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Biomedical subjects

A Cerri

Publications and source records attributed to A Cerri.

At least 91 records · Page 5Linked to original sources

Production of chi(c1) and chi(c2) in pp collisions at sqrt[S] = 1.8 TeV.

We have measured the ratio of prompt production rates of the charmonium states chi(c1) and chi(c2) in 110 pb(-1) of pp collisions at sqrt[s] = 1.8 TeV. The photon from their decay into J/psi(gamma) is reconstructed through conversion into e+e- pairs. The energy resolution this technique provides makes the resolution of the two states possible. We find the ratio of production cross sections sigma(chi(c2))/sigma(chi(c1)) = 0.96+/-0.27(stat)+/-0.11(syst) for events with pT(J/psi) > 4.0 GeV/c, /eta(J/psi)/ < 0.6, and pT(gamma) > 1.0 GeV/c.

Journal Article↗

First measurement of the ratio B(t --> Wb)/B(t --> Wq) and associated limit on the Cabibbo-Kobayashi-Maskawa element /V(tb)/.

We present the first measurement of the ratio of branching fractions R identical withB(t-->Wb)/B(t-->Wq) from p_p collisions at sqrt[s] = 1.8 TeV. The data set corresponds to 109 pb(-1) of data recorded by the Collider Detector at Fermilab during the 1992-95 Tevatron run. We measure R = 0.94(+0.31)(-0.24)(stat+syst) or R>0.61 (0.56) at 90% (95)% C.L., in agreement with the standard model predictions. This measurement yields a limit on the Cabibbo-Kobayashi-Maskawa quark mixing matrix element /V(tb)/ under the assumption of three generations and unitarity.

Journal Article↗

High sensitivity of human epidermal keratinocytes (HaCaT) to topoisomerase inhibitors.

In the panorama of the numerous established cell lines, the human keratinocyte line HaCaT has a very interesting feature, having a close similarity in functional competence to normal keratinocytes. This cell line has been used in many studies as a paradigm for epidermal cells and therefore we selected HaCaT as a cell model for investigating the activity of three antitopoisomerase drugs (Camptothecin, Doxorubicin, Ciprofloxacin) on in vitro cell growth. The effect was evaluated both by a 24-h cytotoxicity test and by a 7-day antiproliferation assay, in which the cell viability was assessed by an MTT (3-(4,5-dimethyl-2-thiazolyl) 2,5-diphenil-2-H-tetrazolium bromide) test. DNA topoisomerase I was also partially purified from a nuclear extract of HaCaT cells, the level of topo I catalytic activity was measured by a pBR322 DNA relaxation assay and then the in vitro effect of antitopoisomerase drugs on the target enzyme was also assessed. The results indicated that the in vitro sensitivity of human epidermal HaCaT cells to antitopoisomerase drugs is comparable to that of many human tumour cell lines. HaCaT cells express a high level of topoisomerase I activity that is significantly inhibited by both Camptothecin and Doxorubicin and to a minor degree by Ciprofloxacin. A high correlation between the cell sensitivity to the antitopoisomerase I drug measured by the MTT test and the in vitro direct inhibition of HaCaT topoisomerase I was observed, suggesting that HaCaT cells can represent a very interesting model both for studying cellular pharmacokinetics of antineoplastic drugs on keratinocytes and for predicting possible secondary effects, exerted by these drugs on cutaneous cells, during treatment with chemotherapy.

Anti-Bacterial Agents↗

Usefulness of histological examination for the diagnosis of onychomycosis.

BACKGROUND: [corrected] Direct microscopy and culture tests currently used in the diagnosis of nail mycosis can yield false-negative results, and confirmation of the pathogenic agent, especially in non-dermatophyte infections, is often a lengthy process. OBJECTIVE: The aim of this study was to investigate the usefulness of the histological examination of nail clipping samples in supplementing the standard microscopic and culture techniques for the diagnosis of onychomycosis. PATIENTS AND METHODS: One hundred and seventy-two subjects affected by nail alterations suggestive of onychomycosis were evaluated. Nail specimens were studied with 3 different techniques: direct microscopic examination of a 40% KOH clarified preparation, fungal culture and histological examination. Patients positive for fungal infection were re-evaluated with the same techniques after treatment with oral terbinafine, fluconazole or itraconazole and topical application of bifonazole or ciclopirox for 2 months. RESULTS: Direct microscopy was positive in 102 (59.3%) nail specimens. The culture test was positive in 90 cases (52.9%), showing a dermatophyte in 45, a yeast in 23 and a mould in 22 samples. The histological examination was positive in 94 (54.6%) samples. In 4 cases, it was the only investigation confirming the clinical diagnosis of nail mycosis. In most of the cases, the morphological aspect of the hyphae and/or spores suggested also to which group of pathogens (dermatophytes, yeasts or moulds) the mycetes observed in the histological sections could be ascribed. The concurrent presence of a dermatophyte and a mould was evidenced in a few specimens. The control histological examination at the end of the treatment showed negative results or residual non-vital hyphae and/or spores. CONCLUSIONS: Results of the present study indicate that the histological examination of nail clipping specimens is a relatively inexpensive, rapid and easily performed procedure. It is useful to confirm or refute the results of routine microscopy and culture tests. Moreover, nail histopathological observation may help in ascribing a pathogenic role of non-dermatophyte isolates and evaluating the effectiveness of antifungal treatment.

Adolescent↗

Seborrheic keratosis with compound nevus, junctional nevus and basal cell carcinoma in the same lesion.

Seborrheic keratosis can be associated with different neoplasms such as basal cell carcinomas, squamous cell carcinomas and melanomas. We describe an unusual case of a man who presented with a brown plaque on his back. The clinical diagnosis was melanoma. Histopathologic examination of the lesion revealed four neoplasms: a compound nevus, a junctional nevus, a superficial basal cell carcinoma and a seborrheic keratosis. Although this association most likely represents a chance phenomenon, we discuss the possibility that the seborrheic keratosis developed from the nevus, and that subsequently the junctional nevus and the basal cell carcinoma developed from the seborrheic keratosis.

Back↗

Genetic determinants of alcohol addiction and metabolism: a survey in Italy.

BACKGROUND: Although multiple genes are involved in alcoholism and can contribute differently to the risk of dependence and liver damage, no studies have investigated susceptibility to addiction in combination with susceptibility to liver damage due to differences in ethanol metabolism. METHODS: We evaluated the role of three polymorphic genes related to alcohol metabolism (CYP2E1) and, possibly, dependence (DRD2 and SLC6A4 promoter) in a series of 60 alcoholics admitted to a specialized referral center in Florence, Italy. Eighteen had a diagnosis of liver cirrhosis. A control series of 64 blood donors were identified at the same hospital. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: No difference was found in the frequency of the CYP2E1 Rsal c2 allele (2.5% among alcoholics and 4.7% among controls) and the DraI C allele (6.7% and 10.1%). Similarly, no difference was found in the frequency of the DRD2 A1 allele (15.8% and 13.3%) and the B1 allele (10.8% and 8.6%). The proportion of controls with a combined B1 genotype (B1/B1 or B1/B2) was significantly associated with smoking (p = 0.03). The distribution of the S and L allele of the SLC6A4 gene was similar in the two groups, with 15% and 14%, respectively, homozygous S/S carriers. A significant association, however, emerged in the group of alcoholics, with a five times higher risk for S/S carriers of developing cirrhosis (p < 0.05). This association with liver persisted even after exclusion of the subgrouped of 10 hepatitis C virus positive alcoholics. CONCLUSIONS: Overall, our results provided no evidence of an increased susceptibility to develop alcoholism that was associated with the three genotypes investigated, either alone or in combination. An increased risk of developing liver cirrhosis for S/S homozygous carriers among alcohol-dependent patients was observed for the first time.

Adult↗

Measurement of J/psi and psi(2S) polarization in pp collisions at sqrt[s] = 1.8 TeV.

We have measured the polarization of J/psi and psi(2S) mesons produced in pp collisions at sqrt[s] = 1.8 TeV, using data collected at the Collider Detector at Fermilab during 1992-1995. The polarization of promptly produced J/psi [psi(2S)] mesons is isolated from those produced in B-hadron decay, and measured over the kinematic range 4 [5.5]<P(T)<20 GeV/c and |y|<0.6. For P(T) greater than or approximately equal 12 GeV/c we do not observe significant polarization in the prompt component.

Journal Article↗

Search for scalar top and scalar bottom quarks in pp collisions at square root s=1.8 TeV.

We have searched for direct pair production of scalar top and scalar bottom quarks in 88 pb-1 of pp collisions at sqrt[s]=1.8 TeV with the CDF detector. We looked for events with a pair of heavy flavor jets and missing energy, consistent with scalar top (bottom) quark decays to a charm (bottom) quark and a neutralino. The numbers of events that pass our selections show no significant deviation from standard model expectations. We compare our results to the next-to-leading order scalar quark production cross sections to exclude regions in scalar quark-neutralino mass parameter space.

Journal Article↗

Search for a W' boson via the decay mode W'-->munumu in 1.8 TeV pp collisions.

We report the results of a search for a W' boson produced in pp collisions at a center-of-mass energy of 1.8 TeV using a 107 pb-1 data sample recorded by the Collider Detector at Fermilab. We consider the decay channel W'-->&munumu and search for anomalous production of high transverse mass munumu lepton pairs. We observe no excess of events above background and set limits on the rate of W' boson production and decay relative to standard model W boson production and decay using a fit of the transverse mass distribution observed. If we assume standard model strength couplings of the W' boson to quark and lepton pairs, we exclude a W' boson with invariant mass less than 660 GeV/c2 at 95% confidence level.

Journal Article↗

17beta-O-Aminoalkyloximes of 5beta-androstane-3beta,14beta-diol with digitalis-like activity: synthesis, cardiotonic activity, structure-activity relationships, and molecular modeling of the Na(+),K(+)-ATPase receptor.

A series of digitalis-like compounds with a 17-aminoalkoxyiminoalkyl or -alkenyl substituent was synthesized and evaluated for inhibition of Na(+),K(+)-ATPase and for inotropic activity. The highest inhibition was found with compounds having the substituent in configuration 17beta and the amino group at a distance of 6 or 7 bonds from C(17) of the digitoxigenin skeleton. The presence of the oxime function strengthens the interaction with the receptor, more if alpha,beta-unsaturated, thus mimicking the electronic situation of the unsaturated lactone in natural digitalis compounds. The most active compounds showed Na(+),K(+)-ATPase inhibitory potencies (IC(50)) 17-25 times higher than the standards digitoxigenin and digoxin and 3-11 times higher inotropic potencies (EC(50)) in isolated guinea pig left atria. These features are supported by a molecular model suggesting the possible interactions of the groups described above with particular amino acid residues in the H1-H2 domains of Na(+),K(+)-ATPase. Some interactions are the classical ones already described in the literature; a new, very strong interaction of the basic group with the Cys138 was found and adds new possibilities to design compounds interacting with this region of the receptor. The most interesting compounds were also studied in vivo in the anesthetized guinea pig for evaluating their inotropic effect versus the lethal dose. Compounds 9 and 12 showed a slightly higher safety ratio than digoxin and deserve further evaluation.

Androstanes↗

Non-dermatophytic onychomycosis. An understimated entity? A study of 51 cases.

The aim of our study was to evaluate the incidence, the clinic characteristics, the therapeutic antifungal response and the evaluation of side-effects in 51 non-dermatophytic onychomycosis cases which were observed in a case-study of 1012 patients, affected by different types of onychopathy, attending the Mycology Ambulatory of San Paolo Hospital, Milan, Italy during the period 1994-97.

Antifungal Agents↗

Replacement of the quinoline system in 2-phenyl-4-quinolinecarboxamide NK-3 receptor antagonists.

Results from a medicinal chemistry approach aimed at replacing the quinoline ring system in the potent and selective human neurokinin-3 (hNK-3) receptor antagonists 1-4 of general formula I are discussed. The data give further insight upon the potential NK-3 pharmacophore. In particular, it is highlighted that both the benzene-condensed ring and the quinoline nitrogen are crucial determinants for optimal binding affinity to the hNK-3 receptor. Some novel compounds maintained part of the binding affinity to the receptor (5, 6, 10 and 13) and compound 5, featuring the naphthalene ring system, appears to be suitable for further modifications; it offers the option to introduce electron-withdrawing groups at position 2 and 4, conferring on the ring an overall electron-deficiency similar to that of the quinoline.

Animals↗

A new approach to the design of novel inhibitors of Na+,K+-ATPase: 17alpha-substituted seco-D 5beta-androstane as cassaine analogues.

A new three-dimensional model for the relative binding mode of cassaine 1 and digitoxigenin 2 at the digitalis receptor site is proposed on the basis of the structural and conformational similarities among 1, 2 and its 14,15-seco analogues 3 and 4. Accordingly, the speculation that also 17alpha-substituted derivatives of the digitalis 5beta,14beta-androstane skeleton could efficiently bind to the Na+,K+-ATPase receptor is put forward and verified through the synthesis of some related compounds. The binding affinity shown by 2-(N,N-dimethylamino)ethyl 3beta, 14-dihydroxy-5beta,14beta-androstane-17alpha-acrylate 6 (IC50 = 5.89 microM) and, much more significantly, by the corresponding 14, 15-seco-14-oxo derivative 9 (IC50 = 0.12 microM) substantiates the new hypothesis and opens new prospects to the design of novel inhibitors of Na+,K+-ATPase as potential positive inotropic compounds.

Abietanes↗

Previous diathermic therapy at the site of the development of basal cell carcinomas. A hypothesis of association.

BACKGROUND: Factors associated with the development of basal cell carcinomas (BCCs) are radiation exposure, sunlight, trauma, and burns. OBJECTIVE: We wish to further document the relationship between the development of BCCs and previous diathermic exposure for therapeutical purposes. Moreover, we compared the histological subtypes of BCCs developed in patients with or without previous therapy. METHODS: A retrospective study of 1053 patients with BCCs seen at our dermatologic clinic was performed. RESULTS: Twenty-three patients had histories of diathermic therapy for different osteoarticular problems. The interval of time between the treatments and the appearance of the tumor was 12-31 years. The histologic subtypes involved were the same of other BCCs on the same areas. CONCLUSIONS: Our study supports the association of BCCs and diathermic therapy in the development of the tumor of the previously treated areas. Histological subtypes do not seem to be affected by environmental factors but are a characteristic of the site location of the tumor.

Basal Cell Carcinoma↗

Impact of inherited polymorphisms in glutathione S-transferase M1, microsomal epoxide hydrolase, cytochrome P450 enzymes on DNA, and blood protein adducts of benzo(a)pyrene-diolepoxide.

The benzo(a)pyrene (BaP) metabolite benzo(a)pyrenediolepoxide (BPDE) is strongly implicated as a causative agent of lung cancer. To assess the risk of exposure to BaP, we made a combined analysis of levels of BPDE adducts to hemoglobin (Hb), serum albumin (SA), and lymphocyte DNA in 44 patients with incident lung cancer, as a prototype of a population mainly exposed to tobacco-derived BaP. We also investigated whether genetic polymorphisms of cytochrome P450IA1 (CYPIA1), microsomal epoxide hydrolase (mEH), and glutathione S-transferase M1 (GSTM1), which are involved in BaP metabolism, can be determinants of adduct formation. BPDE-Hb, BPDE-SA, and BPDE-DNA adducts were quantified as BaP tetrols released from hydrolysis of macromolecules and measured by high-resolution gas chromatography-negative ion chemical ionization-mass spectrometry to achieve high specificity and sensitivity. Individuals with detectable Hb adducts were positive for SA adducts but not vice versa, suggesting that BPDE-Hb adducts are less informative indicators of BaP exposure. Using PCR methods on DNA, we characterized GSTM1 deletion, CYPIA1 MspI and exon 7 valine variants, and mEH polymorphisms at amino acid positions 113 (EH3) and 139 (EH4). Levels of BPDE adducts were no different among CYPIA1, mEH, and GSTM1 genotypes. However, individuals with measurable BPDE-SA adducts were CYPIA1 variant carriers more frequently (P = 0.03). There was a slightly higher percentage of DNA detectable adducts in subjects with CYPIA1 exon 7 valine polymorphism. When subjects were classified by both polymorphisms on the mEH gene, those with two slow alleles (EH3 homozygous mutated) and no fast alleles (EH4 homozygous wild type) had a lower frequency of BPDE-SA adducts and no DNA adducts (P = 0.06). These results are based on a small number of observations thus far, but this exploratory study suggests that CYPIA1 and mEH variants might have an impact on BPDE exposure markers such as BPDE-SA adducts. Chemical specificity in adduct measurements is important to identify the biomarkers that reflect BaP exposure more accurately.

Aged↗