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Journal of the American Academy of... Jan 2022Itch pathogenesis is broadly characterized into histaminergic and nonhistaminergic pathways and transmitted via 2 main receptor families: G protein-coupled receptors and... (Review)
Review
Itch pathogenesis is broadly characterized into histaminergic and nonhistaminergic pathways and transmitted via 2 main receptor families: G protein-coupled receptors and transient receptor potential channels. In the skin, itch is primarily transmitted by unmyelinated type C and thinly myelinated type Aδ nerve fibers. Crosstalk between the immune and neural systems modulates itch transmission at the skin, spinal cord, and brain. Among the many known pruritogens, Th2 cytokines, such as interleukin-4, interleukin-13, interleukin-31, and thymic stromal lymphopoietin, are particularly important mediators that signal through shared Janus kinase pathways, representing novel targets for novel itch therapeutics. Emerging evidence has also revealed that the opioidergic system is a potent modulator of itch transmission, with increased μ-opioid activity and decreased κ-opioid activity contributing to itch pathogenesis. Optimal management of itch requires that treatment approaches be tailored to specific etiologic itch subtypes. When the etiology is unknown and patients are given a diagnosis of chronic pruritus of unknown origin, treatment should be guided by the presence of Th2 polarization, often reflected by increased blood eosinophils. In the second article of this 2-part series, we outline our current understanding of itch pathogenesis and discuss available and emerging treatments for itch.
Topics: Analgesics, Opioid; Humans; Pruritus; Skin
PubMed: 34648873
DOI: 10.1016/j.jaad.2021.07.078 -
European Journal of Pediatrics Aug 2014Thymus is essential for immunity as it provides environment for T cell differentiation and maturation. There is limited information on various factors which determine... (Observational Study)
Observational Study
UNLABELLED
Thymus is essential for immunity as it provides environment for T cell differentiation and maturation. There is limited information on various factors which determine thymic size at birth. We studied the influence of cord blood zinc and copper levels and maternal and neonatal nutritional status on thymic size in term low-birth-weight (LBW) newborns. A prospective observational study on 44 term LBW (<2,500 g) newborns (cases) and 71 gestational age-matched newborns weighing ≥2,500 g (controls). Sonographically determined thymic index was correlated to cord blood zinc and copper levels and maternal and neonatal nutritional status. Thymic index measured 3.74 ± 1.57 cm(3) in LBW newborns compared to 4.90 ± 2.33 cm(3) in normal-birth-weight newborns. Thymic index was significantly correlated to cord blood zinc levels but not to cord blood copper levels and had linear relationship to the maternal body mass index and midarm circumference and neonatal anthropometric parameters.
CONCLUSION
Thymic index is linearly related to cord blood zinc levels and maternal and neonatal nutritional status. Compared to thymic size in the Western newborns, the thymus is less than half in size in Indian newborns of normal birth weight. Reduced thymic size in Indian newborns in general and LBW infants in particular may have consequences for their immune competence and the risk of infections. Improving nutrition of pregnant women, particularly zinc nutriture might favorably influence thymic size in their offspring.
Topics: Adult; Anthropometry; Copper; Female; Fetal Blood; Gestational Age; Humans; India; Infant, Low Birth Weight; Infant, Newborn; Male; Nutritional Status; Pregnancy; Prospective Studies; Thymus Gland; Ultrasonography; Zinc
PubMed: 24647797
DOI: 10.1007/s00431-014-2293-7 -
General Thoracic and Cardiovascular... May 2019We report the first known case of a metastatic thymic tumor arising from spermatic cord leiomyosarcoma, occurring in a 35-year-old man. He had undergone an orchiectomy...
We report the first known case of a metastatic thymic tumor arising from spermatic cord leiomyosarcoma, occurring in a 35-year-old man. He had undergone an orchiectomy 24 months previously and a surgical excision of a subcutaneous metastasis 4 months prior to his current presentation. Computed tomography revealed a 1.5-cm, round-shaped anterior mediastinal mass. A thymectomy was performed and the diagnosis of metastatic leiomyosarcoma was made.
Topics: Adult; Genital Neoplasms, Male; Humans; Leiomyosarcoma; Male; Orchiectomy; Spermatic Cord; Thymectomy; Thymus Neoplasms; Tomography, X-Ray Computed
PubMed: 30032446
DOI: 10.1007/s11748-018-0973-3 -
World Journal of Clinical Cases Jan 2023Thymic lipofibroadenomas are extremely rare. In this study, we investigated the clinicopathological characteristics of thymic lipofibroadenomas.
BACKGROUND
Thymic lipofibroadenomas are extremely rare. In this study, we investigated the clinicopathological characteristics of thymic lipofibroadenomas.
CASE SUMMARY
This study included three patients with thymic lipofibroadenomas. We retrospectively analyzed the patient data to determine the clinicopathological characteristics of thymic lipofibroadenomas. The study included one man and two women [mean age, 43 (33-59) years]. All patients were non-smokers and presented with well-defined anterior mediastinal tumors. The cut surfaces of the tumors were solid, with a mixture of yellow and white areas. Microscopic evaluation of resected specimens showed scattered cord-like structures of epithelial cells embedded within abundant fibrotic and hyaline stroma admixed with variable quantities of adipose tissue. One patient showed hyperplastic thymic tissue in a part of the tumor.
CONCLUSION
Thymic lipofibroadenomas are an extremely rare type of benign thymic tumor. Surgical removal of lipofibroadenomas is usually curative.
PubMed: 36687181
DOI: 10.12998/wjcc.v11.i1.164 -
Pediatric Allergy and Immunology :... Mar 2015The fetal immune system is a critical window of development. The epithelial cell-derived cytokines, thymic stromal lymphopoietin (TSLP), and interleukin-33 (IL-33) have...
BACKGROUND
The fetal immune system is a critical window of development. The epithelial cell-derived cytokines, thymic stromal lymphopoietin (TSLP), and interleukin-33 (IL-33) have received attention for their role in allergic responses but not been studied during this critical window. The objectives were to assess correlations among IL-33, TSLP, and IgE in umbilical cord blood samples and identify prenatal predictors of these biomarkers.
METHODS
This study utilized data and banked cord blood collected in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada cohort study of 2001 pregnant women. Our analytic sample comprised the 1254 women with a singleton, term birth with a cord blood sample. Spearman correlation coefficients (SCC) and logistic regression models were used to examine associations between biomarkers and identify potential predictors of elevated biomarker levels.
RESULTS
Thymic stromal lymphopoietin and IL-33 were more strongly correlated with each other (SCC = 0.75, p < 0.0001) than with IgE (IL-33 SCC = 0.14, TSLP SCC = 0.21). Maternal allergy, heavy street traffic, and elevated birth weight were significantly associated with jointly elevated TSLP and IL-33 levels, whereas maternal age and female infant sex were inversely associated with elevated IgE.
CONCLUSIONS
In this population of Canadian women and infants, TSLP and IL-33 were detectable in cord blood, more strongly correlated with each other than with IgE, and associated with maternal characteristics indicative of inflammatory responses. This study motivates investigation into the value of cord blood IL-33 and TSLP levels as childhood allergy predictors and raises interesting questions regarding in utero coordinated regulation of these cytokines.
Topics: Adult; Birth Weight; Cytokines; Environmental Exposure; Enzyme-Linked Immunosorbent Assay; Female; Fetal Blood; Humans; Hypersensitivity; Interleukin-33; Mothers; Pregnancy; Young Adult; Thymic Stromal Lymphopoietin
PubMed: 25620084
DOI: 10.1111/pai.12340 -
Cytotherapy Jun 2015Umbilical cord blood (UCB) is now widely used as an alternative hematopoietic stem cell source for patients lacking closely matched related or unrelated adult donors.... (Review)
Review
Umbilical cord blood (UCB) is now widely used as an alternative hematopoietic stem cell source for patients lacking closely matched related or unrelated adult donors. UCB transplantation has traditionally been associated with delayed engraftment, poor immune reconstitution and consequent increased risk of infection. More recent clinical studies, however, suggest that conditioning regimens and in particular the omission of in vivo T-cell depletion may play a crucial role in post-transplant T-cell expansion, facilitating a uniquely rapid immune recovery after UCB transplantation. The peculiar characteristics of UCB cells, the importance of thymic function and the role of conditioning regimens and graft-versus-host disease influencing immune reconstitution are described. The last part of the review reports available data on UCB, as well as third-party peripheral blood derived anti-viral cell therapy, which provides a novel approach to rescue UCB recipients with viral complications in the post-transplant period.
Topics: Cord Blood Stem Cell Transplantation; Cytokines; Fetal Blood; Humans; T-Lymphocytes, Cytotoxic
PubMed: 25946726
DOI: 10.1016/j.jcyt.2015.03.614 -
Frontiers in Immunology 2020T cell-mediated immune tolerance is a state of unresponsiveness of T cells towards specific self or non-self antigens. This is particularly essential during... (Review)
Review
T cell-mediated immune tolerance is a state of unresponsiveness of T cells towards specific self or non-self antigens. This is particularly essential during prenatal/neonatal period when T cells are exposed to dramatically changing environment and required to avoid rejection of maternal antigens, limit autoimmune responses, tolerate inert environmental and food antigens and antigens from non-harmful commensal microorganisms, promote maturation of mucosal barrier function, yet mount an appropriate response to pathogenic microorganisms. The cell-intrinsic and cell extrinsic mechanisms promote the generation of prenatal/neonatal T cells with distinct features to meet the complex and dynamic need of tolerance during this period. Reduced exposure or impaired tolerance in early life may have significant impact on allergic or autoimmune diseases in adult life. The uniqueness of conventional and regulatory T cells in human umbilical cord blood (UCB) may also provide certain advantages in UCB transplantation for hematological disorders.
Topics: Age Factors; Animals; Cord Blood Stem Cell Transplantation; Humans; Immune Tolerance; Infant; Infant, Newborn; Phenotype; Receptors, Antigen, T-Cell; Self Tolerance; T-Lymphocytes; Thymus Gland; Transplantation, Homologous; Umbilical Cord
PubMed: 33329542
DOI: 10.3389/fimmu.2020.576261 -
Cytotherapy 2007Over the past years unrelated cord blood transplant (UCBT) has emerged as an effective alternative to unrelated donor blood and marrow transplantation. However, despite... (Review)
Review
Over the past years unrelated cord blood transplant (UCBT) has emerged as an effective alternative to unrelated donor blood and marrow transplantation. However, despite several advantages, its success is limited by the high incidence of opportunistic infections (OI), most of which are viral. Infection-related mortality is the primary cause of death after UCBT with most deaths occurring in the first 3-6 months post transplant. For several months, until recovery of the thymus is restored to support de novo T cell generation, protective antiviral immunity depends on the activity of post-thymic T cells infused within the cord blood (CB) grafts. However, almost all CB T cells are antigen inexperienced (naïve) lymphocytes that have been functionally altered by placental factors to protect pregnancy. CB T cells need to undergo in vivo priming, Th1/Tc1 maturation, and peripheral expansion before they can afford immunologic protection. This article provides an overview of what is currently known regarding the reconstitution of adaptive immunity following UCBT including our own data from prospective analyses of pediatric cohorts. Remarkable immunophenotypic changes are notable already in the first 2-3 weeks post-UCBT. These changes result from apparent 'homeostatic' peripheral T cell expansion in the lymphopenic environment. While we can identify patient- and graft-specific predictive factors, the concordant emergence of T cell subsets displaying the phenotype of Th1/Tc1 cytotoxic effector cells can be statistically linked to those UCBT recipients who will subsequently develop viral and other opportunistic infections. Antigen presenting dendritic cell reconstitution may also reflect alterations in immunocompetence due to OI and/or GVHD.
Topics: Cord Blood Stem Cell Transplantation; Fetal Blood; Flow Cytometry; Humans; Lymphocyte Activation; T-Lymphocytes; Time Factors
PubMed: 17453963
DOI: 10.1080/14653240701231014 -
Frontiers in Immunology 2018Mice engrafted with human immune cells offer powerful model systems to investigate molecular and cellular processes of tumorigenesis, as well as to test therapeutic... (Review)
Review
Mice engrafted with human immune cells offer powerful model systems to investigate molecular and cellular processes of tumorigenesis, as well as to test therapeutic approaches to treat the resulting cancer. The use of umbilical cord blood mononuclear cells as a source of human immune cells for engraftment is technically straightforward, and provides T lymphocytes and autologous antigen-presenting cells (including B cells, monocytes, and DCs) that bear cognate antigen presenting molecules. By using a human-specific oncogenic virus, such as Epstein-Barr virus, neoplastic transformation of the human B cells can be induced in a manner that models progressive stages of tumorigenesis from nascent neoplasia to the establishment of vascularized tumor masses with an immunosuppressive environment. Moreover, since tumorigenesis occurs in the presence of autologous T cells, this type of system can be used to investigate how T cells become suppressed during tumorigenesis, and how immunotherapies counteract immunosuppression. This minireview will provide a brief overview of the use of human umbilical cord blood transplanted into immunodeficient murine hosts to model antitumor responses.
Topics: Animals; Blood Transfusion; Disease Models, Animal; Fetal Blood; Graft Survival; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Immunotherapy; Lymphocyte Activation; Mice; Neoplasms; T-Lymphocytes; Thymus Gland; Xenograft Model Antitumor Assays
PubMed: 29434589
DOI: 10.3389/fimmu.2018.00054 -
Medicine Nov 2022Lipofibroadenoma is an extremely rare thymic tumor, and the anterior mediastinum is the most common site.
BACKGROUND
Lipofibroadenoma is an extremely rare thymic tumor, and the anterior mediastinum is the most common site.
CASE SUMMARY
A 21-year-old male was admitted with fever without obvious cause for 2 months. After admission, the patient's highest temperature was 38.3°C, accompanied by diarrhea. Physical examination showed coarse breath sounds in both lungs. Chest enhanced computed tomography (CT) showed a mass of mixed density shadow on the left side of the anterior mediastinum with a size of approximately 9.2 cm × 5 cm × 2.1 cm and a clear boundary mixed with a low fat density shadow. Mediastinal tumors were removed under general anesthesia by video-assisted thoracoscopic surgery. Macroscopically, a clear boundary was shown between the tumor and the remaining thymus. Microscopically, the tumor contained a large amount of mature adipose and fibrous tissue with scattered cord-like epithelial tissue and a small number of lymphocytes scattered in the stroma. The tumor lacked thymic bodies. The neoplastic epithelial cells were oval or polygonal and arranged in fissures, the nuclei were uniform in size and mild in shape, and mitosis was rare. Epithelial cells were positive for AE1/AE3 and CK19, lymphocytes were positive for CD3 and CD20, and fat and fibrous tissue were positive for S-100 and vimentin, respectively. The Ki67 labeling index was less than 5%. Based on histological features and immunophenotype, thymic lipofibroadenoma was diagnosed. The patient was followed up 1 year after the operation, and no recurrence or residual lesions were found on the X-ray re-examination.
CONCLUSION
Lipofibroadenoma is a benign thymic tumor, and thymectomy is regarded as the best treatment. The biological behavior of thymic lipofibroadenoma is good, and the recurrence rate is low.
Topics: Humans; Male; Young Adult; Adult; Mediastinum; Thymoma; Thymus Neoplasms; Thymectomy; Mediastinal Neoplasms
PubMed: 36401401
DOI: 10.1097/MD.0000000000031732