Meir Shalit

PROLONGED ATYPICAL ILLNESS ASSOCIATED WITH SEROLOGICAL EVIDENCE OF PERSISTENT EPSTEIN-BARR VIRUS INFECTION

Seven patients with prolonged atypical illness were followed up for more than a year. Sera taken during that period showed significantly increased titres of IgM antibodies against the viral capsid antigen (VCA) of Epstein-Barr virus (EBV). In four of the patients antibodies to the R component of the early antigen (EA) complex of EBV were clearly detectable. Only one of these seven patients had presented with symptoms of classic infectious mononucleosis. Serological and clinical observations in these patients suggest that the prolonged atypical illness was probably the result of persistent EBV infection.

Mast cells in experimental allergic encephalomyelitis: characterization, distribution in the CNS and in vitro activation by myelin basic protein and neuropeptides.

Mast cells (MC) have been implicated in the pathogenesis of experimental allergic encephalomyelitis (EAE). In order to further evaluate their role, several morphological and functional studies were performed. Semiquantitative counts of histological sections showed a significant reduction in MC numbers in EAE brains. In addition, a higher proportion of EAE MC (about 50-70%) appeared degranulated compared with about 20% degranulation in controls. Central nervous system (CNS) MC exhibited staining properties of connective tissue MC and about 98% of them, both in diseased and control rats, were located in the thalamus. They were not present in the spinal cord and did not relate to EAE lesions. In vitro incubation of peritoneal MC (of connective tissue phenotype) with either MBP, or with neuropeptides such as substance P or bradykinin resulted in release of beta-hexosaminidase and histamine. The latter responses were similar in both EAE and control rats. It is suggested that the decrease in number and in granular content of CNS MC in EAE may reflect prior in vivo activation. The fact that MC were activated by MBP and by neuropeptides in vitro suggests a possible mechanism of MC activation in EAE.

Differential Release of Histamine and Prostaglandin D2 in Rat Peritoneal Mast Cells Activated with Peptides

Rat peritoneal mast cells co-cultured with mouse 3T3 fibroblasts (MC/3T3) are fully responsive to immunologic stimuli. To assess their nonimmunologic activation MC/3T3 were challenged with various peptides. Optimal concentrations of substance P (10(-4) M) and bradykinin (5 x 10(-5) M) induced histamine release of 58.2 +/- 9.3 and 66.8 +/- 6.6%, respectively, while neurotensin (10(-4) M) released only 16.6 +/- 3.7% histamine. Freshly isolated mast cells (F-MC) challenged with the same concentrations of peptides released lower percentages of histamine (substance P 45.6 +/- 5.1%, bradykinin 32.5 +/- 5.3%, neurotensin 11.3 +/- 6.0%). In both MC/3T3 and F-MC, only minute amounts of prostaglandin D2 (PGD2) were produced. In contrast, activation with anti-IgE antibodies and compound 48/80 caused both histamine release and PGD2 generation. Compound 48/80-stimulated MC/3T3 and F-MC released 80.2 +/- 3.4 and 51.8 +/- 6.2% histamine, respectively, and produced 15.4 +/- 2.8 ng/10(6) mast cells and 3.9 +/- 1.4 ng/10(6) mast cells PGD2, respectively. These findings indicate that peptides and bradykinin induce selective release of histamine with no PGD2 production in both F-MC and MC/3T3. Moreover, MC/3T3 preserve their functional characteristics of connective tissue mast cells since they are fully responsive to these peptides as F-MC.

The Hypereosinophilic Syndrome Associated with CD4+CD3″ Helper Type 2 (Th2) Lymphocytes

We describe herein the clinical and laboratory manifestations of a unique group of patients (pts) presenting with hypereosinophilic syndrome (HES) who were treated in our medical centers for 4–13 years. Skin biopsies, flow cytometry of peripheral blood mononuclear cells (PBMC), assays for cytokines and immunoglobulin (Ig) production in vitro, and Southern blots of T-cell receptor (TCR) genes were performed. All four pts had a persistent hypereosinophilia (>1.9 × 109/L) and chronic skin rash. Three of four had elevated IgE, thrombotic manifestations and lung involvement (asthma and/or infiltrates), and one had deforming sero-negative arthritis of the hands. 66–95% of their peripheral T-cells expressed CD4 but not CD3 or TCR molecules on the cell surface membrane. Activated CD4+CD3- cells secreted interleukin (IL)- 4 and/or 5, and were required for maximal IgE secretion by autologous B-cells. Two pts had evidence of rearrangement of TCR genes of the CD4+CD3- cells, one of whom died of anaplastic lymphoma. In conclusion, HES with CD4+CD3- lymphocytosis may be associated with high serum IgE, dermatological, pulmonary, thrombotic and rheumatic manifestations which may be due to Th2 effects of CD4+CD3-cells migrating to end organs. Fatal systemic lymphoid malignancy may also develop in some pts with monoclonal expansion of the CD4+CD3- T-cells.

Challenge of mast cells with increasing amounts of antigen induces desensitization

Background In vivo rush desensitization is a procedure widely employed to quickly desensitizo allergic patients by administering increasing doses of the offending antigen at short intervals. The mechanism(s) underlying this process and the possible role of mast cells in it have not been well delineated.

Acute Nonrheumatic Perimyocarditis Complicating Streptococcal Tonsillitis

Streptococcal infection is a rarely recognized cause of nonrheumatic perimyocarditis. We report a case of a young patient who developed acute perimyocarditis as manifested by diffuse electrocardiogram changes, and markedly elevated cardiac enzymes, concurrently with streptococcal tonsillitis. Despite the dramatic presentation, the patient recovered uneventfully. We conclude that streptococci can involve the heart also directly by a bacterial component or toxin, and not only through a delayed immunologic mechanism as in rheumatic fever. Further studies are necessary to accurately determine the incidence of myocardial involvement during early stages of streptococcal infection.

Metastatic Carcinoma Presenting with Concomitant Eosinophilia and Thromboembolism

A case of a 58-year-old female patient who presented with significant blood eosinophilia and thromboembolic events is described. The patient was eventually diagnosed as suffering from a disseminated malignancy of gastrointestinal origin. Immunohistochemical studies of the tumor are presented. These studies show that tumor cells produce interleukin-3 and -5 and granulocyte macrophage-colony stimulating factor. These cytokines are known to support differentiation, proliferation, and survival of eosinophils. Their secretion is the probable explanation for the appearance of high blood eosinophilia in this patient. To the best of our knowledge, combined blood eosinophilia and thromboembolism as presenting manifestations of a solid tumor have never been reported.

Treating through hypersensitivity to co-trimoxazole in AIDS patients

our series) and the short interval between disease onset and excision, suggesting rapid progression. Women with HIV infection are at high risk of harbouring human papillomavirus (HPV) and of acquiring genital tract infection.5 HPV type 16 has been demonstrated in neoplastic lesions from the conjunctiva and cornea,8 and further studies are needed to determine the interactions between HIV and HPV in the production of neoplastic lesions at different sites. HIV infection seems to be a risk factor for conjunctival neoplasia. The occurrence of such lesions in areas of high HIV seroprevalence justifies antibody testing. Prompt and complete surgical excision should be the rule in HIV seropositive patients because rapid progression is likely in patients with depressed immune responses.

Saliva Secretion in Patients with Allergic Rhinitis

Background: Allergic rhinitis is manifested by watery discharge; however its clinical effect on the watery volume in the oral cavity is unknown. In addition, the low incidence of dry mouth due to treatment with the new generation antihistamines is based on subjective patients’ reports only. This study aimed to examine the effect of loratadine and fexofenadine on the salivary gland function in patients diagnosed with allergic rhinitis compared to untreated allergic patients and healthy individuals. Methods: A comparative observational study assessed parameters related to the patients’ perception of dry mouth as well as clinically observed parameters in fexofenadine-treated patients (group A) and in loratadine-treated patients (group B). Allergic patients without pharmacological treatment (group C) and healthy individuals (group D) served as a double control in order to evaluate the effect of allergy itself on dry mouth. A total of 36 patients were enrolled. Results: Patients in groups A and C reported the highest intensity of xerostomia. Sialometry values were significantly lower in these 2 groups compared to the healthy controls (p = 0.02 and 0.03, respectively). Average sialometry was over 0.2 ml/min in all groups and subjective dry mouth sensation ranged in the lower quarter of the visual analogue scale. Conclusions: In this pilot study, patients diagnosed with allergy presented a significant difference in salivary flow rate compared to healthy controls. Unlike the effect of loratadine, fexofenadine-treated patients showed significantly lower salivary flow rates compared to healthy individuals. In all cases the intensity of dry mouth was low.

Interaction between mast cells and glial cells: an in vitro study

Brain mast cells (MC) are located in close proximity to glial cells and it has been suggested that they belong to the connective tissue phenotype. To determine whether the local microenvironment provided by glial cells can influence mouse bone marrow-derived MC (BMMC), the putative counterpart of mucosal MC, we co-cultured these two cell types. BMMC numbers, morphology, histochemical properties and histamine content as well as glial cell morphology and function were evaluated up to 21 days. Our data indicate that BMMC adhere, proliferate, survive and can be activated to release histamine on the glial cell monolayers without changing their phenotype. Co-cultured glial cells preserve their morphological appearance and function throughout the culture period. These data indicate that central nervous system (CNS) glial cells do not induce phenotypic changes in BMMC and do not interfere with their viability and function.