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Biomedical subjects

C Lombardo

Publications and source records attributed to C Lombardo.

At least 19 recordsLinked to original sources

Distribution of killer cell immunoglobulin-like receptors genes in the Italian Caucasian population.

BACKGROUND: Killer cell immunoglobulin-like receptors (KIRs) are a family of inhibitory and activatory receptors that are expressed by most natural killer (NK) cells. The KIR gene family is polymorphic: genomic diversity is achieved through differences in gene content and allelic polymorphism. The number of KIR loci has been reported to vary among individuals, resulting in different KIR haplotypes. In this study we report the genotypic structure of KIRs in 217 unrelated healthy Italian individuals from 22 immunogenetics laboratories, located in the northern, central and southern regions of Italy. METHODS: Two hundred and seventeen DNA samples were studied by a low resolution PCR-SSP kit designed to identify all KIR genes. RESULTS: All 17 KIR genes were observed in the population with different frequencies than other Caucasian and non-Caucasian populations; framework genes KIR3DL3, KIR3DP1, KIR2DL4 and KIR3DL2 were present in all individuals. Sixty-five different profiles were found in this Italian population study. Haplotype A remains the most prevalent and genotype 1, with a frequency of 28.5%, is the most commonly observed in the Italian population. CONCLUSION: The Italian Caucasian population shows polymorphism of the KIR gene family like other Caucasian and non-Caucasian populations. Although 64 genotypes have been observed, genotype 1 remains the most frequent as already observed in other populations. Such knowledge of the KIR gene distribution in populations is very useful in the study of associations with diseases and in selection of donors for haploidentical bone marrow transplantation.

Journal Article↗

Oral rush desensitization with tomato: a case report.

Adverse food reaction in which no immunological mechanism is demonstrated should be termed nonallergic food hypersensitivity or food intolerance. We present the case of a 12-year-old girl with a clinical history of abdominal pain, nausea, and general malaise after tomato intake which completely remitted with antihistamines. The patient underwent a complete allergy evaluation: skin prick tests, serum specific IgE and IgG4 tests to tomato, and double-blind placebo-controlled food challenge. Skin prick tests and specific IgE to tomato were negative while the food challenge was positive. At the end of the workup, the patient underwent an oral rush desensitizing treatment. At the end of the treatment the patient could eat a maintenance dose of 100 g of tomato daily with no side effects at all. This successful result suggests that the oral desensitizing treatment can be used in patients with nonallergic food hypersensitivity.

Child↗

Validity of a short insomnia questionnaire: the SDQ.

The SDQ is a brief self-report insomnia questionnaire, which permits the rapid evaluation of insomnia based on the DSM-IV and ICSD-R criteria. The SDQ was developed to provide a fast and valid instrument both for the pre-screening of subjects who complain of insomnia and for epidemiological studies based on standardized definitions of this sleep disorder. Two studies were carried out in order to assess the validity of the SDQ as a self-report measure of insomnia. In the first study the convergent validity of the SDQ was assessed with respect to the global score of the Pittsburgh Sleep Quality Index (PSQI) in a sample of general practitioners' patients. The second study assessed the sensitivity and the specificity of the SDQ in discriminating between insomniacs or normal sleepers in a sample of college students who were given an extensive sleep evaluation within an insomnia counseling program. The SDQ classifications have a good convergent validity with the global sleep quality scores of the PSQI and its classifications of students who complain of or who do not complain of problems of insomnia have a sensitivity of 95% and a specificity of 87%. Results indicate that the SDQ is a valid paper and pencil instrument to screen insomnia.

Adult↗

Internal consistency, convergent validity and reliability of a brief questionnaire on disordered eating (DEQ).

Clinical interviews are considered the gold standard for the evaluation of the specific psychopathology associated with eating disorders. However, there are situations in which brief but valid and reliable self-report questionnaires can be helpful. For this reason, we have developed a new questionnaire, called the DEQ (Disordered Eating Questionnaire), brief enough to be used in epidemiological screenings, that evaluates the frequency and intensity of disordered eating attitudes and behaviours within a time frame of three months and addresses face valid questions to the general population. The aim of this study was to evaluate the dimensionality, reliability and convergent validity of this questionnaire. The DEQ was filled in by Italian secondary school girls and boys, together with the Contour Drawing Rating Scale (CDRS) and with the Eating Attitudes Test (EAT-26). The results showed a single component that explain a portion of variance of around 36%. The reliability of the scale is highly satisfactory. The scale is also valid, since scores on the DEQ scale are significantly and highly correlated with body dissatisfaction, measured by the CDRS, with body mass inex (BMI) and with all the subscales of the EAT-26. As expected, there were gender differences, given that DEQ scores were higher in females than in males.

Adolescent↗

Positive patch tests to Euro coins in nickel-sensitized patients.

BACKGROUND: Many efforts have been made to prevent nickel allergy, the most frequent contact allergy in industrialized countries, by identifying acceptable limits of exposure. Even though coins are not covered by the EU Nickel Directive, some authors suggest that nickel release from coins during handling may elicit contact dermatitis in nickel-allergic people. OBJECTIVES: To evaluate sensitivity to nickel released from coins in nickel-allergic patients and to verify whether nickel release from the new Euro coins may elicit stronger cutaneous reactivity than from old Italian lire coins. METHODS: Twenty-five nickel-allergic patients were patch tested with 1- and 2-Euro coins, 1-, 2- and 50-Euro cent coins, and 100 and 500 Italian lire coins. Ten healthy nonnickel-allergic control individuals were also tested. RESULTS: Nineteen patients had positive patch tests to 1- and 2-Euro coins. One was also positive to 1- and 2-Euro cent coins, four to 50-Euro cent coins, and 13 to the 500-lire coin. None had a positive patch test to the 100-lire coin. The number and degree of positive patch tests to coins were related to nickel content. CONCLUSIONS: Euro coins may be potentially more dangerous than old Italian coins. Coins containing little or no nickel should be chosen for coinage to prevent sensitization and to avoid exacerbation of contact dermatitis in nickel-allergic patients.

Adolescent↗

Demonstration of an IgE-mediated immunological pathogenesis of a severe adverse reaction to gadopentetate dimeglumine.

In this case report, the authors, after reviewing the literature data about contrast agents in Magnetic Resonance Imaging (MRI) and correlated problems, investigate the immunological mechanism of an adverse reaction to gadopentetate dimeglumine (Gd-DTPA), in order to demonstrate an IgE-mediated immunological pathogenesis. The case of a patient who underwent MR imaging in our hospital was studied. During, and after, the MR examination with Gd-DTPA the patient showed local warmth/pain to the external genitalia and to the face, tachycardia, nausea, vomiting, diarrhea, uterine cramps, and diffuse cutaneous rash. Skin tests (intradermal) and the passive transfer test according to Prausnitz and Küstner were positive, suggesting the involvement of an I-type allergy (IgE-mediated) mechanism. In this paper, we demonstrate that the adverse reactions to Gd-DTPA can be supported by an immunological mechanism.

Adult↗

An immunogenetic map of Lombardy (Northern Italy).

For this study we consulted the Bone Marrow Donors' Registry of Lombardy (Italy) and analyzed 43937 HLA-A,B phenotypes and 13922 HLA-A,B,DR phenotypes. We estimated the HLA-A,B and HLA-A,B,DR haplotype frequencies via the maximum-likelihood method. We analyzed the genetic structure of the 11 provinces of Lombardy by means of Principal Component Analysis and Correspondence Analysis, and estimated the variety of the different haplotypes at provincial level and the percentage of unique phenotypes at village level. We found 11189 different HLA-A,B phenotypes, 661 different HLA-A,B haplotypes and more than 4000 different HLA-A,B,DR haplotypes. We identified 20 villages, in Western Lombardy, very rich in unique/rare phenotypes. Here we report a formula which allows the identification of a putative donor matched for two haplotypes with a recipient. This result may be of great importance for the genetic study of the population of Lombardy and, even more, for bone marrow transplantation programs.

Alleles↗

Analysis of circulating tumor DNA in plasma at diagnosis and during follow-up of lung cancer patients.

We evaluated whether the amount of circulating DNA in plasma could discriminate between lung cancer patients and healthy individuals and whether it is related to disease progression, and we analyzed the kinetics of plasma DNA in disease-free, surgically resected patients. Plasma DNA quantification and analysis of microsatellite alterations were performed in a consecutive series of 84 patients with non-small cell lung cancer, who were studied during follow-up, and 43 healthy controls. In patients, the mean values of plasma DNA concentration were higher than in controls even considering stage Ia patients. Sensitivity and specificity estimates were calculated as the area under the receiver operating characteristic curve (AUC-ROC) curve and showed a value of 0.844. Variations in DNA level and in microsatellite changes correlated with the clinical status of 38 patients monitored during follow-up. The data suggest that quantification and molecular characterization of plasma DNA in lung cancer patients are valuable noninvasive diagnostic tools for discriminating patients from unaffected individuals and for detecting early recurrence during follow-up.

Adult↗

Interaction of endostatin with integrins implicated in angiogenesis.

Endostatin, a fragment of collagen XVIII, is a potent antagonist of angiogenesis and inhibitor of tumor growth in mouse models. At present, the mechanism of action of endostatin is unknown. We show here that recombinantly produced human endostatin interacts with alpha(5)- and alpha(v)-integrins on the surface of human endothelial cells. We further demonstrate that the endostatin-integrin interaction is of functional significance in vitro, as we found that immobilized endostatin supports endothelial cell survival and migration in an integrin-dependent manner. Soluble endostatin in turn inhibits integrin-dependent endothelial cell functions, such as cell migration. Taken together, these results implicate integrins as potential targets for endostatin function and support the importance of integrins in endothelial cell biology and angiogenesis.

Angiogenesis Inhibitors↗

Simultaneous transduction of B7-1 and IL-2 genes into human melanoma cells to be used as vaccine: enhancement of stimulatory activity for autologous and allogeneic lymphocytes.

In order to construct an immunogenic cellular vaccine, we transduced three HLA-A*0201 human melanoma lines, selected for expression of classes I and II HLA, adhesion molecules and the T cell-defined melanoma antigens Melan/MART-1, gp100 and tyrosinase, with both interleukin-2 (IL-2) and B7-1 genes by the use of a polycistronic retroviral vector. The lines were selected to share only the HLA-A*0201 allele to avoid generation of strong alloreactivity in case of their multiple in vivo use in HLA-A*0201 + patients. Phenotypic and functional analysis of B7-1-IL2 transduced melanoma lines in comparison with B7-1 transduced and/or parental untransduced counterparts were then carried out. Tumor cells expressing either B7-1 or both genes did not change their original antigenic profile. From a functional point of view, expression of both genes in melanoma lines: (1) improved the response of anti-melanoma cytotoxic T lymphocytes (CTL) over singly transduced or untransduced melanoma cells when subthreshold levels of MHC-peptide complexes were expressed by melanoma cells; (2) conferred a distinct advantage in the ability to stimulate cytotoxicity and interferon-gamma release by autologous and/or HLA-A*0201-compatible allogeneic lymphocytes; (3) allowed the generation of a high number of specific CTL by in vitro stimulation of lymphocytes of HLA-A*0201-melanoma patients. Thus, B7-IL2 gene-transduced melanoma lines appear to display a high immunogenicity and could be used as vaccine in melanoma patients.

B7-1 Antigen↗

Effect of lifestyle, smoking, and diet on development of intestinal metaplasia in H. pylori-positive subjects.

OBJECTIVES: This study aimed to evaluate the influence of environmental and sociodemographic factors and the effect of smoking, alcohol, and dietary habits on the risk of gastric intestinal metaplasia (IM) in Helicobacter pylori-infected subjects. METHODS: The investigation was based on 2598 consecutive volunteer blood donors tested for the presence of antibodies against H. pylori from March 1995 to March 1997. Endoscopy with multiple biopsies was offered to all H. pylori-positive, symptomatic subjects. The presence or absence of IM was diagnosed by gastric biopsies. A serologically H. pylori-positive subject with gastric IM was defined as a case, whereas serologically H. pylori-positive subjects without IM were used as controls. All patients answered a detailed questionnaire collecting sociodemographic characteristics and smoking, alcohol drinking, and dietary habits. Odds ratios (ORs) and their 95% CIs were estimated by unconditional logistic regression, including terms for age and sex, to assess the association between the data collected and IM. RESULTS: Three hundred forty-four subjects with serological H. pylori infection and upper-GI symptoms underwent GI endoscopy, during which biopsies were taken for histological diagnosis. Histology revealed metaplasia in 74 subjects (21.5%). Incomplete IM was found in 37.8% of these cases. No significant associations were found between IM and anthropometric or sociodemographic factors. There was a significant association between age and IM (chi2 for trend, 6.67; p value, 0.009). Current smokers of over 20 cigarettes per day had a 4-fold risk of IM (OR, 4.75, 95% CI, 1.33-16.99). A 2-fold increased risk was found for high butter consumers (OR, 2.17; 95% CI, 1.14-4.11). No significant specific associations were found between the variables studied and complete or incomplete IM. CONCLUSIONS: This study found that smoking and high butter consumption may increase the risk of having gastric IM in H. pylori-positive subjects.

Adult↗

Hymecromone in the treatment of motor disorders of the bile ducts: a multicenter, double-blind, placebo-controlled clinical study.

Biliary dyskinesia is frequently encountered in clinical practice and is characterized by pain during or after meals. The present study was designed to assess the action of hymecromone in patients with motor disorders of the bile ducts. One hundred twenty-three patients (36 men and 87 women) were enrolled in the multicenter double-blind placebo-controlled study. The mean age was 60.3 years +/- 14.2 SD. Diagnosis was dyspepsia in 58 patients, dyskinesia in 59, cholelithiasis in five and hepatopathy in one. The patients were divided into two groups. One group (61 patients) was treated with hymecromone (300 mg tablets at a dosage of 1,200 mg/day, 2 tablets midday and evening) and another group (62 patients) was treated with placebo. Treatment lasted for 14 days. Control of dyspepsia and pain symptoms of biliary origin was more marked and constant with hymecromone than with placebo. By the end of the treatment, patients in the hymecromone group showed a 70.3% reduction in intensity of spontaneous abdominal pain, while the placebo group showed a 43.8% reduction. Hymecromone was well accepted by the patients and judged to be effective by the investigator in 88.5% of patients treated. The possibility of using hymecromone in 300-mg tablets in the treatment of motor disorders of the bile ducts is thus confirmed.

Adolescent↗

T cell responses in colorectal cancer patients: evidence for class II HLA-restricted recognition of shared tumor-associated antigens.

Few cases of anti-colon cancer specific T lymphocytes have been described so far. Moreover, the majority of these effectors were generated in vitro by stimulating PBMC from patients or healthy donors with peptides that were derived from proteins expressed and/or secreted by colon cancer tissue such as CEA, Mucin or Her-2/neu. The aim of our study was to evaluate the immunogenicity of colorectal carcinomas in an autologous setting. We exploited the antigen processing and presentation capacity of dendritic cells (DC) to establish an in vitro autologous system that can bypass the need of obtaining cultured tumor cells. DC were generated from the adherent monocyte fraction of PBMC taken from stage II/III colorectal cancer patients. A single cell suspension was prepared by mechanical and enzymatic disruption of the surgical specimens immediately after resection. DC were loaded with autologous tumor lysate, obtained by repeated freezing and thawing, before being used as stimulators for autologous PBL. HLA-class II restricted T cells that recognize the autologous tumor could be generated in a proportion of patients. The fine specificity of the anti-tumor T cells indicates that differentiation as well as tumor restricted antigens are expressed in colon cancer and that these antigens can evoke a class II HLA-restricted response in an autologous setting. Altogether these findings may open a new perspective for a DC based vaccination of colon cancer patients.

Antigens, Neoplasm↗

Differential recognition of a BCR/ABL peptide by lymphocytes from normal donors and chronic myeloid leukemia patients.

The BCR/ABL oncogenic fusion protein transforms normal bone marrow stem cells into neoplastic cells. It has been shown that peptides derived from the junctional region of this oncogenic fusion protein can be recognized by human T-lymphocytes obtained from normal donors. In this study, we investigated the immunogenicity in patients with chronic myeloid leukemia (CML) of a 17 mer b3/a2 Bcr/abl peptide (B/A1), which was shown to induce proliferative responses in lymphocytes from normal donors. A total of 56 CML patients in chronic phase were studied. Twenty-two patients were studied at diagnosis without any treatment (group I). Fourteen patients were receiving IFN (group II), 14 patients were being treated with hydroxyurea (group III), and 6 patients were on different regimens (group IV). Patients were initially assessed for general immunological competence using both in vivo and in vitro assays. Patients were also selected for the expression of HLA-DR0401, the HLA specificity known to present peptide B/A1 to CD4 lymphocytes. With the exception of the six patients in group IV, the results of all these assays (in vitro phytohemagglutinin/tetanus toxoid responses, in vivo skin reaction to ubiquitous antigens) in CML patients did not significantly differ from those obtained in normal donors, thus excluding the presence of generalized immunosuppression. Eight patients with HLA-DR0401 and a b3/a2 type of fusion were identified and further studied. In these eight patients dendritic cells were obtained from adherent peripheral blood mononuclear cells and used to stimulate CD4 lymphocytes. No patient developed a specific response to the bcr/abl peptide, although patients' lymphocytes proliferated in response to a promiscuous tetanus toxoid peptide in all but one case. In contrast, response to the bcr/abl peptide was observed in seven of eight HLA-DR0401 healthy donors tested. These data suggest that immunocompetent, HLA-DR0401+ CML patients are unable to respond to peptide B/A1, at difference from healthy donors. The implication of these results for the immunotherapy of CML is discussed.

Cell Division↗