Search PubMed⌕ Search

Biomedical subjects

D D Metcalfe

Publications and source records attributed to D D Metcalfe.

248 records · Page 14Linked to original sources
PubMed1979

Human platelet arylsulphatases: identification and capacity to destroy SRS-A.

Arylsulphatases IIA and IIB have been separately identified in human platelets by use of anion exchange chromatography and gel filtration. Arylsulphatase IIA had a molecular weight of 160,000 and a pH optimum of 4.5. Arylsulphatase IIB had a molecular weight of 60,000 and a pH optimum of 5.5. Both arylsulphatases IIA and IIB were inhibited by phosphate and sulphate ions characteristic of this enzyme class. Platelets, upon exposure to ionophore A-23187 or thrombin, discharged arylsulphatase coincident with beta-glcuronidase release. Partially purified platelet arylsulphatase IIB inactivated rat SRS-A.

Arylsulfatases↗
PubMedDate not supplied

Further characterization of FcgammaRII and FcgammaRIII expression by cultured human mast cells.

BACKGROUND: We have reported that resting human mast cells exhibit minimal expression for FcgammaRI, and that interferon-gamma will upregulate this expression. The expression of FcgammaRII and FcgammaRIII by human mast cells remains to be fully examined. METHODS: To investigate FcgammaRII and FcgammaRIII expression, we determined mRNA and protein expression of FcgammaRII and FcgammaRIII in human peripheral blood CD34+ derived cultured mast cells by RT-PCR and flow cytometry. The expression of FcgammaRII and FcgammaRIII in intact and permeabilized mast cells was also compared. We measured histamine release to monitor mast cell degranulation following cross-linking of FcgammaRII. RESULTS: We found by RT-PCR that resting human mast cells exhibit mRNA for FcgammaRIIA, FcgammaRIIb1, FcgammaRIIb2 and FcgammaRIII but not FcgammaRIIC. FACS analysis of Fcgamma receptors in intact versus permeabilized mast cells showed expression of FcgammaRII to be 42.2 +/- 3.9% and this was unchanged by permeabilization. FcgammaRIII protein expression was minimal and this was also unchanged by permeabilization. Aggregation of FcgammaRII on human mast cells led to no significant degranulation as evidenced by histamine release. CONCLUSIONS: In addition to FcgammaRI expression, human mast cells express FcgammaRIIA, FcgammaRIIb1, FcgammaRIIb2 and FcgammaRIII mRNA, and significant surface expression of FcgammaRII. Aggregation of FcgammaRII on cultured human mast cells in this model was not followed by histamine release.

Cells, Cultured↗
PubMedDate not supplied

Interaction of mast cells with extracellular matrix proteins.

It is possible to divide surface receptors on mast cells conceptually into three groups. The first consists of immune response receptors. The index receptor for this group is Fc epsilon RI, now joined by Fc gamma receptors and receptors for complement products. The second group of receptors are those that are involved in growth and differentiation, such as those for interleukin-3 and stem cell factor. The third group consists of receptors regulating mast cell trafficking and distribution. Principle among the latter group of receptors are those that engage extracellular matrix components, including the classical integrin receptors. The engagement of mast cells to matrix components not only has relevance in determining the tissue distribution of mast cells, but also appears to have a major influence on the biologic responsiveness of mast cells to immune- and growth-factor-receptor-mediated signals.

Amino Acid Sequence↗
PubMedDate not supplied

The role of c-Kit and its ligand, stem cell factor, in mast cell apoptosis.

The regulation of tissue mast cell number depends both on the rate of production of mast cell precursors and the length of survival of mature mast cells within tissues. Once mast cell precursors target to tissues, their survival may largely be dependent upon the local production of stem cell factor (SCF). Withdrawal of interleukin (IL)-3 results in mast cell apoptosis. The apoptotic changes following IL-3 deprivation are prevented by the addition of SCF which exerts its rescue effect upon interaction with its c-Kit tyrosine kinase receptor. Mast cells undergo apoptosis on withdrawal of IL-3 coincident with a decrease in endogenous bcl-2 mRNA; however, SCF does not induce expression of bcl-2 when added to these cells. When overexpressed, bcl-2 prolongs survival of bcl-2-transfected mast cells following IL-3 deprivation. Transforming growth factor-beta was found to specifically prevent this SCF-mediated rescue from apoptosis, probably by down-regulating the expression of c-Kit. Thus, microenvironmental factors play an important role in regulating mast cell numbers by effecting survival in the periphery.

Animals↗
PubMedDate not supplied

c-kit mutation in a population of patients with mastocytosis.

The c-kit Asp816Val activating mutation is found in all patients with mastocytosis with an associated hematologic disorder, and at least in a subset of patients with indolent mastocytosis. The case of an 11-month-old child is presented who was categorized as having indolent mastocytosis, and where the Asp816Val mutation was identified in lesional skin, but not in bone marrow or in peripheral blood mononuclear cell populations. The significance of these findings is discussed.

Humans↗
PubMedDate not supplied

Differential diagnosis of the patient with unexplained flushing/anaphylaxis.

In unusual cases of flushing and anaphylaxis, and after the elimination of the more obvious causes of anaphylaxis or those that may be evaluated by readily available techniques, it is possible to confront a limited and difficult differential diagnosis, which includes idiopathic flushing, anaphylaxis, and neoplastic syndromes associated with mastocytosis and carcinoid tumor. Interestingly, there are rather few features that distinguish one of these possibilities from another. However, the presence of allergic signs and symptoms tend to favor the diagnosis of recurrent idiopathic anaphylaxis; and right-sided valvular heart disease, the presence of excessive 5-HIAA in the urine, and a response to somatostatin favor the diagnosis of carcinoid syndrome. The distinguishing features of mastocytosis include the presence of characteristic skin lesions and diagnostic histopathologic findings on bone marrow biopsy. Counts of absolute mast cell numbers in the skin are less helpful. Following such guidelines, it is often possible to focus on the most likely diagnosis, be it idiopathic anaphylaxis, benign cutaneous flushing, mastocytosis, or carcinoid tumor.

Algorithms↗
PubMedDate not supplied

Mast cells in allergy and host defense.

Mast cells have been implicated in the pathogenesis of allergic diseases and in inflammatory responses associated with pathological immune and disease-related processes including fibrosis, autoimmune pathology, and neoplasia. Recent findings in animal models of bacterial infection also suggest that mast cells may have a protective role in host defense against pathogens in innate immunity along with the probable role of mast cells in acquired immunity against parasitic infections. Mast cells are strategically located at the host-environment interface and may provide an early defense against an invading pathogen. Mast cells express an array of adhesion and immune receptors that may assist in the recognition of invading pathogens. When activated, these cells then synthesize and release key immunoregulatory cytokines, one consequence of which is to mobilize a rapid and vigorous inflammatory response. However, although it has been demonstrated that mast cells may have a role in innate immunity in defined in vitro and animal models, it remains to be determined whether mast cells are protective in innate immune responses in humans.

Antigen Presentation↗
PubMedDate not supplied

Histamine in foods: its possible role in non-allergic adverse reactions to ingestants.

Histamine is well recognized as a product of both mast cells and basophils. Its release from these sources in IgE-mediated reactions unquestionably contributes to the allergic response. It is often stated that ingestion of foods rich in histamine can result in absorption of sufficient histamine to provoke signs and symptoms reminiscent of an allergic reaction. A review of literature relevant to this issue suggests that certain foods do indeed contain histamine as measured by current methodology. Further, histamine ingestion in excess of 36 to 250 mg may or may not result in a clinical response which includes abdominal complaints, feelings of warmth, flushing and headache. Taken together, this evidence supports the hypothesis that ingestion of large amounts of histamine-containing foods or foods which contain the histamine precursor, histidine, under some circumstances can result in adverse reactions.

Animals↗
PubMedDate not supplied

A current practical approach to the diagnosis of suspected adverse reactions to foods.

The diagnosis of adverse reactions to foods and food additives continues to rely on the history and physical examination supported by the judicious use of specific procedures. These include, where applicable, elimination diets, skin testing using water soluble food extracts, in vitro tests for the measurement of food-specific IgE, and, in selected cases, oral challenge with suspect food antigens and additives. The advantages and the disadvantages of the various procedures are examined.

Allergens↗
PubMedDate not supplied

Mastocytosis in infants and children: recognition of patterns of skin disease.

Mastocytosis is a disease characterized by an increase in the number of tissue mast cells and a concomitant increase in mast cell-derived mediators. To demonstrate the spectrum of skin disease in mastocytosis in the pediatric population, five children with mastocytosis and complaints of urticaria (4/5), bullae/vesicles (3/5), abdominal pain (3/5), flushing (2/5), headache (1/5), and bone pain (1/5) are reviewed. Confirmation of the diagnosis of cutaneous mastocytosis was obtained by histologic examination of a biopsy of lesional skin; however, mast cell numbers in lesional skin did not correlate with plasma histamine levels or the extent of cutaneous involvement. Mastocytosis is a diagnosis that must be recognized in the differential diagnosis of pediatric urticarial diseases.

Adult↗
PubMedDate not supplied

Contemporary issues in mast cell biology.

Mast cells are the principal initial effector cells in the modulation of allergic inflammation. They are now known to arise from CD34+ pluripotential stem cells, circulate through the blood as CD34+, Fc epsilon RI-, Kit+ committed but undifferentiated cells, and migrate into tissues where they mature in the presence of Kit-ligand (stem cell factor) and other locally produced cytokines. Mast cells undergo programmed cell death (apoptosis) when stem cell factor is not available. Mast cells adhere to specific connective tissue components such as fibronectin and laminin. This interaction localizes mast cells to specific sites while altering their biologic responsiveness. Mast cells, when activated through Fc epsilon RI, release and generate a wide variety of cytokines including IL-4 and IL-5. This information provides new insights on how allergic reactions may be modified by developing strategies to effect mast cell viability, survival and localization; and the production of inflammatory mediators.

Animals↗