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Biomedical subjects

A Venuti

Publications and source records attributed to A Venuti.

At least 19 recordsLinked to original sources

Bovine papillomavirus E5 oncoprotein binds to the activated form of the platelet-derived growth factor beta receptor in naturally occurring bovine urinary bladder tumours.

Studies regarding the functions of the bovine papillomavirus (BPV) E5 oncoprotein in vivo are lacking and no E5-mediated mechanism underlying epithelial carcinogenesis is known. We have shown that BPV-2 DNA is present in the majority of naturally occurring urinary bladder tumours of cattle and that E5 is expressed in the cancer cells. Here we show that the interaction between the platelet-derived growth factor (PDGF) beta receptor and BPV E5, described in vitro in cultured cells, takes place in vivo in bovine urinary bladder cancers. In these cancers, E5 and PDGF beta receptor colocalize, as shown by confocal microscopy, and physically interact, as shown by coimmunoprecipitation. Furthermore, the PDGF beta receptor associated with E5 is highly phosphorylated, suggesting the functional activation of the receptor upon E5 interaction. Our results demonstrate, for the first time, that E5-PDGF beta receptor interaction occurs during the natural history of bovine urinary bladder tumours, suggesting an important role for E5 in carcinogenesis. Finally, the system provides a suitable animal model of papillomavirus-associated cancer to test therapeutic vaccination against E5. Successful bladder tumour regression would provide a valuable model for therapeutic vaccination against papillomavirus-associated tumours.

Adenocarcinoma↗

Spontaneous ocular squamous cell carcinoma in twin goats: pathological and biomolecular studies.

Ocular squamous cell carcinoma (OSCC) is a well-characterized tumour occurring spontaneously in cattle and other mammalian species but not previously reported in the goat. This report describes the histological features of well-differentiated OSCCs in twin goats. Biomolecular investigations led to the identification of Papillomavirus-related DNA sequences within the neoplastic ocular parenchyma of both animals, but immunohistochemical and ultrastructural studies failed to demonstrate viral particles. A putative role of Papillomavirus in the aetiology of OSCC is discussed, together with other possible causative factors.

Animals↗

Presence of HPV in head and neck tumours: high prevalence in tonsillar localization.

Human papillomavirus (HPV) seems to be involved in head and neck carcinogenesis. To investigate this association, viral presence and expression were analysed by polymerase chain reaction (PCR)-based methods and correlated to tumour localization, clinical-pathological aspects, and alcohol and tobacco exposure in 65 patients. HPV DNA was found in 16 cases (24.6%); the HPV types detected were: HPV16 (10 cases), HPV 6 (3 cases) HPV 33, 35, and 58 (one case each). The tonsil was the location with the highest HPV positivity (6/8, 75%). This percentage was significantly higher than that found in tumours from any other site (P<0.01). Viral transcripts of early regions were detected in all HPV16 positive tumours. HPV status was not related to age, gender, tumour stage or grade, and use of alcohol and/or tobacco. The results suggest that HPV16 is actively involved in the genesis of a subset of head and neck cancers and that the tonsillar localization may be considered a hot spot for viral transformation.

Adult↗

Prevalence of sensitization to Cupressus sempervirens: a 4-year retrospective study.

In the last few years Cupressus sempervirens has been identified as the cause of an increasing number of cases of late winter-early spring pollinosis in Mediterranean countries. We conducted a 4-year retrospective study of a large group of subjects with documented allergic respiratory disease in order to determine the prevalence, clinical significance and annual rate of sensitization to C. sempervirens pollen. Anamnestic data and skin prick tests (SPT) with common aeroallergens and C. sempervirens extract were collected from 1397 subjects (712 male and 685 female) resident in Latium, a region in central Italy, with complaints related to upper- or lower-respiratory-tract disorders or conjunctival disease. Two hundred and forty-three subjects (17.4%) showed positive results to C. sempervirens extract: 47 (19.3%) of them were monosensitized. The annual sensitization rate of SPT positivity to C. sempervirens varied from 7.2% in 1995 to 22% in 1998. All the subjects monosensitized to cypress pollen had symptoms from January through April. Our study suggests that sensitivity to C. sempervirens is responsible for respiratory symptoms in an increasing percentage of subjects. Further studies are needed to determine its frequency at the national level.

Adolescent↗

Egg yolk antibodies against the E7 oncogenic protein of human papillomavirus type 16.

The E7 oncoprotein is the major transforming protein of Human Papillomavirus type 16 (HPV16) and the most abundant in cervical neoplasia. In this study we report the production of polyclonal antibodies to HPV16 E7 in rabbits and hens. The produced antibodies recognised the denatured and native form of HPV16 E7 protein by Western Blot, and immunoprecipitation. Epitope mapping demonstrated that hen antibodies reacted with a greater number of antigen determinants than the rabbit antibodies. In immunocytochemistry only hen antibodies were able to localize the E7 protein in a HPV positive cell line and in the high-grade squamous intraepithelial lesions, suggesting their possible usefulness in the screening of clinical samples.

Animals↗

Food-dependent exercise-induced anaphylaxis: clinical and laboratory findings in 54 subjects.

BACKGROUND: In some subjects, specific foods trigger anaphylaxis when exercise follows ingestion (specific food-dependent exercise-induced anaphylaxis, FDEIAn). Skin test and/or RAST positivity to foods suggest an IgE-mediated pathogenic mechanism. Others suffer from anaphylaxis after all meals followed by exercise, regardless of the food eaten (nonspecific FDEIAn). We sought to identify the culprit foods with a diagnostic protocol. METHODS: We collected detailed histories and performed skin prick tests (SPT) with 26 commercial food allergens, prick plus prick tests (P+P) with 15 fresh foods (including 9 assessed with SPT), and RAST for 31 food allergens. Treadmill stress tests were administered after a meal without any positive food (food plus exercise challenge, FEC). RESULTS: Among the 54 patients, 6 could not recall any suspect food. The other 48 suspected a specific food in at least one episode. The most frequent were tomatoes, cereals and peanuts. Fifty-two subjects were positive to at least one food (22 to more than 20), whereas 2 showed no positive results. All suspect foods were positive. SPT, P+P and RAST displayed different degrees of sensitivity. Each test disclosed some positivities not discovered by others. Two subjects reacted to FEC. Overall, 48 patients probably had specific FDEIAn and the other 6 nonspecific FDEIAn. CONCLUSION: It is useful to test both in vivo and in vitro an extensive panel of foods. Avoidance of foods associated with skin test and/or RAST positivity for at least 4 h before exercise has prevented further episodes in all our patients with specific FDEIAn.

Allergens↗

The pagetoid variant of urothelial carcinoma in situ of urinary bladder in a cow.

A case of urothelial carcinoma in situ of urinary bladder is reported in a 10-year-old cow naturally grazing on bracken-infested land. The cow suffered from enzootic hematuria for more than 5 years. The presence of bovine papillomavirus type 2 (BPV-2) DNA sequences was detected by polymerase chain reaction. The carcinoma in situ was characterized by the presence of anaplastic cells with amphophilic cytoplasm and pleomorphic nuclei containing granular, irregularly dispersed chromatin. Focal areas within the tumor contained large isolated and/or clustered cells. These cells had pale acidophilic cytoplasm, large nuclei with single or multiple nucleoli, and well-defined borders resembling Paget's cells. Immunohistochemically, all malignant cells were negative for vimentin and S-100 and positive for cytokeratins. In addition, normal and neoplastic cells expressed fragile histidine triad (FHIT) protein; surprisingly, some pagetoid cells did not. FHIT, the tumor suppressor gene at 3p14.2, encodes a protein of 147 amino acids (16.8 kd) with diadenosine triphosphate hydrolase activity and is a common target of deletions in human cancers of epithelial origin. Antibody to laminin detected a continuous epithelial basement membrane, thus clearly showing that neoplastic changes were limited to urothelial cells without invading stromal tissue. To our knowledge, this is the first report of an unusual pattern of spread of urothelial carcinoma in situ in a cow.

Animals↗

Nasal immunotherapy at constant dosage: a double-blind, placebo-controlled study in grass-allergic rhinoconjunctivitis.

A preliminary open study showed that intranasal immunotherapy can be administered with a constant dosage scheduling, with good safety and efficacy. In the present study the efficacy of constant dosage intranasal immunotherapy has been evaluated on 43 grass-allergic rhinitis patients according to a double-blind placebo-controlled design. The product employed for the study had a formulation in powder, and was administrated by a nasal insufflator. Clinical efficacy was evaluated for each symptom, taking into consideration the severity of the symptom in relation to its frequency. Sneezing, rhinorrea, nasal blockage, eyes itching, and drug consumption were significantly improved in active-treated patients compared to placebo-treated. The safety of this treatment was good, the only adverse events observed being some local and mild symptoms. This immunotherapy was well-tolerated and easy to handle by the patients by self-administration.

Adolescent↗

Physical state and expression of human papillomavirus in laryngeal carcinoma and surrounding normal mucosa.

Epidemiologic and biomolecular evidence suggests that human papillomavirus (HPV) infection may be associated with the development of head and neck cancers. To clarify the role of HPV in larynx carcinoma, 25 patients were studied for the presence of viral DNA, possible virus integration into the cellular genome, and viral expression both in neoplastic tissues and in neighbouring normal mucosa. Twelve of 25 patients with neoplasia (48%) showed negative results for HPV sequences, and 13 (52%) showed positive results. Among the latter group of patients, seven were HPV-16 positive, five were HPV-6, and one was HPV-45. No multiple infections were detected. The physical status of the HPV genome was analysed by three methods: polymerase chain reaction (PCR), bidimensional agarose gel electrophoresis, and in situ hybridisation. Viral integration into the host genome occurred in 43% of cases of HPV-16 and in 20% of cases of HPV-6. Viral RNA expression was detected by reverse transcription-PCR only in HPV-16-positive tumours. The pattern of expression was consistent with an active role of HPV in cellular transformation. In conclusion, the present work suggests that HPV infection may be involved in some cases of laryngeal carcinoma. However, the transformation mechanisms might be different from those currently accepted for anogenital cancers.

Adult↗

Role of endothelin-1 in neovascularization of ovarian carcinoma.

Endothelin-1 (ET-1) is overexpressed in ovarian carcinomas and acts, via ET(A) receptors (ET(A)R), as an autocrine growth factor. In this study we investigate the role of ET-1 in the neovascularization of ovarian carcinoma. Archival specimens of primary (n = 40) and metastatic (n = 8) ovarian tumors were examined by immunohistochemistry for angiogenic factor and receptor expression and for microvessel density using antibodies against CD31, ET-1, vascular endothelial growth factor (VEGF), and their receptors. ET-1 expression correlated with neovascularization and with VEGF expression. The localization of functional ET(A)R and ET(A)R mRNA expression, as detected by autoradiography and in situ hybridization, was evident in tumors and in intratumoral vessels, whereas ET(B)R were expressed mainly in endothelial cells. High levels of ET-1 were detected in the majority of ascitic fluids of patients with ovarian carcinoma and significantly correlated with VEGF ascitic concentration. Furthermore ET-1, through ET(A)R, stimulated VEGF production in an ovarian carcinoma cell line, OVCA 433, by an extent comparable to hypoxia. Finally, conditioned media from OVCA 433 as well as ascitic fluids caused an increase in endothelial cell migration and the ET-1 receptor blockade significantly inhibited this angiogenic response. These findings indicate that ET-1 could modulate tumor angiogenesis, acting directly and in part through VEGF.

Adenocarcinoma↗

Tolerability of meloxicam in patients with histories of adverse reactions to nonsteroidal anti-inflammatory drugs.

BACKGROUND: Adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are frequent, particularly among patients with chronic urticaria or asthma. The need to identify an alternative drug that is safe and reliable is a common problem in clinical practice. OBJECTIVE: To assess the tolerability of meloxicam, a new NSAID that selectively inhibits the inducible isoform of cyclooxygenase, in a group of NSAID-sensitive patients. PATIENTS AND METHODS: We studied 177 patients who had suffered adverse reactions to one or more NSAIDs. Cutaneous reactions were reported by 83.1% of the subjects (urticaria in 55, angioedema in 52, urticaria/angioedema in 39, and maculopapular rash in 1), respiratory symptoms by 3.9%, both cutaneous and respiratory symptoms by 9%, Stevens-Johnson's syndrome by 2.3%, and anaphylactoid reactions by 1.7%. All subjects underwent a single-blind, placebo-controlled oral challenge with divided therapeutic doses of meloxicam (1.9 mg + 5.6 mg 1 hour later = cumulative dose 7.5 mg). RESULTS: Positive reactions were observed in only two cases (1.1%), both manifested exclusively by cutaneous symptoms (urticaria/angioedema in one case and maculopapular rash/facial edema in the second). CONCLUSION: Meloxicam seems to be well tolerated by NSAID-sensitive subjects whose reactions are manifested by urticaria/angioedema. Additional study is needed for a more complete assessment of its tolerability in patients with aspirin-induced asthma and other severe manifestations of NSAID sensitivity.

Adolescent↗