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Metabolic Engineering Mar 2022Heparin is an essential anticoagulant used for treating and preventing thrombosis. However, the complexity of heparin has hindered the development of a recombinant...
Heparin is an essential anticoagulant used for treating and preventing thrombosis. However, the complexity of heparin has hindered the development of a recombinant source, making its supply dependent on a vulnerable animal population. In nature, heparin is produced exclusively in mast cells, which are not suitable for commercial production, but mastocytoma cells are readily grown in culture and make heparan sulfate, a closely related glycosaminoglycan that lacks anticoagulant activity. Using gene expression profiling of mast cells as a guide, a multiplex genome engineering strategy was devised to produce heparan sulfate with high anticoagulant potency and to eliminate contaminating chondroitin sulfate from mastocytoma cells. The heparan sulfate purified from engineered cells grown in chemically defined medium has anticoagulant potency that exceeds porcine-derived heparin and confers anticoagulant activity to the blood of healthy mice. This work demonstrates the feasibility of producing recombinant heparin from mammalian cell culture as an alternative to animal sources.
Topics: Animals; Anticoagulants; Gene Editing; Heparin; Heparitin Sulfate; Mice; Swine
PubMed: 35038554
DOI: 10.1016/j.ymben.2022.01.002 -
Indian Dermatology Online Journal 2018
PubMed: 29854655
DOI: 10.4103/idoj.IDOJ_193_17 -
European Annals of Allergy and Clinical... Mar 2020Tryptase is a serin-protease produced and released by mast cells after IgE-mediated or non-IgE mediated stimuli. We here review the various aspects related to the... (Review)
Review
Tryptase is a serin-protease produced and released by mast cells after IgE-mediated or non-IgE mediated stimuli. We here review the various aspects related to the molecular characteristics of the enzyme and its biological effects, the genetic basis of its production and the release kinetics. Recommendations for the clinical use of tryptase measurement developed by a task force of Società Italiana di Patologia Clinica e Medicina di Laboratorio and Associazione Allergologi Immunologi Italiani Territoriali e Ospedalieri are given on the best procedure for a correct definition of the reference values in relation to the inter-individual variability and to the correct determination of tryptase in blood and other biological liquids, in the diagnosis of anaphylaxis (from drugs, food, insect sting, or idiophatic), death from anaphylaxis (post mortem assessment) and cutaneous or clonal mastcell disorders.
Topics: Animals; Humans; Advisory Committees; Allergy and Immunology; Anaphylaxis; Autopsy; Biomarkers; Immunoglobulin E; Italy; Leukemia, Biphenotypic, Acute; Mastocytoma; Mastocytosis; Practice Guidelines as Topic; Reproducibility of Results; Tryptases
PubMed: 31994369
DOI: 10.23822/EurAnnACI.1764-1489.133 -
Actas Dermo-sifiliograficas 2016Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in various organs. The organ most often... (Review)
Review
Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in various organs. The organ most often affected is the skin. Mastocytosis is a relatively rare disorder that affects both sexes equally. It can occur at any age, although it tends to appear in the first decade of life, or later, between the second and fifth decades. Our understanding of the pathophysiology of mastocytosis has improved greatly in recent years, with the discovery that somatic c-kit mutations and aberrant immunophenotypic features have an important role. The clinical manifestations of mastocytosis are diverse, and skin lesions are the key to diagnosis in most patients.
Topics: Female; Humans; Male; Mast Cells; Mastocytosis; Proto-Oncogene Proteins c-kit; Skin
PubMed: 26546030
DOI: 10.1016/j.ad.2015.09.007 -
Dermatology Practical & Conceptual Jul 2022
PubMed: 36159113
DOI: 10.5826/dpc.1203a83 -
The Israel Medical Association Journal... May 2005Mastocytosis is a heterogeneous group of diseases characterized by the abnormal infiltration of mast cells in the skin and, sometimes, other organs. Some patients may... (Review)
Review
BACKGROUND
Mastocytosis is a heterogeneous group of diseases characterized by the abnormal infiltration of mast cells in the skin and, sometimes, other organs. Some patients may experience symptoms related to mast cell mediator release.
OBJECTIVE
To analyze the clinical features of cutaneous mastocytosis in a large series of children.
METHODS
We conducted a file review of all children clinically diagnosed with cutaneous mastocytosis in our department over the last 20 years. We evaluated gender, age at onset, character and distribution of the lesions, associated symptoms, and course of the disease.
RESULTS
Altogether, 180 patients with cutaneous mastocytosis were identified. The male to female ratio was 1.5:1. About one-third of patients had a mastocytoma, which was present at birth in over 40% and appeared during the first year of life in most of the remainder. Urticaria pigmentosa was noted in 65% of the patients, presenting at birth in 20% and during the first year in most of the remainder. The majority of lesions was distributed over the trunk and limbs. Different kinds of associated symptoms were noted. Prognosis in general was good. Only 11% of the cases, all urticaria pigmentosa, were familial.
CONCLUSIONS
Most cases of pediatric mastocytosis are sporadic and appear during the first 2 years of life, especially on the trunk. Urticaria pigmentosa is the most frequent variant. The prognosis of pediatric mastocytosis, in general, is good.
Topics: Adolescent; Age of Onset; Child; Child, Preschool; Comorbidity; Disease Progression; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Israel; Male; Mastocytoma; Mastocytosis, Cutaneous; Prognosis; Urticaria Pigmentosa
PubMed: 15909466
DOI: No ID Found -
Indian Pediatrics Apr 2005
Topics: Female; Humans; Infant; Leg; Mastocytoma
PubMed: 15876605
DOI: No ID Found -
Veterinary Pathology Mar 2022Mast cell tumors (MCTs) are one of the most common cutaneous malignancies in dogs. Previous studies have reported expression of mast cell-specific proteases chymase and...
Mast cell tumors (MCTs) are one of the most common cutaneous malignancies in dogs. Previous studies have reported expression of mast cell-specific proteases chymase and tryptase in canine cutaneous MCTs and in connective tissue and mucosal mast cells. In humans and rodents, mast cells express an additional specific protease, carboxypeptidase A3 (CPA3). In this article, we describe CPA3 immunoreactivity in connective tissue, visceral, mucosal, and neoplastic mast cells in dogs. Positive immunolabeling for CPA3 was observed in nonneoplastic mast cells in 20/20 formalin-fixed paraffin-embedded normal tissues (skin, liver, spleen, intestine), and in 63/63 MCTs irrespective of their histological grade. CPA3 protein expression was comparable to that of c-kit in both the nonneoplastic and neoplastic mast cells. Three distinct labeling patterns (membranous, diffuse, and focal cytoplasmic) were observed for CPA3 in MCTs. The focal cytoplasmic labeling pattern was associated with high-grade MCTs staged with the Kiupel 2-tier grading criteria. We propose CPA3 as a novel immunohistochemical marker for canine mast cells in health and disease.
Topics: Animals; Carboxypeptidases; Dog Diseases; Dogs; Mast Cells; Proto-Oncogene Proteins c-kit; Skin Neoplasms; Tryptases
PubMed: 34894899
DOI: 10.1177/03009858211062636 -
Journal of Veterinary Diagnostic... Mar 2022Quantitative morphologic parameters assessed in cytologic samples of canine cutaneous mast cell tumors (ccMCTs) may assist with surgical planning and prognostication....
Quantitative morphologic parameters assessed in cytologic samples of canine cutaneous mast cell tumors (ccMCTs) may assist with surgical planning and prognostication. Robust cutoffs can be defined, with high reproducibility, for parameters such as the nuclear area (NA). The NA may be determined by morphometry (image analysis, NAI) or by stereology, such as the 2D-nucleator method (NAN); stereologic techniques have not been applied to cytologic specimens of ccMCT, to our knowledge. We retrospectively selected routine cytology smears from 51 ccMCT cases and screened them to determine the percentage of neoplastic mast cells with indistinct nuclear borders; this was repeated after the slides were restained with H&E. The NAI and the NAN were estimated in 100 mast cells per animal in H&E-stained slides. All nuclei were visible in H&E smears, and unbiased quantification was feasible. The NAN was similar to NAI, but less time-consuming. Both the NAN and NAI determined by cytology differed in histologic low- and high-grade ccMCTs, and in histologic grade I plus II versus grade III ccMCTs. Stereologic parameters such as the NAN could be considered as complementary techniques for the cytologic evaluation of ccMCTs.
Topics: Animals; Cytodiagnosis; Dog Diseases; Dogs; Mastocytoma, Skin; Reproducibility of Results; Retrospective Studies
PubMed: 34763591
DOI: 10.1177/10406387211058825 -
Animals : An Open Access Journal From... Apr 2020Spaying and neutering dogs is commonly used to prevent the birth of unwanted animals and eliminate the risk of reproductive diseases. However, removal of the gonads... (Review)
Review
Spaying and neutering dogs is commonly used to prevent the birth of unwanted animals and eliminate the risk of reproductive diseases. However, removal of the gonads prevents the feedback of estrogen and testosterone on the pituitary and hypothalamus. As a result, luteinizing hormone (LH) is continuously elevated at supraphysiologic concentrations. Although the main role of LH is for reproductive function (e.g., ovulation), there are LH receptors present in several normal tissues including the thyroid and adrenal glands, gastrointestinal tract, cranial cruciate ligament and round ligament, and lymphocytes. In addition, there are LH receptors present in several neoplastic tissues (e.g., lymphoma, hemangiosarcoma, mastocytoma, transitional cell carcinoma, and osteosarcoma). The role of LH receptors in non-reproductive normal and neoplastic tissues is not known but may stimulate nitric oxide release and induce cell division. The precise etiology of the increased incidence of several non-reproductive long-term health complications following spaying and neutering is not known but may be related to LH receptor activation in these non-reproductive target tissues. How these effects may be mediated is described in this review.
PubMed: 32244716
DOI: 10.3390/ani10040599