PubMed Health⌕ Search

Biomedical subjects

E Pagani

Publications and source records attributed to E Pagani.

34 records · Page 2Linked to original sources
PubMed1998

Mutation of the mismatch repair gene hMSH2 and hMSH6 in a human T-cell leukemia line tolerant to methylating agents.

Cell killing by monofunctional methylating agents is due mainly to the formation of adducts at the O6 position of guanine. These methyl adducts are removed from DNA by the O6-alkylguanine DNA alkyltransferase (OGAT). The mechanism by which O6-methylguanine (O6meG) induces cell death in OGAT-deficient cells requires a functional mismatch repair system (MRS). We have previously reported that depletion of OGAT activity in the human T-cell leukemic urkat line does not sensitize these cells to the cytotoxic and apoptotic effects of the methylating triazene temozolomide (Tentori et al., 1995). We therefore decided to establish whether the tolerance of Jurkat cells to O6meG could be associated with a defect in MRS. The results of mismatch repair complementation studies indicated that Jurkat cells are defective in hMutSalpha, a heterodimer of the hMSH2 and hMSH6 proteins. Cytogenetic analysis of two Jurkat clones revealed a deletion in the short arm of chromosome region 2p15-21, indicating an allelic loss of both hMSH2 and hMSH6 genes. DNA sequencing revealed that exon 13 of the second hMSH2 allele contains a base substitution at codon 711, which changes an arginine to a termination codon (CGA-->TGA). In addition, a (C)8-->(C)7 frameshift mutation in codon 1085-1087 of the hMSH6 gene was also found. Although both hMSH2 and hMSH6 transcripts could be detected in Jurkat clones, the respective polypeptides were absent. Taken together, these data indicate that tolerance of Jurkat cells to methylation damage is linked to a loss of functional hMutSalpha.

Base Pair Mismatch↗
PubMed1997

The value of a second injection on the pharmaco-induced erection test.

In order to test the capability of a reinjection to improve an incomplete pharmaco-induced erection, we submitted 30 impotent patients, with incomplete erectile responses to 10 micrograms PGE1 + 1 mg phentolamine, to a second injection of 15 micrograms PGE1 + 1.5 mg phentolamine + 30 mg papaverine, fifteen minutes after the first injection. Twenty-one patients improved their erection including nine who achieved complete rigidity. We conclude that incomplete pharmaco-induced erections can frequently be improved by reinjection.

Adrenergic alpha-Antagonists↗
PubMed1996

Clinical and hormonal aspects of male hypogonadism in myotonic dystrophy.

In order to study male hypergonadotropic hypogonadism as completely as possible, and to evaluate its possible effects on muscle atrophy and sexuality, RIA or IRMA methods were used to measure the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, total (T) and free (FT) testosterone, estradiol (E), dihydrotestosterone (DHT), sex hormone binding globulin (SHBG), androstenedione (A) and 17-OH-progesterone (17-OH-P) in 29 patients with myotonic dystrophy (MD). The mean hormonal levels +/-SD were: LH 8.0 +/- 4.4 mIU/ml, FSH 17.4 +/- 11.5 mIU/ml, A 200 +/- 130 ng/dl (all higher than in controls); T 406 +/- 290 ng/dl, FT 22.7 +/- 7.0 pg/ml, DHT 55.5 +/- 29.7 ng/ml (all lower than in controls). The low FT and DHT levels (never previously studied in MD) confirm the androgenic deficiency. The high androstenedione levels and low testosterone concentrations suggest defective enzyme 17-dehydrogenase. The duration of the disease correlated with both testosterone (r = -0.56) and FT levels (r = -0.59), showing that hypogonadism tends to worsen progressively. When the patients were divided into three groups on the basis of the severity of muscle involvement (A, B and C), LH and FSH levels were higher in group C (more severe disease) than in group A, respectively 9.3 +/- 4.7 and 20.6 +/- 12.3 mIU/ml versus 4.8 +/- 0.9 and 8.4 +/- 3.8, p < 0.03; T levels were lower in group C than in group A, 337.3 +/- 263.4 ng/dl versus 649.7 +/- 320.3 (p < 0.03); however, there was no significant difference in the FT levels of the three groups, which may imply that hypogonadism is unlikely to have a direct effect on muscle atrophy. About 25% of our patients were impotent; these subjects had higher LH and FSH (p < 0.001) and lower FT levels than the patients who were not impotent (p < 0.03). However, hypogonadism may not be the only cause of impotence as all of the impotent patients belonged to group C and had a very high (CTG)n triplet expansion. We hypothesise that hypogonadism and sexual impairment could be partially due to a muscle cell alteration: i.e. a dysfunction of both the testicular peritubular myoid cells and of the corpus cavernosum smooth muscle.

Adult↗
PubMed1995

The heme moiety of malaria pigment (beta-hematin) mediates the inhibition of nitric oxide and tumor necrosis factor-alpha production by lipopolysaccharide-stimulated macrophages.

To investigate the effect of the heme moiety of malaria pigment, hemozoin, on phagocyte functions, mouse macrophages were fed with insoluble beta-hematin, the synthetic heme-polymer chemically identical to the native pigment, or the soluble monomer, hematin. Production of inflammatory cytokines, interleukin 1 (IL1), tumor necrosis factor alpha (TNF alpha), and nitric oxide (NO) was assayed in the supernatants after stimulation with lipopolysaccharide. The results indicate that both beta-hematin and hematin induce a dose-dependent inhibition of macrophage production of TNF alpha and NO, but not of IL1. One-hour pretreatment with soluble hematin inhibited production of cytotoxic mediators by more than 50% compared to controls, while 6-hr exposure was necessary for insoluble beta-hematin to induce the same level of inhibition. However, the same treatment did not modify the production of TNF alpha and NO by mouse microglia cell lines. The inhibition was partially counterbalanced by adding sulphydryl group donors such as 2-mercaptoethanol, glutathione, or N-acetyl-cysteine during the preincubation time. The results of the present study confirm the inhibitory role of malaria pigment and show that such effect is due to the heme moiety and may be selective for the production of cytotoxic mediators by specific phagocytes. The implications of these findings in the control of malaria infection and disease and in the pathogenesis of severe malaria are discussed.

Animals↗
PubMed1995

Postzygotic instability of the myotonic dystrophy p[AGC] in repeat supported by larger expansions in muscle and reduced amplifications in sperm.

We have analysed the [AGC] expansion in leucocytes, muscle and sperm from 17 individuals affected by myotonic dystrophy (DM). Skeletal muscle showed a larger repeat number than leucocytes in the same patient. A similar degree of expansion was detected in differently affected muscles of a single patient. The germline mutation (< or = 350 repeats) was expanded in somatic cells of the progeny in all patients examined. Our results provide evidence of an early postzygotic instability of the [AGC] repeat in DM.

Adolescent↗
PubMed1995

Cardiac hemodynamic effects of iodixanol, iopamidol, and ioxaglate following left coronary injections in anesthetized dogs.

RATIONALE AND OBJECTIVES: Iodixanol, a dimeric, nonionic X-ray contrast medium, has been formulated at 320 mg iodine per milliliter and supplemented with Na+, Ca2+, and Cl- to produce an osmolality that approximates that of plasma. We compared the effects of left main coronary artery injections of iodixanol, ioxaglate, and iopamidol on cardiac mechanical function in dogs. METHODS: Six mixed-breed dogs were anesthetized and prepared for recordings for electrocardiogram, aortic and left ventricular pressures, and the first derivative of left ventricular pressure, dP/dt. The test solutions and saline were injected into the left coronary artery in a randomized order. The series of four injections were repeated three times in each animal for a total of 12 injections per dog. RESULTS: Iodixanol caused significantly lower (p < .05) reduction in peak left ventricular pressure (-1.7 +/- 0.9% vs -0.7 +/- 2.0%), in diastolic aortic pressure (-1.3 +/- 1.1% vs -9 +/- 1.3%), and in left ventricular dP/dt (0.3 +/- 1.3% vs -13.2 +/- 2.4%) than did ioxaglate. Iodixanol also produced smaller cardiovascular effects than did iopamidol, but the differences were not statistically significant. Injections of both iopamidol and ioxaglate caused significant decreases from baseline parameter values; however, the changes with iodixanol were not significant. CONCLUSION: The isotonic formulation of iodixanol caused smaller cardiovascular hemodynamic effects than did iopamidol and ioxaglate and may offer increased safety in patients with severe cardiac disease.

Animals↗
PubMed1994

Male hypogonadism in myotonic dystrophy is related to (CTG)n triplet mutation.

The Authors considered the relationship between hypogonadism in myotonic dystrophy (MD) and MT-PK gene mutation. Twenty-seven subjects were studied, and the (CTG)n amplification varied from 70 to 1520 (mean 661 +/- 463). Hypergonadotropic-hypogonadism with LH levels of 6.94 +/- 3.87 and FSH 14.54 +/- 9.58 IU/L was present; testosterone still showed normal values (505.7 +/- 376.2 ng/dl), but 44.4% of patients had abnormal serum level less than 250 ng/dl. We found a significant correlation (p < 0.001) between CTG repeat size and levels of both LH and FSH: these findings suggest that the severity of hypogonadism is related to MT-PK gene mutation.

Adult↗
PubMed1991

[The Pap test revisited].

The effectiveness of screening programmes based on cytological smears in reducing mortality from carcinoma of the cervix and the incidence of invasive disease is well established. But there is no evidence that the Papanicolau test has succeeded anywhere in complete eradication of this theoretically preventable disease. The major reason that many cervical cancer screening programmes have had little effect is that they fail to reach the women, particularly those aged over 40, who are most at risk of developing invasive carcinoma. Among women who are included in a programme, the principal failures are inadequate follow-up of abnormal smears, a long interval since the last smear, and false-negative smear results. Only when an acceptable participation level and follow-up system have been achieved should improvements in sensitivity assume. The potential failures of the system and the reasons for them and the remedies are described.

Female↗
PubMed1990

[Cervix uteri and human papillomavirus infections. Current approach].

The incidence of genital warts among sexually active young people is growing, but the association of human papillomavirus with abnormal cervical smears is not clear. The development of Cervical Intraepithelial Neoplasia (CIN) may be expected within one year by one third of patients with histologically documented viral cytopathic effects. The presence of HPV infection in colposcopically normal cervical tissue both inside and outside the transformation zone may help to explain why current methods for treatment of cervical HPV infection are often unsuccessful. A significant proportion of the male population is infected in countries were HPV is an important factor in cervical carcinogenesis. Patients may be considered cured when cytology and colposcopy are found to be negative in two subsequent examinations. At the moment we simply do not know whether or not HPV causes cervical cancer. Perhaps shortly we will be able to write with greater certainty.

Condylomata Acuminata↗
PubMed1989

The role of thiols in lethal and mutational radiation damage.

Over the last few decades, free radicals have been increasingly implicated in biological processes including radiation effects, ageing, carcinogenesis, initiation and progression of various diseases, toxicity of chemicals and drugs. In this field Radiation Biology has played an important role in the development of both technical and cultural background, because it was very soon recognized the radical nature of processes following exposure to ionizing radiation. Several studies have pointed out the importance of both radicals, reacting with cellular targets, and endogenous thiols, mainly represented by glutathione, in controlling radiation responses of living cells. Experimental supports for such a role mainly rest on observations made on cell lines depleted of glutathione content because of a genetic defect or as result of a pharmacological manipulation. We present a study on the influence of endogenous and exogenous thiols on the correlation between lethal and mutational damage in mammalian cells. Survival (S) and induction of HPRT- mutation (M) were measured in cells irradiated with X-rays either after treatment with BSO or in the presence of MEA or GSH. In control experiments log of S is linearly correlated to M. Incubation with 1 mM BSO reduces cellular GSH content and produces an increase in radiosensitivity with regard to both lethal and mutagenic effects. In the presence of MEA a concentration dependent radioprotective effect can be observed on both end-points. GSH added to cells immediately or 90 min before irradiation only displays a slight protective effect on lethality. The yield of mutant cells is not significantly affected when GSH is added immediately before irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

[Para-albuminemia and alloalbuminemia: 1st case report of a VR/VR B genetic variant in the Novara area].

The 12th case of alloalbuminaemia in Piedmont, and the 1st in the Novara area, coded NO/PN, are reported. Although alloalbuminaemia is at present purely a clinically asymptomatic scientific curiosity, future investigations could link it to other genetic marks with consequent practical advantages. It is also important to distinguish this form from acquired para-albuminaemia, often the only sign of pancreatic fistulisation.

Albumins↗
PubMed1976

[Determination of CPK isoenzymes by column chromatography (author's transl)].

The AA. have carried out in patients affected by proved myocardial infarct, by other cardiac diseases and by muscular dystrophy the following enzymes determinations: total CPK, total LDH, SGOT, SGPT, HBDH, CPK isoenzymes by column chromatography (Mercer's method) and LDH isoenzymes either by column chromatography (Mercer's method) and by electrophoretic separation. Some results concerning the appearance of the CK-MB isoenzymes during the acute period of the myocardial infarction are described.

Adult↗
PubMed1976

[Platelets aggregation employing ADP and cephalin. Comparative tests (author's transl)].

The AA. have carried out researches into the results of the platelets aggregation test (PAT) on 375 people by use of the Born method; they have employed ADP and a commercial available cephalin (Thrombofax, Ortho). In the first case the parameters taken into consideration are: the minimum dose of ADP able to cause a "double wave aggregation", the slope and the maximum increase in light transmission; in the second case the parameters considered are: the latency period, the maximum speed and the maximum amplitude. The normal values, in 75 persons, are: --6 +/- 2 X 10(-7)M (min dose wor "double wave"); --15,5 +/- 4,9 UT/min (slope); -- 46,3 +/- 6,8 UT (max increase in light transmission); regarding ADP aggregation. --90 +/- 40 sec (latency period); -- 30 +/- 15 UT/min (max speed); -- 52 +/- 4,63 UT (max amplitude); relating to Thrombofax aggregation. Analyses of PAT, by parallel using both aggregating agents, have been made on 260 women undergoina an oestrogen-progestative therapy, on 25 daibetic subjects and on 15 subjects undergoing an anti-aggregation oral therapy (Ageroplas, Serono, Roma). The AA. stress on the validity of ADP as an aggregation agent in routine tests, while Trombofax has revealed itself to be not very sensitive in all the cases with hyperaggregation. However it is to be noted that use of cephalin results interesting in tests made on subjects undergoing an anti-aggregation therapy, as the PAT parameters seen proportional to the quantity of the drug given to the patient, which is just the opposite of what happens with ADP.

Adenosine Diphosphate↗