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Biomedical subjects

O Rossi

Publications and source records attributed to O Rossi.

At least 37 records · Page 2Linked to original sources

Chromosomal assignment of human O6-methylguanine-DNA-methyltransferase gene by hamster-human somatic cell hybrids.

Using an in vitro assay to measure O6-methylguanine-DNA-methyltransferase (MT) activity in cell extracts from a panel of human-hamster cell hybrids, we were able to locate the human MT gene on chromosome 10. Chinese hamster cells have little or no MT activity and the presence of human chromosome 10 was a necessary condition for MT activity in cell hybrids. In some cell hybrids carrying chromosome 10, however, MT activity was not higher than that of hamster cells. As an explanation for this result, genetic determinants repressing MT expression and/or activity might be present in other human chromosomes carried by MT-negative cell hybrids. Partial hyperploidy of the hamster karyotype, variable activity of the parental human cell lines and changes during subculturing of the cell hybrids might also account for the lack of enzymatic activity in chromosome 10 containing hybrids.

Animals↗

O6-alkylguanine-DNA alkyltransferase activity in human brain tumors.

The O6-alkylguanine-DNA alkyltransferase (AT) activity in different kinds of human brain tumors was investigated. Twenty-seven brain tumors were analysed. Twenty-five of them showed proficient AT activity with values ranging between 20 and 722 fmol AT/mg protein. The two AT-deficient tumors observed were an oligodendroglioma and an astrocytoma. The relationship between the different histological kinds of tumor, with respect to the AT activity was: meningeomas greater than sarcomas greater than glioblastomas greater than astrocytomas greater than oligodendrogliomas greater than neurinomas greater than lymphomas. The proposal of Kohn (DNA filter elution methods in anticancer drug development. In: Concepts, Clinical Developments, and Therapeutic Advances in Cancer Chemotherapy. Editor: F.M. Muggia. Martinus Nijhoff Publishers, Boston) to confine treatments with alkylating antineoplastic agents to AT-deficient tumors, is discussed.

Animals↗

[Possible role of 06-methylguanine-DNA-transferase in the response of patients with primary tumor of the brain to chemotherapy using chloro-ethyl-nitroso-urea: results of a current study].

We have started a study to measure the MT activity in surgical specimens from high grade human malignant gliomas, with the dual aim to (i), know whether lack of activity can be demonstrated in these tumors, and (ii), relate the measured levels of MT to the histology of the tumors and to the response of patients to chemotherapy with 1-(2-Chloroethyl)-3-Cyclohexyl-1-Nitrosourea (CCNU). To date, 12 Gliomas have been assayed. In 11 tumors, MT activities ranging from 30 to 150 fmoles/mg protein have been measured. The only negative specimen derived from a patient who had received radiotherapy before surgery. At the present stage of the study, therefore, we have no unequivocal evidence for the existence of MT-deficient Gliomas.

Astrocytoma↗

[Recent findings in the pathogenesis of bronchial asthma].

The latest discoveries about the pathogenesis of asthma are reported with emphasis on new data concerning the discovery of factors capable of controlling the production of IgE antibodies. The mechanisms implicated in early and late phase reactions are then discussed. In addition, the relationships between neuropeptides and chronic inflammation are described. Finally, the role of active substances produced by the bronchial epithelium on the induction and maintenance of bronchial inflammation is reviewed.

Asthma↗

[A new H1-blocking antihistamine. Critical review of pharmacological and clinical studies].

Astemizole is a long-acting antihistamine that blocks the H1 receptors. Thanks to its long-acting effect, symptoms can be controlled by a single daily dose. Its efficacy in the treatment of seasonal and permanent allergic rhinitis has been demonstrated in many studies in which it was compared with other antihistamines. It has also proved useful in the treatment of allergic conjunctivitis and chronic urticaria. Though a tendency to increased appetite and slight weight gain after prolonged use has been noted in some patients, astemizole is not sedative and has no anticholinergic effect in the standard therapeutic doses.

Animals↗

Effect of in vitro irradiation and cell cycle-inhibitory drugs on the spontaneous human IgE synthesis in vitro.

The in vitro effects of radiation, diterpine forskolin (FK), and hydrocortisone (HC) on the in vitro spontaneous IgE synthesis by peripheral blood B-lymphocytes from atopic patients were investigated. Without affecting cell viability, in vitro irradiation inhibited in a dose-dependent fashion de novo IgE synthesis in vitro by B cells from all patients examined with a mean 40% reduction of in vitro IgE product after treatment with 100 rads. In contrast, the in vitro IgE production by the U266 myeloma cell line was unaffected, even by irradiation with 1600 rads. The addition to B cell cultures from atopic patients of FK consistently resulted in a dose-dependent inhibition of the spontaneous IgE production in vitro. The addition to cultures of 10(-5) and 10(-6) molar concentrations of HC was also usually inhibitory, whereas lower HC concentrations were uneffective or even enhanced the spontaneous in vitro IgE synthesis. When 10(-6) molar concentrations of both HC and FK were combined in culture, a summation inhibitory effect on the spontaneous IgE synthesis was observed. In contrast, neither FK nor HC had inhibitory effect on the in vitro spontaneous IgE synthesis by the U266 myeloma cell line. The spontaneous in vitro IgE synthesis by B cells from patients with Hodgkin's disease, demonstrating high levels of serum IgE, was strongly reduced or virtually abolished after patients underwent total nodal irradiation to prevent the spread of the disease. In addition, the in vitro spontaneous IgE synthesis by B cells from atopic patients was markedly decreased or abolished by in vivo administration of betamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Atropine does not inhibit late asthmatic responses induced by toluene-diisocyanate in sensitized subjects.

To determine whether early and/or late asthmatic responses induced by toluene diisocyanate (TDI) are caused by a reflex mechanism involving stimulation of muscarinic receptors, we studied the effect of the muscarinic antagonist atropine on early and late airway response induced by TDI. A preliminary study was conducted in asthmatics to assess whether the selected dose of atropine provided adequate muscarinic blockade. On different days we measured the provocation dose (in milligrams) of carbachol causing a 15% decrease in FEV1 (PD15FEV1) without and with atropine premedication (0.008 or 0.012 mg/kg subcutaneous atropine 30 or 90 min before carbachol challenge test). We found that 0.008 to 0.012 mg/kg subcutaneous atropine increased the PD15FEV1 carbachol by 6- to 10-fold, inducing a consistent and prolonged decrease in nonspecific bronchial hyperresponsiveness to cholinergic agent. Then we examined 10 subjects with a history of sensitization to TDI in 2 sets of experiments. In the first set of experiments, we studied the subjects before and after exposure to TDI (0.04 ppm; 30 min) after no treatment. In the second set of experiments, carried out 1 to 2 wk later, we repeated the same procedure after treatment with atropine (0.008 to 0.012 mg/kg atropine sulfate administered subcutaneously 30 min before TDI challenge, and then at 90-min intervals after TDI exposure); all patients showed symptoms of atropine effect (dryness of mouth, cycloplegia, increased heart rate).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Skin reactivity and specific IgE levels in the evaluation of allergic sensitivity to common allergens for epidemiological purposes.

An investigation was conducted to test the validity of the skin-prick test (SPT) with eleven common allergens (Lofarma series proposed by Italian National Research Council for epidemiological studies) as a method for predicting the presence of specific antibodies in serum. The relationship between SPT, evaluated by two different methods (MWD = mean weal diameter, AHWR = allergen histamine weal ratio), and specific IgE levels (RAST) has been investigated in 101 patients tested consecutively for suspected allergic disease. Sensitivity, specificity and overall efficiency were assessed for different criteria of SPT positivity (greater than or equal to 4 mm or greater than or equal to 5 mm using MWD; ++ or using AHWR). For pollens and moulds, a weal diameter greater than or equal to 5 mm gave better results than 4 mm, whereas for mites a MWD greater than or equal to 4 mm showed a better sensitivity and overall efficiency than 5 mm. Danders showed low sensitivity when either 5 or 4 mm criterion was considered. AHWR evaluation gave no better results, except for animal danders. Correlation coefficients between weal size and RAST class showed a good relationship for mites and pollens using both methods of SPT evaluation; a moderate relationship was observed with MWD criterion for moulds and with AHWR for danders. We conclude that a weal diameter greater than or equal to 5 mm can be assumed to to predict RAST positivity for pollens and moulds, and for mites, a weal greater than or equal to 4 mm can be a more accurate criterion.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

Specific bronchial reactivity to toluene diisocyanate: relationship with baseline clinical findings.

One hundred and fourteen subjects with asthma induced by toluene diisocyanate were identified and the pattern of their bronchial responses to challenge with toluene diisocyanate was studied. An occupational type specific bronchial provocation test with toluene diisocyanate (10-25 parts per thousand million for 10-15 minutes) elicited an immediate response in 24, a late response in 50, and a dual response in 40 patients. Subjects with a dual response showed at diagnosis a longer duration of symptoms and a greater prevalence of airway obstruction; in these subjects FEV1 (percentage of predicted value) was lower than in subjects with immediate or late reactions to toluene diisocyanate. The percentage of current smokers and ex-smokers was significantly lower in subjects with a late response (26%) than in subjects with immediate or dual responses (56% and 57% respectively). In 27 of the 114 subjects a non-specific challenge test with methacholine was performed and subjects with dual responses showed greater non-specific bronchial hyperresponsiveness than the other groups. These results suggest that a dual response to specific challenge in bronchial asthma related to toluene diisocyanate may be associated with more severe disease than other types of response, as assessed by duration of symptoms, baseline airway obstruction, and non-specific bronchial hyperresponsiveness. The high prevalence of non-smokers and low prevalence of smokers in the group with a late response to specific challenge is so far unexplained.

Adult↗

Specific bronchial reactivity to toluene diisocyanate: dose-response relationship.

20 patients with toluene diisocyanate (TDI)-induced asthma were examined in order to assess their threshold of response to TDI during specific bronchial provocative tests (BPT). Specific bronchial hyperresponsiveness was evaluated by performing, on different days, specific BPT with increasing concentrations of TDI until a positive response was obtained; the threshold of response to TDI (low: 0.02-0.05 ppm; moderate: 0.1 ppm; high: 0.2-0.25 ppm) and the pattern of positive response were evaluated in comparison with some clinical features of the disease. The threshold of airway response to TDI was low in 9, moderate in 7 and high in 4 patients. No evident relationship was observed between the threshold of response to TDI and the pattern of positive response to the lower TDI concentration (immediate in 5, late in 8 and dual in 7 subjects) or other clinical features (duration of asthmatic symptoms, smoking habits, cessation of work, nonspecific bronchial hyperresponsiveness to methacholine); however, 6 out of 9 patients with low threshold had nonspecific bronchial hyperreactivity in comparison with 6 out of 11 patients with moderate or high threshold. In 10 out of 13 patients who performed two positive BPT with different TDI concentrations, the pattern of response was the same either at lower and at higher TDI concentrations; 3 subjects who had a late reaction at the lower concentration showed a dual reaction to the higher TDI concentration. A relationship between the degree of the specific bronchial reaction (% fall in FEV1 from baseline value) and TDI concentration during BPT was observed for the immediate reaction but not for the late reaction.

Asthma↗

[Bronchopneumopathy caused by wheat flour: analysis of clinical cases].

We studied 31 subjects exposed to wheat (mean work duration: 33 years) with chronic bronchopulmonary disease. 19 subjects complained of chronic cough and phlegm, 5 of symptoms of bronchoconstriction not associated to chronic cough and phlegm; 7 subjects complained of oculo-rhinitis. Subjects with symptoms of bronchoconstriction had a longer mean age and work duration than the other ones. Pulmonary function tests showed a slight decrease of mid-expiratory flow rate with respect to reference values. Skin reactivity to common allergens and to allergenic extracts of wheat flour and grain was low, but a relevant number of dubious responses (weal: 3-4 mm) to specific allergens was observed. Bronchial hyperresponsiveness to methacholine or bethanechol was observed in 17 out of 30 subjects, and a positive response to occupational-type specific bronchial provocative test (sBPT) was elicited in 10 out of 30 subjects. There was a low relationship between positive response to sBPT and symptoms of bronchoconstriction or skin reactivity to specific allergens. These observations suggest that a high prevalence of chronic bronchitis and/or chronic airway limitation is showed in workers long-term exposed to wheat flour, in front of a low prevalence of skin reactivity to flour and grain. Occupational-type sBPT might induce in these patients a non immunological positive response to wheat flour by means of a not completely known mechanism.

Adult↗

Embryotoxicity of benzo(a)pyrene and some of its synthetic derivatives in Swiss mice.

We have studied the teratogenicity of benzo(a)pyrene (BP), benzo(a)pyrene-4,5-oxide, and a racemic mixture of 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, a proximal metabolite and ultimate carcinogenic metabolite of BP, respectively, and of 6-methylbenzo(a)pyrene after direct injection into embryonal Swiss mice. The compounds were dissolved in acetone and trioctanoin (1:1) and injected at doses ranging from 0.4 to 16.0 nmol/embryo on days 10, 12, and 14 of development. The transplacental effects of BP given at the same gestational days and at comparable dose levels were also evaluated. The control groups received 0.5, 1.0, or 2.0 microliter/embryo of vehicle on days 10, 12, or 14 of pregnancy, respectively. The fetuses were examined when they were 18 days old. On the basis of gross external and internal malformations, 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene appeared to be the most potent embryotoxic and teratogenic compound tested, causing 85% of embryolethality and 100% of malformed fetuses in the group treated on day 10 of intrauterine development. There were 61 and 27% of malformed fetuses following 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene treatment on days 12 and 14 of gestation, respectively. The effects of this BP metabolite were very specific and malformations such as exencephaly, thoraco- and gastroschisis, phocomelia, and edema were found. The administration of BP (both transplacental and direct intraembryonal injection) and benzo(a)pyrene-4,5-oxide caused no significant increase of malformed fetuses in any of the developmental stages considered. 6-Methylbenzo(a)pyrene induced multiple malformations (among these a high percentage of protruding tongue) in 50, 46 and 31% of the fetuses treated on days 10, 12, and 14 of gestational age, respectively. These results combined with previous data concerning the induction of lung tumors by the tested compounds in 15-day-old Swiss mouse embryos, emphasize the requirement of a common metabolic derivative of BP to induce both teratogenesis and carcinogenesis in mice. Furthermore present data show that midgestation Swiss embryos are also highly sensitive to the 6-methyl derivative of BP.

Abnormalities, Drug-Induced↗

TDI-induced oculorhinitis and bronchial asthma.

A case of allergic oculorhinitis induced by toluene diisocyanate (TDI) exposure in a subject who two years later developed bronchial asthma due to TDI is described. A 55-year-old nonatopic spray painter developed symptoms of oculorhinitis two or three hours after direct occupational exposure to polyurethane varnish; at the first examination neither specific nor nonspecific bronchial hyperresponsiveness was present. Two years later the patient, who had remained in his job, developed episodic dyspnea, wheezing, and cough immediately after TDI exposure, with persistence of oculorhinitis; at this time a slight immediate-type response to a specific bronchial provocative test with polyurethane varnish and TDI was observed. Nonspecific bronchial hyperresponsiveness was mild. Specific IgE to TDI-HSA conjugate was present at both the first and second examinations. We conclude that, in some cases, TDI may cause "allergic" oculorhinitis and bronchial asthma, probably with an immunological IgE-mediated mechanism.

Asthma↗

[Respiratory pathology caused by exposure to solvents in the shoe industry: description of 3 clinical cases].

Clinical and functional respiratory features of three shoe factory workers exposed to organic solvents from glue or other adhesives are described. All subjects complained of chronic cough, dyspnea and wheezing when exposed to non specific bronchial stimuli, and showed a non specific bronchial hyperresponsiveness to methacholine; symptoms and bronchial hyperreactivity persisted some years after the cessation of work. In two cases the onset of the symptoms was ascribed to the occupational exposure to glue activators (containing usually a considerable percentage of chlorinated hydrocarbons as dichloromethane or methilenedichloride). We supposed that occupational exposure to large amounts of glue solvents in shoe factory might cause a chronic airway impairment with non specific bronchial hyperresponsiveness.

Adult↗

Follow-up study of patients with respiratory disease due to toluene diisocyanate (TDI).

The outcome of the respiratory symptoms, pulmonary function tests and bronchial hyperresponsiveness was studied in forty-seven workers with respiratory disease due to toluene diisocyanate (TDI) (twenty-seven asthmatic and twenty non-asthmatic subjects) after about 2 years from the first examination. Eight of twelve asthmatic subjects who left the industry after the first examination complained at the follow-up of dyspnoea and wheezing, but pulmonary function tests were unchanged; bronchial hyperresponsiveness decreased in three, but most were still positive to challenge test with bethanechol at the follow-up. Fifteen subjects who continued their exposure to TDI showed at the follow-up a significant decrease of the spirometric parameters and an increase of the bronchial hyperresponsiveness, and symptoms of chronic bronchitis were more frequent at the second examination. Non-asthmatic subjects, both exposed and non-exposed to TDI at the second examination, showed a significant decrease of the pulmonary function tests but no relevant changes in bronchial hyperresponsiveness. Our data suggest that stopping occupational exposure to TDI frequently did not produce an improvement of the TDI bronchial asthma, and persistence of the occupational exposure causes a more rapid decline in the respiratory function.

Asthma↗