-ray or MRI): bone fragmentation/collapse (2.60%), subchondral insufficiency fracture (SIF; 1.67%), osteonecrosis (1.11%), and significant bone loss (0.32%). Additionally, 3.13% screen-failed due to extensive subchondral cysts. More than half of the exclusions due to bone fragmentation/collapse (386/572), osteonecrosis (141/245) and significant bone loss (59/71), and approximately one third of SIF (133/367) and extensive subchondral cysts (229/689) were evident on X-rays. CONCLUSIONS: Approximately one in 20 participants with OA who met the clinical screening criteria for fasinumab phase 3 trials were later excluded due to preexisting severe articular bone pathology findings by X-ray or MRI.
RESUMEN
BACKGROUND: Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians. OBJECTIVE: To perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab. METHODS: A systematic review of the literature was performed, and an expert Delphi Panel was assembled. RESULTS: The available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective. CONCLUSION: Vaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Vacunas , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/tratamiento farmacológico , Consenso , Técnica Delphi , Dermatitis Atópica/tratamiento farmacológico , Vacunación/efectos adversos , Vacunas/efectos adversos , Vacunas/uso terapéuticoRESUMEN
The nummular phenotype of atopic dermatitis is clinically characterized by pruritic, coin-shaped plaques that are frequently recalcitrant to treatment. In this study, a retrospective chart review was conducted to evaluate the effectiveness and safety of dupilumab in children with nummular lesions of dermatitis. Twelve out of 14 patients demonstrated significant clinical improvement at a median time of 2.5 months (interquartile range, 1-4) after dupilumab initiation. A single case of paradoxical psoriasiform eruption was the only side effect reported in our cohort.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Dermatitis Atópica , Fenotipo , Humanos , Dermatitis Atópica/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Niño , Masculino , Estudios Retrospectivos , Femenino , Preescolar , Resultado del Tratamiento , AdolescenteRESUMEN
Urticaria in infants can cause significant anxiety in parents, especially if a trigger cannot be identified. In a retrospective study of 246 infants seen for urticaria of unknown etiology at Boston Children's Hospital, 88.2% had resolution of urticaria within 6 weeks. The etiology of urticaria was ultimately established in 62.6% (72/115) of acute urticaria and 12.5% (2/16) of chronic urticaria cases with follow-up data. Pediatric healthcare providers can counsel families that while etiology of urticaria is never determined in over 40% of infants, symptoms are most likely to resolve spontaneously.
Asunto(s)
Urticaria , Lactante , Niño , Humanos , Estudios Retrospectivos , Urticaria/diagnóstico , Urticaria/epidemiología , Urticaria/etiología , Ansiedad , Boston/epidemiología , Enfermedad CrónicaRESUMEN
BACKGROUND: Carpal tunnel syndrome (CTS), an entrapment neuropathy caused by pressure of the median nerve, is a progressive condition that can lead to a decreased quality of life. Studies suggest an association between CTS and arthritis; however, previous studies examining osteoarthritis (OA) and CTS are limited in number, scope and study design. This study estimated the incidence and risk of CTS among patients with OA, both overall and by specific joints, in a large population-based cohort in the United States. METHODS: Patients from the Optum claims database aged ≥ 45 years and diagnosed with OA between January 1, 2018, and December 31, 2022, were eligible for the OA cohort. The non-OA cohort included those without a diagnosis of OA at the index date and no history of OA for 12 months pre-index. Baseline characteristics were balanced using propensity score matching. The risk of CTS in the OA and non-OA cohort were evaluated using incidence rates and adjusted hazard ratios that were estimated using Cox regression. RESULTS: After applying the inclusion/exclusion criteria, 3,610,240 of the 6,023,384 adults with a diagnosis of OA remained in the OA cohort. After propensity-score matching, each cohort included 1,033,439 individuals. The incidence rates for CTS per 1000 person-years were 7.35 (95% confidence interval [CI] 7.21-7.49) in the OA cohort and 1.44 (95% CI 1.38-1.50) in the non-OA cohort. The risk of developing CTS in patients with OA was ~ 4 times that of patients without (hazard ratio = 3.80; 95% CI 3.54-4.07). This increased risk was found across all OA joint types, with OA of the hand/wrist having the highest risk for CTS. Additionally, multiple OA joints presented a higher risk compared with a single affected joint. CONCLUSIONS: OA increases the risk of CTS, but this is not limited to patients with hand/wrist OA, suggesting a systemic impact of OA on CTS. While the risk appears highest for patients with hand/wrist OA, patients with more distant affected joints like knee or hip also have an increased risk of CTS.
Asunto(s)
Síndrome del Túnel Carpiano , Osteoartritis , Humanos , Síndrome del Túnel Carpiano/epidemiología , Síndrome del Túnel Carpiano/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Estados Unidos/epidemiología , Anciano , Incidencia , Osteoartritis/epidemiología , Osteoartritis/diagnóstico , Factores de Riesgo , Bases de Datos Factuales , Osteoartritis de la Rodilla/epidemiología , Osteoartritis de la Rodilla/diagnóstico , Medición de Riesgo , Estudios RetrospectivosRESUMEN
PURPOSE: To provide a holistic and complete comparison of the five most advanced AI models in the augmentation of low-dose 18F-FDG PET data over the entire dose reduction spectrum. METHODS: In this multicenter study, five AI models were investigated for restoring low-count whole-body PET/MRI, covering convolutional benchmarks - U-Net, enhanced deep super-resolution network (EDSR), generative adversarial network (GAN) - and the most cutting-edge image reconstruction transformer models in computer vision to date - Swin transformer image restoration network (SwinIR) and EDSR-ViT (vision transformer). The models were evaluated against six groups of count levels representing the simulated 75%, 50%, 25%, 12.5%, 6.25%, and 1% (extremely ultra-low-count) of the clinical standard 3 MBq/kg 18F-FDG dose. The comparisons were performed upon two independent cohorts - (1) a primary cohort from Stanford University and (2) a cross-continental external validation cohort from Tübingen University - in order to ensure the findings are generalizable. A total of 476 original count and simulated low-count whole-body PET/MRI scans were incorporated into this analysis. RESULTS: For low-count PET restoration on the primary cohort, the mean structural similarity index (SSIM) scores for dose 6.25% were 0.898 (95% CI, 0.887-0.910) for EDSR, 0.893 (0.881-0.905) for EDSR-ViT, 0.873 (0.859-0.887) for GAN, 0.885 (0.873-0.898) for U-Net, and 0.910 (0.900-0.920) for SwinIR. In continuation, SwinIR and U-Net's performances were also discreetly evaluated at each simulated radiotracer dose levels. Using the primary Stanford cohort, the mean diagnostic image quality (DIQ; 5-point Likert scale) scores of SwinIR restoration were 5 (SD, 0) for dose 75%, 4.50 (0.535) for dose 50%, 3.75 (0.463) for dose 25%, 3.25 (0.463) for dose 12.5%, 4 (0.926) for dose 6.25%, and 2.5 (0.534) for dose 1%. CONCLUSION: Compared to low-count PET images, with near-to or nondiagnostic images at higher dose reduction levels (up to 6.25%), both SwinIR and U-Net significantly improve the diagnostic quality of PET images. A radiotracer dose reduction to 1% of the current clinical standard radiotracer dose is out of scope for current AI techniques.
Asunto(s)
Inteligencia Artificial , Fluorodesoxiglucosa F18 , Humanos , Reducción Gradual de Medicamentos , Tomografía de Emisión de Positrones/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: Pediatric oncology patients undergoing cancer treatment can often have numerous and recalcitrant cutaneous warts due to their underlying immunosuppression. There are little published data on the optimal management of warts in pediatric oncology patients undergoing active cancer treatment compared to patients having completed treatment. Our objective was to analyze the clinical course of warts treated within this patient population at Boston Children's Hospital over a 10-year period. METHODS: This was a single-institution retrospective study of 72 pediatric oncology patients from 1 September 2011 to 1 September 2021 who were treated for warts at Boston Children's Hospital. All patients had a diagnosis of cutaneous warts with at least one follow-up visit and were receiving active treatment for cancer either during or after concurrent treatment of their warts. We examined the modality and effectiveness of wart treatments while both on and offactive treatment of their cancer. RESULTS: The median age was 12 years (range 4-18). Fifty-four percent of patients were documented to have plantar warts. Sixty percent of patients with a documented number of warts had more than five warts at presentation. For cases in which outcomes were specified, treatment resulted in complete resolution of warts in only 24.0% of patients undergoing active cancer treatment compared to 63.3% of patients not on active treatment. Warts persisted or worsened in 56.0% of patients undergoing active cancer treatment compared to only 13.4% of patients not on active treatment. CONCLUSION: These data may help guide clinicians in evaluating and treating warts in pediatric oncology patients.
Asunto(s)
Verrugas , Niño , Humanos , Preescolar , Adolescente , Estudios Retrospectivos , Verrugas/tratamiento farmacológico , Administración Cutánea , Terapia de Inmunosupresión , Boston/epidemiología , Resultado del TratamientoRESUMEN
A better understanding of what skin conditions are most commonly diagnosed in different pediatric racial and ethnic groups in outpatient dermatology clinics could help guide the development of pediatric dermatology educational initiatives for primary care providers and general dermatologists who have limited access to pediatric dermatologists. Using a nationally representative dataset, we evaluated the most common diagnoses in patients younger than 15 years of age (children) and 15-24 years of age (youth) who present to outpatient dermatology clinics, stratified by race and ethnicity. While acne and dermatitis were among the top ten most common diagnoses in all racial and ethnic groups studied, Black children were also commonly diagnosed with dermatophytosis and impetigo, and Black and Hispanic children were often diagnosed with seborrheic dermatitis; pigmentary disorders were among the top three most common diagnoses in Black, Asian, and Hispanic youth. Training more physicians how to evaluate and treat common skin conditions in children and youth of diverse racial and ethnic backgrounds may improve access to care for skin disease in the United States.
Asunto(s)
Dermatología , Enfermedades de la Piel , Adolescente , Niño , Etnicidad , Humanos , Pacientes Ambulatorios , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/terapia , Estados UnidosRESUMEN
Porokeratosis ptychotropica is an unusual variant of porokeratosis characterized by papules and plaques located on the buttocks and gluteal cleft and showing multiple coronoid lamellae on histology. In this case report, we present the longitudinal clinical course of porokeratosis ptychotropica in a pediatric patient with individual red-brown hyperkeratotic lesions that enlarged and became confluent prior to surgical intervention. We also discuss the etiology of porokeratosis ptychotropica and review current as well as future treatment options for the disease.
Asunto(s)
Poroqueratosis/diagnóstico , Niño , Progresión de la Enfermedad , Humanos , Masculino , Poroqueratosis/etiología , Poroqueratosis/cirugíaRESUMEN
The formation of functional amyloid must be carefully regulated to prevent the accumulation of potentially toxic products. Premelanosome protein (PMEL) forms non-toxic functional amyloid fibrils that assemble into sheets upon which melanins ultimately are deposited within the melanosomes of pigment cells. PMEL is synthesized in the endoplasmic reticulum but forms amyloid only within post-Golgi melanosome precursors; thus, PMEL must traverse the secretory pathway in a non-amyloid form. Here, we identified two pre-amyloid PMEL intermediates that likely regulate the timing of fibril formation. Analyses by non-reducing SDS-PAGE, size exclusion chromatography, and sedimentation velocity revealed two native high Mr disulfide-bonded species that contain Golgi-modified forms of PMEL. These species correspond to disulfide bond-containing dimeric and monomeric PMEL isoforms that contain no other proteins as judged by two-dimensional PAGE of metabolically labeled/immunoprecipitated PMEL and by mass spectrometry of affinity-purified complexes. Metabolic pulse-chase analyses, small molecule inhibitor treatments, and evaluation of site-directed mutants suggest that the PMEL dimer forms around the time of endoplasmic reticulum exit and is resolved by disulfide bond rearrangement into a monomeric form within the late Golgi or a post-Golgi compartment. Mutagenesis of individual cysteine residues within the non-amyloid cysteine-rich Kringle-like domain stabilizes the disulfide-bonded dimer and impairs fibril formation as determined by electron microscopy. Our data show that the Kringle-like domain facilitates the resolution of disulfide-bonded PMEL dimers and promotes PMEL functional amyloid formation, thereby suggesting that PMEL dimers must be resolved to monomers to generate functional amyloid fibrils.
Asunto(s)
Amiloide/química , Modelos Moleculares , Cuerpos Multivesiculares/ultraestructura , Procesamiento Proteico-Postraduccional , Antígeno gp100 del Melanoma/química , Sustitución de Aminoácidos , Amiloide/metabolismo , Amiloide/ultraestructura , Línea Celular Tumoral , Cisteína/química , Cisteína/metabolismo , Cistina/química , Cistina/metabolismo , Dimerización , Retículo Endoplásmico/enzimología , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/ultraestructura , Aparato de Golgi/enzimología , Aparato de Golgi/metabolismo , Aparato de Golgi/ultraestructura , Proteínas Fluorescentes Verdes/química , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Kringles , Microscopía Electrónica de Transmisión , Peso Molecular , Cuerpos Multivesiculares/química , Cuerpos Multivesiculares/metabolismo , Mutagénesis Sitio-Dirigida , Mutación Puntual , Pliegue de Proteína , Estabilidad Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Antígeno gp100 del Melanoma/genética , Antígeno gp100 del Melanoma/metabolismoRESUMEN
Cutaneous small-vessel vasculitis (CSVV) is an infrequent manifestation of pediatric inflammatory bowel disease (IBD). We report two cases of CSVV associated with ulcerative colitis, review the literature, and discuss the diagnostic evaluation of children who present with CSVV and abdominal pain. After excluding more common causes of CSVV and abdominal pain in children, including immunoglobulin A vasculitis (previously Henoch-Schönlein purpura), infectious colitis, and drug-induced vasculitis, alternative diagnoses such as CSVV secondary to IBD or systemic vasculitis with gastrointestinal involvement must be considered.
Asunto(s)
Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Cutáneas Vasculares/diagnóstico , Vasculitis/diagnóstico , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Piel/patología , Enfermedades Cutáneas Vasculares/complicaciones , Vasculitis/complicacionesRESUMEN
The formation of a dynamic, actin-rich immunological synapse (IS) and the polarization of cytolytic granules toward target cells are essential to the cytotoxic function of NK cells. Following polarization, lytic granules navigate through the pervasive actin network at the IS to degranulate and secrete their toxic contents onto target cells. We examined lytic granule motility and persistence at the cell cortex of activated human NK cells, using high-resolution total internal reflection microscopy and highly quantitative analysis techniques. We illustrate that lytic granules are dynamic and observe substantial motility at the plane of the cell cortex prior to, but not after, degranulation. We also show that there is no significant change in granule motility in the presence of Latrunculin A (which induces actin depolymerization), when added after granule polarization, but that there is a significant decrease in lytic granule persistence subsequent to degranulation. Thus, we show that lytic granules are highly dynamic at the cytolytic human NK cell IS prior to degranulation and that the persistence of granules at the cortex following exocytosis requires the integrity of the synaptic actin network.
Asunto(s)
Actinas/inmunología , Degranulación de la Célula/inmunología , Sinapsis Inmunológicas/inmunología , Células Asesinas Naturales/inmunología , Vesículas Secretoras/inmunología , Actinas/metabolismo , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Degranulación de la Célula/efectos de los fármacos , Línea Celular , Humanos , Sinapsis Inmunológicas/metabolismo , Células Asesinas Naturales/citología , Células Asesinas Naturales/metabolismo , Vesículas Secretoras/metabolismo , Tiazolidinas/farmacologíaRESUMEN
Human epidermal melanocytes play a central role in sensing the environment and protecting the skin from the drastic effects of solar ultraviolet radiation and other environmental toxins or inflammatory agents. Melanocytes survive in the epidermis for decades, which subjects them to chronic environmental insults. Melanocytes have a poor self-renewal capacity; therefore, it is critical to ensure their survival with genomic stability. The function and survival of melanocytes is regulated by an elaborate network of paracrine factors synthesized mainly by epidermal keratinocytes and dermal fibroblasts. A symbiotic relationship exists between epidermal melanocytes and keratinocytes on the one hand, and between melanocytes and dermal fibroblasts on the other hand. Melanocytes protect epidermal keratinocytes and dermal fibroblasts from the damaging effects of solar radiation, and the latter cells synthesize biochemical mediators that maintain the homeostasis, and regulate the stress response of melanocytes. Disruption of the paracrine network results in pigmentary disorders, due to abnormal regulation of melanin synthesis, and compromise of melanocyte survival or genomic stability. This review provides an update of the current knowledge of keratinocyte- and fibroblast-derived paracrine factors and their contribution to melanocyte physiology, and how their abnormal production is involved in the pathogenesis of common pigmentary disorders.
Asunto(s)
Fibroblastos/metabolismo , Homeostasis , Queratinocitos/metabolismo , Melanocitos/metabolismo , Trastornos de la Pigmentación/patología , Rayos Ultravioleta , Animales , Fibroblastos/efectos de la radiación , Homeostasis/efectos de la radiación , Humanos , Queratinocitos/efectos de la radiación , Melanocitos/efectos de la radiaciónRESUMEN
Vitiligo is the most common acquired pigmentary disorder, which afflicts 0.5%-1% of the world population, and is characterized by depigmented skin patches resulting from melanocyte loss. Vitiligo has a complex etiology and varies in its manifestations, progression, and response to treatment. It presents as an autoimmune disease, evidenced by circulating melanocyte-specific antibodies, and association with other autoimmune diseases. However, autoimmunity may be secondary to the high oxidative stress in vitiligo skin and to intrinsic defects in melanocytes and their microenvironment, which contribute to aberrant stress response, neo-antigenicity, and susceptibility of melanocytes to immune attack and apoptosis. There is also a genetic predisposition to vitiligo, which sensitizes melanocytes to environmental agents, such as phenolic compounds. Currently, there are different treatment modalities for re-pigmenting vitiligo skin. However, when repigmentation is achieved, the major challenge is maintaining the pigmentation, which is lost in 40% of cases. In this review, we present an overview of the clinical aspects of vitiligo, its pathophysiology, the intrinsic defects in melanocytes and their microenvironment, and treatment strategies. Based on lessons from the biology of human melanocytes, we present our perspective of how repigmentation of vitiligo skin can be achieved and sustained.
Asunto(s)
Vitíligo/fisiopatología , Vitíligo/terapia , Autoinmunidad , Microambiente Celular , Humanos , Melanocitos/patología , Estrés Oxidativo , Vitíligo/inmunologíaRESUMEN
SLC45A2 encodes a putative transporter expressed primarily in pigment cells. SLC45A2 mutations cause oculocutaneous albinism type 4 (OCA4) and polymorphisms are associated with pigmentation variation, but the localization, function, and regulation of SLC45A2 and its variants remain unknown. We show that SLC45A2 localizes to a cohort of mature melanosomes that only partially overlaps with the cohort expressing the chloride channel OCA2. SLC45A2 expressed ectopically in HeLa cells localizes to lysosomes and raises lysosomal pH, suggesting that in melanocytes SLC45A2 expression, like OCA2 expression, results in the deacidification of maturing melanosomes to support melanin synthesis. Interestingly, OCA2 overexpression compensates for loss of SLC45A2 expression in pigmentation. Analyses of SLC45A2- and OCA2-deficient mouse melanocytes show that SLC45A2 likely functions later during melanosome maturation than OCA2. Moreover, the light skin-associated SLC45A2 allelic F374 variant restores only moderate pigmentation to SLC45A2-deficient melanocytes due to rapid proteasome-dependent degradation resulting in lower protein expression levels in melanosomes than the dark skin-associated allelic L374 variant. Our data suggest that SLC45A2 maintains melanosome neutralization that is initially orchestrated by transient OCA2 activity to support melanization at late stages of melanosome maturation, and that a common allelic variant imparts reduced activity due to protein instability.
Asunto(s)
Antígenos de Neoplasias/metabolismo , Melanocitos/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Pigmentación de la Piel/fisiología , Animales , Antígenos de Neoplasias/fisiología , Proteínas Portadoras/metabolismo , Línea Celular , Canales de Cloruro/metabolismo , Células HeLa , Humanos , Lisosomas/metabolismo , Masculino , Melanosomas/metabolismo , Proteínas de Transporte de Membrana/fisiología , Ratones , Pigmentación/fisiología , Estabilidad Proteica , Piel/metabolismoAsunto(s)
Dermatitis Atópica , Medicaid , Humanos , Estados Unidos , Dermatitis Atópica/economía , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/terapia , Medicaid/economía , Cobertura del Seguro/economía , Cobertura del Seguro/estadística & datos numéricos , Administración Tópica , Antiinflamatorios no Esteroideos/economía , Antiinflamatorios no Esteroideos/uso terapéutico , Antiinflamatorios no Esteroideos/administración & dosificaciónRESUMEN
A Nepalese heterozygous carrier of a CCR5 mutant, designated 118delF, was characterized. There was a 3 basepair deletion at 352-354 in the CCR5 open reading frame, resulting in the deletion of the phe-118 residue located in the third transmembrane domain. The mutant protein has retained antigen specificity near the third extra-cellular loop (ECL3), but that of ECL2 is markedly reduced. The mutation has also abrogated HIV co-receptor activity. Clinically, the HIV disease had progressed slowly.