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Biomedical subjects

C Ortolani

Publications and source records attributed to C Ortolani.

At least 55 records · Page 3Linked to original sources

Lack of selective V beta deletion in CD4+ or CD8+ T lymphocytes and functional integrity of T-cell repertoire during acute HIV syndrome.

OBJECTIVE: To study the V beta T-cell repertoire in peripheral blood lymphocytes (PBL) during acute HIV syndrome by using several anti-V beta monoclonal antibodies (MAb) and to analyse its functionality by stimulating PBL with superantigens (SAg) such as Staphylococcus aureus enterotoxins. METHODS: Cytofluorimetric analysis of V beta T-cell-receptor expression was performed on PBL from eight patients with symptomatic, acute HIV-1 primary infection, showing a dramatic decrease of CD4+ PBL accompanied by a marked increase in activated/memory CD8+ T cells, and on 12 age- and sex-matched healthy controls. PBL were then isolated, stimulated with different SAg, anti-CD3 MAb or phytohaemagglutinin and cultured for 3 days. PBL capability to progress through cell cycle was studied by the classic cytofluorimetric method of bromodeoxyuridine incorporation and DNA staining with propidium iodide. RESULTS: Despite the presence of a few expansions of some V beta families among CD8+ T lymphocytes, no gross alterations in T-cell repertoire were present in patients with acute HIV syndrome. Its functionality was maintained overall, as PBL responsiveness to SAg was well preserved. Interestingly, all CD8+ T cells, although bearing different V beta T-cell receptors, expressed marked signs of activation, i.e., CD45R0, CD38 and major histocompatibility complex class II molecules, and also high amounts of CD11a and CD18. CONCLUSIONS: Our data suggest, at least in the early phases and in the acute form of the infection, that HIV is not likely to act as a SAg. However, further studies are needed to analyse other sites, such as lymph nodes, where HIV could exert other, significant effects, and to study the expression of other V beta families than those investigated here.

Acquired Immunodeficiency Syndrome↗

Mechanisms in adverse reactions to food. The mouth and pharynx.

Symptoms appear immediately at the site of contact with the food when a susceptible allergic patients eats the offending food. Allergy to fresh fruits and vegetables, associated with all kinds of pollinosis, is the more frequent cause of Oral Allergy Syndrome.

Allergens↗

Allergenic cross-reactivity among peach, apricot, plum, and cherry in patients with oral allergy syndrome: an in vivo and in vitro study.

BACKGROUND: Oral allergy syndrome in response to fruits and vegetables frequently occurs as clusters of hypersensitivity to members of the same botanical family, for which the immunologic basis lies in a number of common allergens, most of them still unidentified. OBJECTIVE: This study was designed to assess the in vivo and in vitro cross-reactivity between fruits of the Prunoideae subfamily (i.e., peach, cherry, apricot, and plum) and to identify their major allergens and the cross-reactivity of the peach extract with grass and birch pollen. METHODS: The in vivo study was conducted by skin prick tests and open food challenges with fresh fruits in 23 patients with oral allergy syndrome for peach and positive skin prick test and RAST results for the other Prunoideae. In vitro sodium dodecylsulfate-polyacrylamide gel electrophoresis was followed by immunoblotting and immunoblotting-inhibition. RESULTS: A 13 kd component was identified as the only major allergen common to all the Prunoideae, the other major allergens were found at 14 kd in peach and at 30 kd in cherry. Immunoblotting inhibition showed wide cross-reactivity within the Prunoideae, whereas grass and birch pollen partially inhibited the peach blotting. CONCLUSIONS: Clinical cross-reactivity to Prunoideae is essentially due to a common 13 kd IgE-binding component, which seems to be the most important major allergen of this subfamily, not shared with grass and birch pollen.

Allergens↗

Effects of nedocromil sodium on bronchospasm and HS-NCA release induced by allergen inhalation in asthmatic patients.

The aim of this study was to assess the ability of nedocromil sodium (NS) to prevent the immediate asthmatic reaction and the increase in the serum level of heat stable neutrophil chemotactic activity (HS-NCA) induced by antigen inhalation. In a double-blind, cross-over study, 13 atopic subjects affected with seasonal asthma underwent a bronchial provocation test with a preselected dose of grass pollen allergen (enough to cause a decrease of > or = 20% in FEV1:FEV1 PD20) after pre-treatment with 4 mg NS or placebo. Serum samples were withdrawn from 11 subjects for HS-NCA determination. After NS administration the decrease in FEV1 was significantly less than after placebo administration at all time points after challenge (2 min P = 0.0004; 7 min, P = 0.0005; 17 min P = 0.0002 and 27 min P = 0.0005). The percentage increase in HS-NCA was significantly higher after placebo than after NS inhalation, both 10 (P = 0.0048) and 20 (P = 0.0068) min after challenge. Our study confirms previous investigations, showing that NS inhibits the immediate asthmatic response to allergen inhalation in atopic, asthmatic subjects and moreover it shows that this drug prevents in vivo the increase of the serum HS-NCA. This last finding has not been previously reported.

Adolescent↗

A double-blind, placebo-controlled study of immunotherapy with an alginate-conjugated extract of Parietaria judaica in patients with Parietaria hay fever.

A double-blind, placebo-controlled study was conducted to evaluate the efficacy and safety of immunotherapy (IT) with a partially purified alginate-conjugated extract of Parietaria judaica (Conjuvac Parietaria, Dome/Hollister-Stier) in patients suffering from rhinoconjunctivitis caused by Parietaria pollen. Eighteen patients (10 women, 8 men, mean age 35 years) received active treatment and 17 (10 women, 7 men, mean age 42.5 years) received placebo. Actively treated patients had significantly lower nasal symptom/medication scores (running nose P = 0.0087 and sneezing P = 0.048) during the Parietaria pollen season. Significant decreases in specific skin (P < 0.01), nasal (P < 0.05), and conjunctival (P < 0.01) reactivity to the Parietaria extract and significant increases of specific IgG (P < 0.001), IgG1 (P < 0.001), and IgG4 (P < 0.001) in actively treated patients, but not in placebo, were found. IT was well tolerated, the active extract inducing five mild systemic reactions (four rhinitis and one urticaria) and placebo two (rhinitis). A significant correlation was found between low skin reactivity and high specific IgG (P = 0.0002) and IgG4 (P = 0.036). These findings indicate that IT with a partially purified P. judaica extract is an effective and safe treatment for Parietaria pollen allergy. The correlation between low immediate skin reactivity and high specific IgG and IgG4 suggests that, at least in the studied cutaneous model, these antibodies may exert a blocking effect.

Adjuvants, Immunologic↗

Unexpected phenotypes and predominant TCR V gene usage in random selected subjects.

The presence of a subset of T lymphocytes with an irregular phenotype has been identified in the peripheral blood of 22 subjects, selected among more than 5000 individuals evaluated for peripheral blood lymphocyte subset distribution as part of a routine procedure. By Southern Blot Analysis 13 out of 14 of the analysed samples presented additional non-germline bands, indicative of monoclonal or oligoclonal T cell expansions. Moreover, the cytometric analysis showed that 7 out of 19 analysed samples were restricted for a subfamily of the TCR variable regions. Thus, lymphocyte subsets with phenotypic irregularities could represent the clonally driven expansion of otherwise normally subpopulations, which may be present in peripheral blood below the limit of detection of routine phenotypic analyses. Such clonal populations could exert a regulatory activity either on the pathogenetic mechanisms of the disease or in maintaining homeostasis in healthy people.

Adult↗

Lymphocyte subsets and natural killer cell activity in healthy old people and centenarians.

The contribution of the immune system to healthy aging and longevity is still an open question. For this reason, several immune parameters (T, B, and natural killer [NK] cell subsets; non-major histocompatibility complex [MHC]-restricted cytotoxic activities, ie, natural and redirected killing [RDK] activities) were studied in a total of 138 healthy subjects of different ages, from 4 to 106 years of age, including 26 centenarians. The major age-related modifications were the following: (1) a decrease in the absolute number of T lymphocytes (CD3+), involving both CD4+ and CD8+ subsets, accompanied by a marked concomitant increase in the number of activated T cells (CD3+, HLA-DR+); (2) a marked decrease in the number of B lymphocytes (CD19+); and (3) an increase in the number of cells with markers of NK activity and of T lymphocytes able to mediate non-MHC-restricted cytotoxicity. These modifications linearly progressed with age and centenarians followed the trend, suggesting that their immune system did not escape the aging process. However, other immunohematologic parameters (number of red blood cells, platelets, and leukocytes) and important immune functions, such as cytotoxic activities (NK and RDK cell activities), were well preserved throughout life until the last decades of life. Unexpectedly, in apparently healthy middle-aged subjects, a decrease of cytotoxic activities was observed in comparison with those of both young controls and centenarians. In conclusions, our data suggest that in centenarians some immune responses are kept at a high level of efficiency, likely contributing to their successful aging. However, this selected group of people does not escape the aging process, as shown by the progressive derangement of a variety of immune parameters.

Adolescent↗

Cytofluorimetric identification of two populations of double positive (CD4+,CD8+) T lymphocytes in human peripheral blood.

Two different subsets of CD4+,CD8+ T lymphocytes have been identified in peripheral blood collected from normal subjects and from patients with different diseases. The subpopulations differed in the degree of CD4 and CD8 antigen expression. Hence, it was possible to distinguish by cytofluorimetric analysis cells with a low (dim) or with a high (bright) fluorescence intensity after the staining with anti-CD4 or anti-CD8 mAbs. CD4+dim,CD8+bright lymphocytes were found in patients with EBV-infectious mononucleosis and were present for less than a month. CD4+bright,CD8+dim T cells were observed in neoplastic patients as well as in healthy subjects and were continuously present in similar percentages over a long period of time (at the moment, about 3 years). Both the subpopulations expressed CD2, CD3, CD5 antigens and had an alpha beta-TCR, but did not express CD1a or CD7. Only CD4+dim,CD8+bright cells expressed HLA-DR antigen and the activation marker CD38, while only CD4+bright,CD8+dim lymphocytes expressed CD56 and CD57 molecules. The hypothesis may be put forward that these two subsets represent an effort of the immune system to cope with different requirements, i.e., of viral or neoplastic origin, while it is not clear the meaning of these cells in healthy subjects.

Adolescent↗

Increased cytokine production in mononuclear cells of healthy elderly people.

The production of cytokines during aging, except interleukin (IL)-2, has been neglected in humans. We measured the in vitro production of IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and IL-1 beta by peripheral mononuclear cells from selected healthy young (mean age 26.8 years) and aged (mean age 80.2 years) subjects. Significant increases of IL-6, TNF-alpha and IL-1 beta levels were found in mitogen-stimulated cultures from aged donors, occurring at 24 to 72 h after stimulation. No significant differences were observed for IFN-gamma production. Proliferative capability of cells stimulated with PHA was not impaired in aged subjects. Since the amounts of all cytokines studied were similar in unstimulated cultures from young and aged subjects, and also serum levels of TNF-alpha did not differ, these data indicate that the cellular machinery for the production of these cytokines is well preserved in aging, and also that cells from old people are able to up-regulate their production in response to appropriate stimuli. The increases in cytokine synthesis were not dependent on changes in the number of monocytes, nor were they related to the significant rise of CD45RO+, and the concomitant decrease of CD45RA+, occurring in both CD4+ and CD8+ lymphocytes from aged subjects. The increased production of pro-inflammatory cytokines by stimulated mononuclear cells of healthy aged subjects may be relevant to several aspects of age-associated pathological events, including atherosclerosis, osteoporosis, fibrosis and dementia.

Adult↗

Early phenotypic activation of circulating helper memory T cells in scleroderma: correlation with disease activity.

OBJECTIVES: The differential expression of several accessory/activation molecules (CD26, CD29, CD45RA, CD25, MLR4, HLA-DR) on peripheral blood CD4+ and CD8+ T lymphocytes in patients with scleroderma was compared with that in controls and patients with other connective systemic diseases to look for evidence of the involvement of T cells in the disease process of scleroderma. METHODS: The two colour expression of surface molecules by circulating T cells was analysed with a panel of monoclonal antibodies and flow cytometry in 17 patients with scleroderma, 10 patients with systemic lupus erythematosus, and five patients with rheumatoid arthritis, and the results compared with those for 10 normal controls. The two colour T CD4+ phenotype was further compared between patients with active and quiescent disease in these patients with scleroderma. The coexpression of surface molecules by CD4+ T cells was also analysed by three colour flow cytometry in eight patients with scleroderma. RESULTS: Patients with scleroderma showed increased CD4+CD26+ and CD4+CD25+ percentages and absolute numbers and decreased CD8+CD29+ percentages compared with controls. Moreover, a significant correlation between the higher CD4+CD26+ T cell percentage and absolute cell numbers with disease activity was observed. Most of the CD4+ peripheral blood T cells from patients with scleroderma showed the CD26+CD45RA- phenotype by three colour flow cytometry analysis. CONCLUSIONS: The distinctive pattern of early helper memory T cell activation in these patients with rapidly evolving scleroderma supports the role of a T cell mediated mechanism in the progression of scleroderma.

Adult↗

Oral challenge with alternative nonsteroidal antiinflammatory drugs (NSAIDs) and paracetamol in patients intolerant to these agents.

The reliability and safety of the oral challenge procedure were evaluated in the diagnosis and prevention of intolerance to nonsteroidal anti-inflammatory drugs (NSAIDs). 112 NSAID-intolerant patients were submitted to oral challenge with aspirin (acetylsalicylic acid), dipyrone, paracetamol, imidazole-hydroxybenzoate or nimesulide to confirm historic intolerance and to evaluate tolerance to other NSAIDs. A significant correlation was demonstrated between history of intolerance and the results of oral challenge in aspirin-intolerant patients (p < 0.001). Of 237 challenges with various NSAIDs and paracetamol in 101 patients, 19 challenges were positive and 2 patients developed anaphylactic shock. The ratio of positive: total challenges with alternative NSAIDs and paracetamol were as follows: 7 of 83 for paracetamol, 2 of 49 for imidazole-hydroxybenzoate and 0 of 30 for nimesulide. On the basis of these results, nimesulide was evaluated as an alternative NSAID in a second group of 284 NSAID-intolerant patients. Challenge with nimesulide elicited a positive response in 14 patients (in 6 patients the response was delayed), although adverse reactions were mild in all instances. In conclusion, a positive history of intolerance to a given NSAID is a sufficient reason to contraindicate its use even for diagnostic purposes, e.g. oral challenge. Oral challenge should therefore be restricted to the assessment of the tolerability of alternative NSAIDs. In the present study nimesulide appeared to be the safest currently available alternative in patients with NSAID intolerance.

Acetaminophen↗

IgE-mediated allergy from vegetable allergens.

Allergy to fresh fruits and vegetables is IgE-mediated. Its main clinical features are local, such as oral pruritus and swelling of lips and tongue but systemic symptoms such as urticaria, asthma, or anaphylactic shock may occur. Clinical associations with allergic rhinitis due to cross-reactive antigens of pollens and foods are frequent.

Adolescent↗

Selective deficiency of CD4+/CD45RA+ lymphocytes in patients with ataxia-telangiectasia.

Several immunological abnormalities have been observed in ataxia-telangiectasia (AT), the most consistent being defects of immunoglobulin isotypes, decreased T-cell numbers, and reduced proliferative responses to mitogens. We examined the distribution of T lymphocytes expressing distinctive surface Ag characteristic of "naive" (CD45RA+) and "memory" (CD29+, CD45RO+) T cells, in both CD4+ and CD8+ (bright and dim) lymphocytes from 13 AT patients, compared with healthy age-matched controls. We found that, irrespective of age, patients with AT had a severe deficiency of CD4+/CD45RA+ lymphocytes. This decrease accounted for the reduction of total CD4+ cells, since the absolute numbers of memory CD4+ cells were not significantly different in AT and in controls. Functional tests revealed poor proliferative responses to phytohemagglutinin and normal responses to soluble Ag (tetanus toxoid) in AT patients. These data fit with the distribution of naive and memory cells, which are known to respond predominantly to mitogens or to recall Ag, respectively. CD45RA molecules were normally expressed on CD8+ lymphocytes. This rules out a generalized defect of regulation or differential splicing as the cause of defective expression of CD45RA on CD4+ cells. The selective deficiency of CD4+CD45RA+ may provide a cellular basis for some functional T-cell abnormalities of AT patients. Furthermore, it might practically serve for an early, or even prenatal, diagnosis of this disease.

Adolescent↗

Changes in circulating B cells and immunoglobulin classes and subclasses in a healthy aged population.

The study of 87 adults of different ages, including 15 centenarians, selected for their healthy status, showed that profound changes of humoral immunity occur throughout life. In particular, a statistically significant age-related increase of the serum level of immunoglobulin classes (IgG and IgA but not IgM) and IgG subclasses (IgG1, 2 and 3, but not IgG4) was detected. A parallel age-related decrease of circulating B cells was also observed. The hypothesis of a complex derangement of B cell function and/or compartmentalization with age is put forward, together with the proposal that healthy centenarians (as representative of successful ageing) may be helpful in identifying the physiological age-related modifications of the immune system.

Adult↗