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PubMed2001

[Clinical variability in two cases of systemic mastocytosis].

Two cases of systemic mastocytosis with different clinical course were described. The first of them manifested with returning attacks of tachycardia with raise of blood pressure, followed by its drop and loss of consciousness. Abdominal pain and persistent diarrhea characterized the second one. The common signs in both cases were skin changes of urticaria pigmentosa, presence of Darier's symptom, very high blood levels of tryptase and prostaglandin D2 and rise in urinary LTE4 concentration. Differential diagnostic is discussed and histopathology bone marrow biopsies are presented.

Adult↗
PubMed2002

Nerve growth factor and eosinophils in inflamed juvenile conjunctival nevus.

PURPOSE: To study both systemic and ocular nerve growth factor (NGF) in inflamed juvenile conjunctival nevus (IJCN), a benign, inflammatory juxtalimbal lesion characterized by many intralesional eosinophils, and to investigate the behavior of eosinophils cocultured on lesional and extralesional fibroblasts obtained from IJCN biopsies, in relation to NGF. METHODS: Eight patients with IJCN (7-15 years old) and six with noninflamed conjunctival compound nevus (12-30 years old) participated in the study. Conjunctival biopsy specimens were used for routine histology, immunohistochemistry (NGF, trkA, eosinophil cationic protein, and tryptase determination), in situ hybridization (NGF mRNA), and determination of fibroblast growth. Blood of patients with IJCN was used to measure NGF levels (by ELISA) and to isolate eosinophils (magnet activated cell sorter [MACS]). Eosinophils were seeded on lesional and extralesional fibroblasts and their adherence, survival (by trypan blue staining), and functional activity (by eosinophil peroxidase [EPO] assay) were assessed after 4 days. RESULTS: NGF in the blood of patients with IJCN and eosinophils and mast cells in their conjunctivas, were significantly elevated. NGF protein, NGF mRNA, and trkA were found to be increased in IJCN biopsy specimens compared with noninflamed compound nevi. Some NGF and trkA colocalized with eosinophils and mast cells. Lesional fibroblasts produced high amounts of NGF in comparison with extralesional fibroblasts and significantly enhanced eosinophil adherence, without influencing either their viability or activation. Adherence and EPO release were increased, in both lesional and extralesional fibroblasts. CONCLUSIONS: The triggering factors that lead to the prominent inflammation in IJCN are unknown. The data in the current study, showing the presence of increased NG-trkA, eosinophils, and mast cells in IJCN and the modulation of eosinophil properties by lesional fibroblasts partly through NGF, suggest a possible association between IJCN and allergic inflammation. Alternatively, this process may represent a direct immune response induced by the nevus itself.

Adolescent↗
PubMed2002

New aspects in thrombosis research: possible role of mast cells as profibrinolytic and antithrombotic cells.

Venous thromboembolism represents a significant cause of morbidity worldwide. The factors that underly thrombophilia are manifold. The concept of Virchow defines the well known triad of stasis, humoral factors, and pathologies of the vascular wall. In the current article, an additional factor, the "accumulation of repair cells" is discussed. This novel concept highlights the mast cell that accumulates around thrombosed vessels and provides a number of important repair molecules including heparin, profibrinolytic tPA, and fibrinogenolytic beta-tryptase. Thus, mast cell recruitment and activation may result in local thrombolysis and prevention of coagulation. In line with this concept, mast cell-deficient mice are more susceptible to lethal thrombogenic stimuli compared to normal mice. The factors (cytokines) that trigger mast cell accumulation and release of repair molecules have also been identified - the most important one appears to be stem cell factor (SCF). All in all. our novel concept suggests that the patho-physiology of thrombosis may involve a "physiologic" cell that provides the same repair molecules that are used for treatment of thrombotic disorders by the physician. Whether an altered availability of components of this cellular repair system can predispose for thrombophilia remains to be determined.

Animals↗
PubMed2002

Preliminary evaluation of mast cells and angiogenesis processes in experimental fibrosarcoma.

The aim of the study was the evaluation of angiogenesis processes in fibrosarcoma induced by 3-methylcholanthrene (3-Mc) in reference to the number of mast cells (MCs). 76 male Wistar rats were divided into 4 groups: two experimental (E) groups--after injection of 0.2 mg 3-Mc dissolved in olive oil (0.25ml), and 2 control (C) groups. In E1 group, 52 rats were killed after development of the fibrosarcoma; E(2)--10 rats were killed before development of the tumor; C(1)-8 rats received 0.25ml olive oil; C(2)--8 rats received no treatment. Tissue material was fixed in buffered formalin or Carnoy's and Bouin's fluid. Paraffin sections were stained with H+E and Azan methods, and with alcian blue-saphranine and toluidine blue. Immunohistochemical reactions detecting tryptase in MCs were also performed. Angiogenic objects (microvessels and single endothelial cells) were recognized using antibodies against factor VIII (vWF), P selectin (CD-62P), and CD-90. We found a distinct relationship between intensification of neoangiogenesis at the tumor periphery and increased number of MCs.

Animals↗
PubMed2003

Proteinase-activated receptor-2 mediates itch: a novel pathway for pruritus in human skin.

We examined whether neuronal proteinase-activated receptor-2 (PAR-2) may be involved in pruritus of human skin. The endogenous PAR-2 agonist tryptase was increased up to fourfold in atopic dermatitis (AD) patients. PAR-2 was markedly enhanced on primary afferent nerve fibers in skin biopsies of AD patients. Intracutaneous injection of endogenous PAR-2 agonists provoked enhanced and prolonged itch when applied intralesionally. Moreover, itch upon mast cell degranulation was abolished by local antihistamines in controls but prevailed in AD patients. Thus, we identified enhanced PAR-2 signaling as a new link between inflammatory and sensory phenomena in AD patients. PAR-2 therefore represents a promising therapeutic target for the treatment of cutaneous neurogenic inflammation and pruritus.

Adult↗
PubMed1992

[Measurement of mediators in drug allergies. Preliminary study].

Drug allergy is still a region where diagnosis remains difficult. It relies on clinical history, sometimes skin tests and lymphoblast transformation tests, though only when the antigen is soluble. Provocation tests may, if there is a doubt, prove the involvement of the drug. It may be made objective by the measurement of mediators: ECD and tryptase, thus showing the involvement of eosinophils and mastocytes. Should change in these mediators be associated with a syndromic reaction or is it on its own, a diagnostic factor? A complementary study with a reference group, on a sufficient number of patients has allowed, with the assistance of a statistical analysis, better objectivity from the results.

Adult↗
PubMed2004

Anaphylaxis to anaesthetic drugs.

Severe anaphylactic reactions during anaesthesia increased dramatically in incidence in the mid 1970s. Studies performed in our unit over the subsequent 25 years demonstrated the involvement of IgE in these reactions and the value and safety of intradermal and prick testing in the diagnosis and determination of the drug responsible. Radioimmunoassay studies demonstrated that neuromuscular blocking drugs produce anaphylaxis by cross-linking IgE molecules via their substituted ammonium groups. The IgE binding of these drugs leads to a high incidence of cross sensitivity. Mast cell tryptase measurement is highly sensitive and specific for anaphylaxis although it can be elevated in reactions due to direct histamine release. The reactions are unpredictable from the history. The heart is rarely a target organ in human anaphylaxis although the diseased heart is more likely to fail or produce serious arrhythmias than the normal heart. Colloid solutions produce a better response than crystalloid solutions in the treatment of hypotension. Anaesthetic allergy persists up to 27 years. Subsequent anaesthesia based on the findings of skin testing is usually safe.

Anaphylaxis↗
PubMed2004

[Relationship between epithelial-immunologic cells transdifferentiation and pseudoepitheliomatous granuloma lesion].

OBJECTIVE: Inappropriate treatment at early stage of wound could result in the formation of pseudoepitheliomatous granuloma (PEG). The correlation of abnormal transdifferentiation of epithelial cells to immunologic cells and the occurrence of PEG lesion was investigated. METHODS: Morphological change of epithelial tissue was observed with histopathology in 11 specimens of PEG lesions and 6 specimens of normal skins from PEG edge (PEG-N) from 11 patients with damaged skin. The expression characteristics and distribution of pan-cytokeratin (CKp), IV type collagen, laminin (LM), epithelial cadherin (E-Cad), beta-catenin (beta-Cat), focal adhesion kinase (FAK), stem cell factor (SCF) and its receptor-c-Kit, proliferating cell nuclear antigen(PCNA), and cluster of differentiation-14 (CD14), CD68 and mast cell tryptase (MCT) in PEG were detected with the immunohistochemical and the indirect immunofluorescent double-staining. RESULTS: In comparison with PEG-N, epithelial tissue take on squamous metaplasia, and stroma was infiltrated with intensive microvessels and inflammatory cells in the PEG lesion. Poor epithelial basal layer constitution, basal polarization, and migration of basal cells to stroma could be observed. In the ultrastructure, the loose intercellular junction of basal cells and the increased nucleus/cytoplasm ratio and intercellular space could be observed, neonatal monocytoid cells and macrophages and mast cells as a exuviate-like manner brooded from cytoplasm of original epithelial cells and basement membrane. protein expression of CKp and E-Cad by basal cells was significantly decreased, and the IV type collagen and LM protein could not be found in basement membrane of identical locus. By contrast, the immunoreactivity of beta-Cat and FAK was apparently increased. In addition, CD14(+) monocytes, CD68(+) macrophages, MCT(+) mast cells and CD68(+)/MCT(+) cells with various size, and these cells of stronger immuno-staining of SCF, c-Kit and PCNA antigen could be found in epithelial tissue and stroma. CONCLUSION: Epithelial cells in PEG related to wound are characteristized by transdifferentiation of epithelial cells to immunologic cells, wich may be associated with local infectious and inflammatory reaction, ultimately resulting in enhancement the ratio of beta-Cat/E-Cad signal and activation SCF-c-Kit signal pathway. The phenomena of transdifferentiation epithelial cells in the PEG lesion will help to recognize of the neoplatic immune and trauma repair mechanism.

Adolescent↗
PubMed2004

[The distribution of mast cells in benign and malignant prostate lesions and its biologic significance].

OBJECTIVE: To study the distribution profile of mast cells in benign and malignant prostate lesions and its biologic significance. METHODS: Fifty-three prostate specimens collected from 2000 through 2002 were examined, and the distribution of mast cells were analyzed. The paraffin sections were stained with anti-human mast cell tryptase immunohistologically. The numbers of cells stained with positive results in ten high-power fields were counted, and the mean was calculated. RESULTS: No significant relationship of mast cell distribution to inflammation in benign prostatic hyperplasias was observed. Significant differences between the mean mast cell numbers of intratumoral region and those of peritumoral region were noted (P<0.05). There was statistically significant difference in the mean mast cell numbers between well-differentiated groups and poorly-differentiated groups (P>0.05). CONCLUSION: There exists a relationship between prostate carcinoma tissue and mast cells. Mast cells may inhabit the tumor cells by different pathways.

Adenocarcinoma↗
PubMed2001

[Clinical and immunohistoenzymatic investigations in patients with vasomotor and perennial allergic rhinitis].

The aim of our study was evaluation of the results of clinical examination in patients with vasomotor and perennial allergic rhinitis and assessment of number of blood vessels, nerve fibres and mast cells on the basis of immunohistoenzymatic examination. There were 42 patients examined aged from 18 to 50 and divided into three groups: I--16 patients with vasomotor rhinitis and II--14 patients with perennial allergic rhinitis and III--12 patients (control) with nasal septum deviation. On the basis of the patient's history data, clinical otorhinolaryngologic examination and active anterior rhinomanometry the patients were qualified to bilateral inferior turbinectomy. The nasal mucosa removed during surgery underwent immunohistoenzymatic examination using the monoclonal antibody against the tryptase of mast cells (MCT company, DAKO), the endothelin of blood vessels (EC - DAKO) and the neurospecific enolase (NSE - DAKO). In examined groups of patients with vasomotor and perennial allergic rhinitis and control group similar escalation of clinical symptoms expressed by means of points index were stated. In immunohistoenzymatic studies the differences in mean number of blood vessels and nerve fibres between examined groups were not statistically significant, however statistically significant difference concerned higher number of mast cells patients with vasomotor rhinitis in comparison to perennial allergic rhinitis.

Adult↗
PubMed2005

Seasonal non-allergic rhinitis (SNAR)--a new disease entity? A clinical and immunological comparison between SNAR, seasonal allergic rhinitis and persistent non-allergic rhinitis.

We have earlier described a group of patients suffering from rhino-conjunctivitis during the early pollen season, but with negative allergological investigation. The present study aimed to evaluate this syndrome called Seasonal Non-Allergic Rhinitis (SNAR). Seventeen patients with SNAR were compared with 20 patients with seasonal allergic rhinitis (SAR) and 13 patients with persistent non-allergic rhinitis (PNAR). They were analyzed with skin prick tests (SPT) and nasal provocation tests (NPT) with pollen extracts, and for IgE antibodies in serum and inflammation mediators in nasal lavage. Daily symptoms and medicine consumption were recorded. Late reactions after SPT occurred in two SNAR, eight SAR and two PNAR patients. Weak immediate and late reactions after NPT were induced in 3/15 and 7/15 SNAR patients, respectively, and in 1/13 and 5/13 PNAR patients. All SAR patients had immediate and 9/18 had late reactions. The total IgE levels were lower in SNAR compared to SAR. In the SNAR group 1/15 was positive in Phadiatop. Increased tryptase levels after NPT were only observed in SAR. The SNAR patients had high daily symptom scores already before birch pollen season. Sneezing was more common in SNAR and SAR than in PNAR; eye-symptoms more prominent in SAR than in SNAR or PNAR. SNAR seems to be different from SAR and PNAR regarding immunological mechanism and symptom period. We conclude that the cause of SNAR is unknown.

Adolescent↗
PubMedDate not supplied

Spatial distribution of mast cells in chronic venous leg ulcers.

Chronic venous leg ulcers (CVUs) show chronic inflammation but different pathological changes occur in different parts of the ulcer. There is a lack of re-epithelialisation and defective matrix deposition in the ulcer base but epidermal hyperproliferation and increased matrix deposition in the surrounding skin. The role of mast cells in wound healing, inflammation, fibrosis and epidermal hyperproliferation has been extensively studied but less is known about their role in CVUs. In the present study, we investigated the distribution of mast cells in CVUs with specific consideration of the differences between the ulcer base and the skin surrounding the ulcer. Both histochemical and immunohistological methods were used to detect the mast cell marker tryptase in frozen sections of CVU biopsies. Mast cells were counted in the dermis of normal skin, in the ulcer base and in the skin surrounding the ulcer. Double immunofluorescence staining was used to study the location of mast cells in relation to blood vessels. In normal skin few mast cells were seen in the dermis but none in the epidermis. However in CVUs there was a significant increase in intact and degranulated mast cells in the surrounding skin and ulcer edge (184 per field, p<0.003) of CVUs and a significant reduction in the ulcer base (20.5 per field p<0.05) in comparison to normal skin (61 per field). In CVUs mast cells showed a characteristic location near the epithelial basement membrane whilst mast cell granules and phantom cells (mast cells devoid of granules) were predominantly seen in the epidermis. In the dermis, mast cells were seen associated with blood vessels. The marked increase in mast cells in the surrounding skin of CVUs and depletion of mast cells in the ulcer base could implicate mast cell mediators in the pathological changes in CVUs particularly in the epidermal and vascular changes occurring in the surrounding skin.

Cell Count↗
PubMed2005

Acute pancreatitis possibly caused by allergy to bananas.

We are reporting a forty-seven year old female who had three attacks of acute pancreatitis after having; eaten bananas. She was treated with a light diet and intravenous fluids during each of her admissions. The treatment concluded with the disappearance of clinical symptoms such as epigastralgia, nausea, vomiting and diarrhea within a few days. In addition, elevated serum and urine amylase levels returned to normal values in parallel with the clinical symptoms. The data during her three attacks of acute pancreatitis were as follows: serum total IgE level = 644 IU/mL, specific IgE to bananas = 2.18 UA/ml. No remarkable abnormalities were present in sonography, computed tomography, magnetic resonance imaging of the abdomen, and magnetic resonance cholangiopancreatography. Endoscopic examination of the upper digestive tract showed the ampulla of Vater swollen and edematous, thus a biopsy was performed. Toluidine blue staining and immunohistochemical staining against human mast cell tryptase with the biopsy specimens showed mast cells accumulating in mucosa and submucosa. By avoiding consumption of bananas, she has not suffered from any additional attacks of pancreatitis since the third attack in the last thirty-four months up to this day of December 10, 2004.

Acute Disease↗
PubMed2005

Intraoperative anaphylaxis: verba volant, scripta manent!

We describe a case of intraoperative gelatine-induced anaphylaxis whose diagnosis was delayed as the use of gelatine during surgical procedures was omitted for two times in patient's medical records. The subject is a 66-year old woman, with a negative medical history of atopy, food and drug allergy, with arterial hypertension on a course of beta-blockers and with bladder carcinoma requiring surgery. The patient had tolerated both general and local anaesthesia on several previous occasions. On the first occasion she experienced arterial fibrillation secondary to a severe episode of hypotension following local anaesthesia, while on a course of beta-blockers. On the second occasion she developed a very severe episode of hypotension followed by the outbreak of a generalised rash during general anaesthesia. The tryptase sera level was 109 mg/L one hour after the reaction had subsided, while the basal values were normal. On the third occasion the patient redeveloped severe hypotension and a generalised rash during general anaesthesia. The allergological work-up was negative, except for intradermal test with gelatine. A study of the intra-cellular cytokines in blood lymphocytes showed a production of IL4 from CD4+ lymphocytes after stimulation by gelatine. The patient underwent a successive surgical procedure without any adverse event.

Adrenergic beta-Antagonists↗
PubMed2006

Patients with psoriatic arthritis have an increased number of lymphocytes in the duodenal mucosa in comparison with patients with psoriasis vulgaris.

OBJECTIVE: To determine if there is evidence of inflammation in the duodenal mucosa in patients with psoriatic arthritis (PsA) and to compare the results with those in patients with psoriasis vulgaris (PsV). METHODS: Nineteen consecutive patients with PsA underwent gastroduodenoscopy, and biopsy specimens were taken from the duodenal and gastric mucosa. In addition to routine processing, the duodenal mucosal specimens were stained for CD3+, CD8+ and CD4+ T lymphocytes, tryptase-positive mast cells, and EG2-positive eosinophil granulocytes. The results were compared with those in duodenal mucosal specimens from patients with PsV and patients with irritable bowel syndrome. RESULTS: Compared with PsV patients (without antibodies against gliadin), patients with PsA had a highly significant increase in intraepithelial CD3+ and CD8+ lymphocytes and also in CD4+ lymphocytes in the lamina propria in the villi. The lymphocyte increase was not related to presence of IgA antibodies against gliadin, endomysium, or transglutaminase, or to concomitant gastritis. Patients with PsA and PsV showed a pronounced increase in mast cells and eosinophil granulocytes. CONCLUSION: The increased lymphocyte infiltration in the duodenal mucosa in PsA, but not in PsV, might indicate different pathogenetic mechanisms in these psoriasis variants.

Adult↗
PubMed2006

[Role of mast cells and eosinophil cationic protein in the pathogenesis of Henoch-Schonlein purpura nephritis].

OBJECTIVE: Mast cells and eosinophil have been found to play important roles not only in the development of anaphylactic inflammation but also in the chronic progression of organ reconstruction. But their role in the pathogenesis of Henoch-Schonlein purpura nephritis (HSPN) has not been fully understood. The present study was conducted to observe the serum levels of eosinophil cationic protein (ECP) and renal infiltration of mast cells in HSPN in order to elucidate their role in the development and progression of HSPN in children. METHODS: The serum ECP levels were determined in 46 children with HSPN by fluoro-enzyme immunoassay (FEIA) using the Pharmacia CAP System. The distribution of mast cells infiltration was detected by immuno-enzyme-histological staining of tryptase (a marker for mast cell activation) and their relation with pathological changes was analyzed in 32 children with HSPN. RESULTS: The serum ECP levels were 16.3 +/- 6.5 microg/L in the active stage of HSPN, significantly higher than that in remission stage (3.9 +/- 1.4 microg/L, P < 0.01) and that in control group (3.1 +/- 1.7 microg/L, P < 0.01). The number of mast cells in renal interstitium was 4.4 +/- 2.4 cells/mm2 in normal kidney, and significantly increased to 27.2 +/- 19.2 cells/mm2 in children with HSPN ISKDC grade II (P < 0.01) and 42.1 +/- 16.4 cells/mm2 in grade III (P < 0.05 when compared with grade II), 77.9 +/- 15.0 cells/mm2 in grade IV (P < 0.05 when compared with grade III). CONCLUSION: The serum ECP level could reflect disease activity of HSPN, and mast cell infiltration in kidney correlated significantly with renal histological severity in HSPN. Mast cells and eosinophil may play important roles in the development and progression of HSPN.

Biomarkers↗
PubMed2006

[Hydrodistention of the bladder in patients with interstitial cystitis--clinical efficacy and its association with immunohistochemical findings for bladder tissues].

We retrospectively analyzed the clinical relevance of hydrodistention under anesthesia for patients having urgency and/or lower abdominal pain who were clinically diagnosed as having interstitial cystitis (IC) from May 1996 to May 2005. Their symptoms were refractory to anticholinergic or antiinflammatory agents. Hydrodistention was performed under general or spinal anesthesia with direct vision by cystoscopy and irrigation fluid was instilled into the bladder at a pressure of 80 cmH2O. Cystoscopic findings revealed glomerulation in 26 patients (96%), cracking in 10 (37%) and Hunner's ulcer in 3. Twenty-four patients (89%) obtained improvement of the objective symptoms after treatment. However, symptoms soon deteriorated in 16 patients, and the average duration of efficacy was only 4.7 months (SD; +/-3.7). There were two episodes of complication in this treatment. Bladder rupture occurred during hydrodistention, but was successfully managed with simple percutaneous perivesical drainage. One patient with acute pyelonephritis was treated with an antimicrobial agent without any additional treatment. Although bladder specimens were examined by immunohistochemistry, tryptase and c-kit were not linked with the mast cell count, severity of symptoms or treatment efficacy. Hydrodistention of the bladder may be recommended as the first treatment choice for patients with IC because it provides relatively high efficacy. However, the short duration of the efficacy requires a second-line treatment option for better management of patients with IC.

Adult↗
PubMed1991

Cloning of the cDNA and gene of mouse mast cell protease-6. Transcription by progenitor mast cells and mast cells of the connective tissue subclass.

The cDNA and gene for mouse mast cell protease-6 (MMCP-6) have been sequenced and show MMCP-6 to be translated as a prepro-enzyme with a 21-amino acid hydrophobic leader peptide, a 10-amino acid activation peptide, and a 245-amino acid mature enzyme. The mature form of the enzyme has 73% amino acid sequence identity with human and dog mast cell tryptases. The MMCP-6 gene includes 6 exons, with a total span of 1.8 kilobases. A 208-base pair intron was defined which separates the 5'-untranslated sequence of MMCP-6 from the translation initiation codon, thereby presenting a gene organization which distinguishes tryptic serine proteases from chymotryptic serine proteases of the mast cell secretory granule. By RNA blot analysis with a gene-specific probe, MMCP-6 has a unique subclass distribution in being transcribed in mouse connective tissue mast cells but undetectable in mucosal mast cells. MMCP-6 is the first serine protease of any class to be shown to be significantly transcribed in progenitor, bone marrow-derived mast cells, which can reconstitute both mucosal mast cell and connective tissue mast cell populations in mast cell-deficient mice.

Amino Acid Sequence↗