Search PubMed⌕ Search

Biomedical subjects

M Romano

Publications and source records attributed to M Romano.

At least 361 records · Page 20Linked to original sources

Pulmonary metabolism of mutagens and its relationship with lung cancer and smoking habits.

The S-12 fractions of lung peripheral parenchyma obtained from 80 male individuals, aged 17-71 years, were assayed as blind samples for the ability either to convert promutagens into bacterial mutagens or to decrease the potency of direct-acting mutagens in the Ames reversion test. In this system, lung preparations were completely ineffective in activating an N-nitroso compound (i.e., N-nitrosomorpholine) and polycyclic aromatic hydrocarbons [i.e., 3-methylcholanthrene and benzo(a)pyrene] or their metabolites [i.e., 3-hydroxy-benzo(a)pyrene and benzo(a)pyrene-trans-7,8-diol]. They yielded a borderline and sporadic activation of a cigarette smoke condensate, and a weak but frequent activation of an aromatic amine (i.e., 2-aminofluorene), of a heterocyclic amine (i.e., 2-amino-3,4-dimethylimidazo[4,5-f] and of a diamide (i.e., cyclophosphamide). The pulmonary metabolism was more oriented in the sense of detoxification, as shown by the consistent decrease of potency of direct-acting mutagens, including a metal (i.e., sodium dichromate), an acridine and nitrogen mustard derivative (i.e., 2-methoxy-6-chloro-9-[3-(2-chloromethyl)aminopropylamino]acridine or ICR 191), an epoxide (i.e., epichlorohydrin) and an N-oxide (i.e., 4-nitroquinoline-N-oxide). As assessed by means of a numerical score quantifying the variation of mutagenicity, a marked interindividual variability (up to 20-fold) was detected in the ability of lung specimens to affect the mutagenicity of test compounds. Such variability was not significantly related to the protein concentration of S-12 fractions, nor to the age of the patients under scrutiny, who during hospitalization were on normal institutional diets and did not receive any special drug treatment. The only significant difference between 20 noncancer and 60 lung cancer patients, irrespective of the histological type, was a decreased activation of cyclophosphamide in the latter group. Probably due to the high prevalence of smokers among lung cancer patients, a significantly decreased activation of cyclophosphamide was also observed in the group of smokers. Smoking habits were associated with a stimulation of detoxifying mechanisms which, in agreement with the results of a previous study with human alveolar macrophages (F. L. Petrilli et al., J. Clin. Invest., 77:1917-1924, 1986), was significant in the case of sodium dichromate. Such effect was further enhanced by considering only individuals smoking during the last 24 h before collecting lung specimens, and under these conditions it became significant also for ICR 191.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Metabolism of mutagens and carcinogens in woodchuck liver and its relationship with hepatitis virus infection.

Thirty-six wild-caught woodchucks (Marmota monax) were characterized according to sex, weight, trapping locality, liver pathology, and serum or hepatic markers of woodchuck hepatitis virus. Liver subcellular fractions were assayed for microsomal cytochromes P-450, aryl hydrocarbon hydroxylase, glutathione, cytosolic enzymes involved in its metabolism (glutathione S-transferase, glutathione peroxidase, and glutathione reductase), in the hexose monophosphate shunt (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), NADH- and NADPH-dependent diaphorases, and DT diaphorase. Moreover, liver postmitochondrial fractions were assayed for their ability to activate procarcinogens [i.e., a tryptophan pyrolysate product, aflatoxin B1, 2-aminofluorene, and trans-7,8-dihydrobenzo(a)pyrene] to mutagenic metabolites in the Ames reversion test and to decrease the activity of direct-acting mutagens [i.e., 4-nitroquinoline N-oxide, 2-methoxy-6-chloro-9-[3-(2-chloroethyl)aminopropylamino]acridine X 2HCl, and sodium dichromate]. A considerable interindividual variability in metabolism was observed among the examined woodchucks. Some of the investigated parameters were more elevated in virus carriers, especially in those suffering from chronic active hepatitis, but only a few of the recorded differences (i.e., oxidized glutathione reductase and NADPH-dependent diaphorase) were statistically significant. The comparison of the monitored activities in woodchucks and in other rodent species (rat and mouse) led to the conclusion that the liver metabolism of mutagens and carcinogens in woodchucks is more oriented in the sense of activation, while detoxification mechanisms are more efficient in rats and mice.

Animals↗

Increased percentage of activated Ia+ T lymphocytes in peripheral blood of neonates following exchange blood transfusion.

The expression of Ia-like antigens in peripheral blood T lymphocytes from newborns receiving postnatal total blood exchange was analyzed. A significantly increased percentage of Ia-positive T lymphocytes (Ia+ T cells) was observed 2 days after postnatal transfusion with total blood in comparison to data observed on Days 0, 5, and 15. Ia+ T cells were also significantly higher than in normal control newborns tested in the same period. When newborns received the blood exchange with irradiated total blood or with leukocyte-depleted blood, no increase in Ia+ T cells was observed and the percentage of these cells remained in the normal range (1-7%) on all the days tested (0, 2, 5, 15 days). For easy identification of the origin of Ia+ T cells, sex-incompatible blood was used for exchange, and a karyotype analysis was carried out for the detection of the Y chromosome on Ia+ T cells separated from peripheral blood on Day 2 and then cultured with interleukin 2 (IL-2) for 48 hr. It was thus established that Ia+ T cells were not of donor origin. Simultaneously with the expression of Ia-like antigens, host T cells also carried the interleukin-2 receptor (TAC). An allogeneic response, comparable to a host-versus-graft reaction, was probably responsible for the activation of T cells 2 days after total blood exchange in newborns.

Exchange Transfusion, Whole Blood↗

DNA synthesis, mitotic index, drug-metabolising systems and cytogenetic analysis in regenerating rat liver. Comparison with bone marrow test after 'in vivo' treatment with cyclophosphamide.

Rat-liver cells can be used to reveal "in vivo" clastogenic activity of indirect mutagens, provided that they are stimulated to divide by partial hepatectomy. In order to characterize the rat-liver metabolic capacity in such experimental conditions, several biochemical parameters were measured during the first 54-66 h of liver regeneration in Sprague-Dawley male rats, subjected to a partial hepatectomy. The levels of cytochrome P-450, the activities of styrene monooxygenase, epoxide hydrolase and glutathione-S-epoxide transferase were chosen as markers. All the enzymatic activities and the level of cytochrome P-450 decreased during the first 12 h after the hepatectomy to about 50% of the activities of the sham-operated rats considered as controls. Subsequent recovery of the metabolic capacity was not observed. DNA synthesis and the mitotic index were measured to find the most suitable time for metaphase analysis. DNA synthesis and the number of metaphases were maximal at, respectively, 22-25 and 28-31 h after partial removal of the liver. The sensitivity to clastogenic damage induced by "in vivo" treatment with cyclophosphamide (CPA) was assayed in regenerating liver cells by chromosome-aberration analysis. Different doses, ranging from 5 to 30 mg/kg b.w., were given i.p. to the rats 17 h before or 7 h after partial hepatectomy. Liver cells were collected 31 h after surgery. Clastogenic damage was greater when the drug was administered to the animals after the hepatectomy (24 h of exposure) than before (48 h of exposure). The sensitivity to CPA-induced damage was compared with a bone marrow cell test carried out on non-hepatectomized rats treated in the same way. The results indicated that in these conditions regenerating liver cells are more sensitive than bone marrow cells to the induction of chromosome aberrations by CPA.

Animals↗

Effect of somatostatin on salivary secretion in man.

Intravenous infusion of pentagastrin increases salivary secretion progressively at doses from 1 to 4 micrograms/kg body weight/h. Pentagastrin also stimulates salivary secretion of amylase. Simultaneous administration of somatostatin, at the dose that inhibits gastric secretion of pentagastrin-stimulated HCl, blocks the effect of pentagastrin on salivary flow, while it does not reduce the amylase concentration. The data suggest that different mechanisms underlie the effects exerted by pentagastrin on salivary flow and on the concentration of amylase in saliva.

Adult↗

Amiodarone treatment in cardiac preexcitation syndrome: use of signal averaged electrocardiogram.

Amiodarone effectiveness to prevent reentrant arrhythmia in Wolff-Parkinson-White (WPW) syndrome is well known. Authors tried to evaluate the results of long-term therapy in a group of 11 patients (mean age 39 +/- years) suffering from WPW syndrome. Before amiodarone treatment, a conventional ECG and a high resolution ECG (a new noninvasive technique) were performed in order to define Hisian activity. After 50 days of therapy (600 mg daily for the first week, 400 mg daily for the second week, 200 mg daily for 5 days in the following period), a second recording revealed the evidence a a lengthening of PR segment (p less than 0.05) and a disappearance of delta wave (1 patient) and arrhythmia. Before treatment, His deflection was defined only in 2 patients. After amiodarone therapy the H-V time was clearly evaluated in 9 patients. Probably the drug has induced a lengthening of AV node refractoriness and primarily an increase of accessory pathway refractoriness.

Adolescent↗

IgA-driven T cell-mediated anti-bacterial immunity in man after live oral Ty 21a vaccine.

Cellular immunity against Salmonella typhi was observed by using a direct anti-bacterial in vitro assay in volunteers orally vaccinated with the live S. typhi mutant strain Ty 21a. With this experimental approach, it was demonstrated that Ty 21a vaccine also induces cellular immunity against S. paratyphi A and B. Interestingly, the mechanism involved in cellular immunity against bacteria seems to be of an antibody-dependent cellular cytotoxicity (ADCC) type, with IgA acting as the humoral arm and CD4+ T lymphocytes as the cellular one. In accordance with the increase in IgA-driven ADCC against S. typhi, a major rise in IgA against O and H antigens was observed in the serum of vaccinees in parallel to an increase in IgG of identical specificity. Furthermore, a Ty 21 vaccine induced cellular activity against flagellar antigens. These results indicate that IgA-ADCC by T lymphocytes against bacteria can originate from local stimulation of the gut mucosal immune system. This cellular defense mechanism might be at the origin of the protection induced by Ty 21a vaccine.

Administration, Oral↗