Search Results - (Author, Cooperation:E. Villa)

2016-02-27

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

2015-02-06

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Allosteric Regulation ; Binding Sites ; *Cryoelectron Microscopy ; DNA/chemistry/metabolism ; Enzyme Activation ; Mediator Complex/*chemistry/metabolism/*ultrastructure ; Models, Molecular ; Phosphorylation ; Protein Stability ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism ; RNA Polymerase II/*chemistry/metabolism/*ultrastructure ; Saccharomyces cerevisiae/*chemistry/*ultrastructure ; Saccharomyces cerevisiae Proteins/chemistry/metabolism/ultrastructure ; Transcription Factor TFIIB/chemistry/metabolism ; Transcription Factor TFIIH/chemistry/metabolism ; Transcription Initiation, Genetic

1089-7690

AIP Digital Archive

Physics

Chemistry and Pharmacology

The photodissociation and photodesorption dynamics of iodobenzene adsorbed at 150 K on LiF substrates has been investigated at 222 nm using the time-of-flight/resonance-enhanced multiphoton ionization/mass spectrometry technique. The Maxwell–Boltzmann (MB) translational temperatures (TB) calculated for the phenyl radical, atomic iodine in the I (2P3/2) and (2P1/2) states, and biphenyl were 1200, 1500, and 1050 K, respectively. The desorbed parent molecule (detected by electron ionization) was found to be translationally colder, with TB≈900 K. Analysis of translational energy distributions indicate that the adsorption–dissociation mechanism of iodobenzene differs significantly from that of the methyl halides.

Electronic Resource

1089-7690

AIP Digital Archive

Physics

Chemistry and Pharmacology

The aim of this work is to understand the molecular structural properties which may justify the great observed stability of doped alkoxy polythiophenes. Infrared frequency and intensity spectroscopy and Raman spectroscopy are used as probes. Suitably synthesized oligomers with increasing chain length and preassigned chemical structure have been studied together with several model molecules. The existence of through-space and through-bond S- - -O interactions has been revealed. The extent of the topologically dependent perturbation induced by the charge injection by the oxygen atoms is detected and measured. The inter- and intraring delocalizations have been monitored by the observation of the softening of the strongly Raman active "amplitude mode'' and by the red shift of the electronic spectra. The conformation of the side chains is trans planar in the solid state and collapses in a liquidlike premelting state before the melting of the crystal. © 1996 American Institute of Physics.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Combined medical treatment may provide further benefit to primary biliary cirrhosis (PBC) patients administered ursodeoxycholic acid (UDCA).〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To evaluate the long-term effects of colchicine and UDCA in symptomatic PBC patients.〈section xml:id="abs1-3"〉〈title type="main"〉Patients/methods:We extended up to 10 years the double-blind treatment of 44 symptomatic PBC patients originally included in a 3-year multicentre study comparing UDCA and colchicine (U + C) versus UDCA and placebo (U + P). Outcome measures were death or liver transplantation; incidence of clinically relevant events; clinical and quantitative variables retaining prognostic information.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Mean follow-up was 7 ± 3 years. One patient was lost, three withdrew because of jaundice (U + P); two patients stopped colchicine but remained on UDCA. Eleven patients (two for liver-unrelated reasons, U + P) and six patients (U + C) died, three and two patients, respectively, were transplanted (incidence rate difference, five cases per 100 patient-years; 95% CI, −1 to 11). Hepatocellular carcinoma developed in one (U + P) and four (U + C) patients (difference, −2; CI, −5 to 1), portal hypertension complications in nine patients from each group (difference, 1; CI, −5 to 6). Trends of serum bilirubin, Mayo score, antipyrine clearance were similar among treatment groups.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:In cirrhotic PBC patients, colchicine does not offer additional benefits to UDCA. In this population, UDCA does not obviate disease progression.

Electronic Resource

0009-2614

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Chemistry and Pharmacology

Physics

Electronic Resource

0009-2614

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Chemistry and Pharmacology

Physics

Electronic Resource

0009-2614

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Chemistry and Pharmacology

Physics

Electronic Resource

0009-2614

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Chemistry and Pharmacology

Physics

Electronic Resource

1365-3083

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Binding characteristics of a monovalenl bispecific monoclonal antibody (bsMoAb), which recognizes both epidermal growth factor receptor (EGF-R) and drug doxorubicin (DXR) were compared with those of the parental bivalent MoAb directed against the EGF-R binding site. Scatchard analysis indicated that both MoAbs bound to EGF-R-overexpressing A431 cells with the same affinity. In tracer amounts, both MoAbs also displayed the same capacity to be internalized after binding to the cell surface. However, when the MoAbs were used at saturating concentrations, down-modulation of the receptor was greater with the bivalent MoAb. The bivalent MoAb also inhibited proliferation of A431 cells both in vitro and in vivo whereas the bsMoAb was inhibitory only in vivo. These data suggest that MoAb bivalency is required for EGF-R down-modulation and in vitro cell growth inhibition.

Electronic Resource

1569-8041

carboplatin ; chemotherapy ; gemcitabine ; non-small-cell lung cancer ; paclitaxel

Springer Online Journal Archives 1860-2000

Medicine

Abstract Background:The combination of paclitaxel (P) and carboplatin (C)is an effective treatment for advanced NSCLC. Gemcitabine (G) is an active newdrug. We planned a phase I study to find the maximum tolerated dose (MTD) ofthe PCG combination. A phase II study was subsequently conducted to evaluatethe activity and toxicity of PCG. Patients and methods:Forty-five patients entered the study.Twenty-eight had stage IIIA–B disease, 17 stage IV. In the phase Istudy, with a fixed dose of C at AUC = 6 on day 1, P was escalated usingincrements of 25 mg/m2 starting from 175 mg/m2 on day1 and G with increments of 200 mg/m2 starting from 800mg/m2 on day 1 and 8. Results:Fourteen patients entered the phase I study. The MTD wasreached at P 200 mg/m2, C AUC = 6 and G 1000 mg/m2.Neutropenic fever and grade 3 diarrhea were the dose limiting toxicities.Thirty-one patients were treated in the phase II study with P 175mg/m2, C AUC = 6 and G 1000 mg/m2. Response rate was57% (68% in stage III and 47% in stage IV).Myelosuppression was the main toxicity, with grade 3–4 leukopeniaoccurring in 35% of cases. Grade 3 anemia was observed in 24%of cases and grade 3–4 thrombocytopenia occurred in 34% ofpatients. Non-hematological toxicity was mild. Median survival and one-yearactuarial survival were 20.5 months and 74% for stage III and 11.5months and 47% for stage IV. Conclusions:PCG is a promising regimen for treating advancedNSCLC. A phase III study comparing PCG to paclitaxel plus carboplatin inadvanced NSCLC is ongoing. On the other hand, we are planning to introduce thePCG regimen in the treatment of stage II–III patients in the setting ofa multimodality treatment.

Electronic Resource

1432-1440

Hepatitis C virus ; Genotypes ; Chronic active hepatitis ; Interferon

Springer Online Journal Archives 1860-2000

Medicine

Abstract The behavior of hepatitis C virus (HCV) infection with regards to type and number of HCV genotypes (tested with genotype-specific nested polymerase chain reaction) was evaluated in 60 patients with anti-HCV-positive chronic active hepatitis without cirrhosis [17 untreated and 43 subjects undergoing single or repeat courses of interferon (IFN) therapy] during a mean follow-up period of 76±18 months. In untreated patients (2 genotype I, 6 genotype II, 9 mixed infections) 4 out of 9 mixed infections selected for genotype II at the end of follow-up. Of the 43 treated patients 10 were long-term responders with histological remission, 6 were shortterm responders, and 22 did not respond. Fifteen of the latter patients received another course of IFN therapy, and only 3 patients responded. Eight of the 10 responders had infection with a single genotype (4 gt I, 3 gt II, 3 gt III). After IFN therapy, all but 2 patients cleared the HCV infection. The responders to the second IFN course (1 gt I, 1 gt II, 1 gt III) remained viremic. Of the shortterm responders, 2/6 patients had genotype II and 4 had a mixed infection (3 gt II±I and 1 gt II±III); gt III became prevalent in the latter in all but one patient. Of the nonresponders 18/24 had more than one genoytpe, 5 were genotype II at baseline and one had genotype I. At the end of the follow-up period 15/18 with mixed infection had selected for gt II (P〈0.01 vs. untreated patient). Thirteen of 18 nonresponders who selected genotype II during follow-up developed cirrhosis, compared with none among the four untreated which also selected for genotype II (P〈0.01) and with none of the patients maintaining their baseline genotype (P〈0.01). In conclusion, patients with single HCV genotype, other than gt II, respond better to IFN, which seems to easily suppress HCV genotypes other than II. Genotype II is scarcely inhibited and becomes predominant during follow-up. In the patients selecting for genotype II, cirrhosis develops more rapidly than in untreated patients, where the selection for genotype II occurs at much slower rate.

Electronic Resource

1432-0649

82.50 ; 82.65NZ

Springer Online Journal Archives 1860-2000

Physics

Abstract The photodesorption and photodecomposition pathways of dimethylgold hexafluoroacetylacetonate, DMG (hfac), adsorbed on a cooled quartz substrate is reported for 222-nm KrCl excimer laser radiation. The time-of-flight (TOF) of neutral photoproducts, desorbed from the surface of the gold film formed during the experiment, were analyzed under collisionless conditions by a differentially-pumped mass spectrometer. Extensive dissociation of adsorbed DMG (hfac) into DMG and the hfac ligand was observed. The ligand was found to recombine with a CH3 radical on the surface. Translational energy distributions for the detected species were obtained by deconvoluting the TOF curves into a self-consistent set of Maxwell-Boltzmann distributions for the desorbed parent molecule, laser-induced decomposition products, and surface recombination reaction products. The implications of these results for the mechanistic details of the low-pressure, laser-assisted organometallic deposition of DMG(hfac) are discussed.

Electronic Resource

1433-8580

Selective biliary obstruction (SBO) ; Bile acids ; Alkaline phosphatase ; Cytochrome-oxidase ; Glucose-6-phosphatase

Springer Online Journal Archives 1860-2000

Medicine

Summary Selective biliary obstruction (SBO) is a model of partial cholestasis in the rat in which the bile duct draining the median lobe is ligated and transected; the remaining biliary tree remains intact. Other authors introduced this experimental model and studied morphological and biochemical modifications in the liver after 2 days from surgery. They suggest that an adaptation may occur. Choosing some markers of cholestasis and some other markers of various cytoplasmic organelles, we studied the long-term effects that occur in serum and in total liver homogenate of selectively obstructed rats as compared to controls. Alkaline phosphatase activity and bile acids content, which were significantly higher than controls in serum and in total liver homogenate of the median lobe after 2 and 8 days from SBO, returned to normal range values after 30 days. Cytochrome-oxidase and glucose-6-phosphatase activity in total homogenate of the SBO median lobe remains perfectly similar to the control values in time. Results, together with morphological observations, suggest that cholestasis is present immediately after operation, then decreases gradually and disappears finally. The obstructed median lobe seems to cope with cholestasis.

Electronic Resource

1432-0843

Springer Online Journal Archives 1860-2000

Medicine

Summary The value of combination chemotherapy with HEXA-CAF was analyzed in 31 patients with histologically documented epithelial ovarian cancer in advanced stages (minimal or gross disease). No patient had been previously treated with chemotherapy. Peritoneoscopy with diaphragmatic inspection, peritoneal cytology, lymphography, and chest X-ray were routinely used in staging and restaging the patients. Complete (CR) plus partial (PR) responses were obtained in 13/31 fully restaged patients (41.9%). CR was recorded in seven patients (22.5%) and PR in six patients (19.3%). Remission duration was significantly longer in patients who achieved CR (20 months) than in those who attained PR (9.5 months)(P〈0.01). In all treated patients the median duration of survival was 16.5 months. Survival was significantly longer in patients with CR than in patients who did not achieve CR (P〈0.05). Nevertheless, considering the rate of CR in patients with gross disease (20.6%), HEXA-CAF combination seems a useful but not yet ahopeful treatment for patients with advanced ovarian carcinoma.

Electronic Resource

1432-119X

Springer Online Journal Archives 1860-2000

Biology

Medicine

Summary We have examined the ultrastructural characteristics of peroxidase activity in human bone marrow mast cells. These studies were performed in three patients with systemic mast cell disease, and in another six patients showing bone marrow mast cell hyperplasia. Endogenous peroxidase activity was localized in the perinuclear cisternae and strands of endoplasmic reticulum, but never in the granules. We have also demonstrated the “in vivo” existence of exogenous peroxidase activity in two of the three cases of systemic mast cell disease. The peroxidase internalization involved its binding to the plasma membrane, followed by its incorporation into the cell by a general endocytic process comprising the uptake of dispersed peroxidase-positive material mainly by phagocytosis of granular structures containing peroxidase. The exogenous peroxidase appeared in non-membrane bound granules, vacuoles or aggregates, but we have never seen the enzyme linked to the mast cell granules.

Electronic Resource

1569-8041

brain neoplasms ; chemotherapy ; combined treatment ; extranodal lymphomas ; primary central nervous system lymphoma ; radiotherapy

Springer Online Journal Archives 1860-2000

Medicine

Abstract Background: The optimal treatment for primary central nervous systemlymphomas (PCNSL) has not yet been defined. Patients and methods: Therapeutic results of 1180 immunocompetentpatients (pts) with PCNSL reported in 50 series published in English between1980 and 1995 were analysed. The impact on survival of age, treatmentstrategy, radiation field and doses, systemic and intrathecal chemotherapy(CHT) and treatment sequence was evaluated. Results: Univariate analyses showed a longer survival in pts of≤60 years (P 〈 0.00001); pts treated with 〉40 Gy to whole brain(WB) (P = 0.02); pts receiving 〉50 Gy to the tumor bed after a WBdose 〉40 Gy (P = 0.02); pts submitted to a combined treatment asopposed to CHT alone (P = 0.007) or radiotherapy alone (P 〈0.00001); pts receiving CHT followed by radiotherapy rather than in thereverse sequence (P = 0.05); pts treated with high-dose methotrexate(HD-MTX) (P = 0.04) and pts receiving intrathecal CHT (P = 0.03).Multivariate analysis confirmed the independent prognostic value of age, WBdose, HD-MTX and intrathecal CHT. Conclusions: Current data confirm the prognostic value of age andappear to support the use of systemic CHT consisting of HD-MTX and intrathecaldrug administration followed by 41–50 Gy to WB and 〉50 Gy to thetumor bed in the treatment of PCNSL in immunocompetent pts.

Electronic Resource

1569-8041

brain lymphomas ; chemotherapy ; intrathecal chemotherapy ; methotrexate ; primary central nervous system lymphoma ; radiotherapy

Springer Online Journal Archives 1860-2000

Medicine

Abstract Primary central nervous system lymphomas (PCNSL) are aggressivemalignancies, exhibiting one of the worst prognoses among lymphomas. The besttreatment modality for PCNSL has not yet been identified. Several therapeuticquestions still remain unanswered, and some methodological pitfalls inclinical trials prevent definitive conclusions from being drawn. In thisreview, certain aspects of trial design as well as emerging therapeuticguidelines are analyzed, and future perspectives are discussed. In the vast majority of prospective trials, general criteria for treatmentof aggressive lymphomas were adopted, choosing primary chemotherapy (CHT)followed by radiotherapy (RT) as therapeutic modality. This strategy produceda five-year survival of 22%–40% in comparison to the3%–26% reported with RT alone. Systemic high-dosemethotrexate (HD-MTX) seems to be the most effective drug, producing aresponse rate of 80%–90% and a two-year survival of60%–65%. To date, the addition of other drugs atconventional doses have not consistently improved outcome. With a fewexceptions, any regimen without HD-MTX comprehensively performed no betterthan RT alone. In combined treatment, RT doses should be decided on the bases of responseto primary CHT and the number of lesions, and, until definitive conclusionsfrom well-designed trials are available, RT parameters should follow thewidely accepted principles used for other aggressive lymphomas. CHT asexclusive treatment, keeping RT for relapses or persistent disease, appearsto be an attractive strategy. However, the worldwide experience with thismodality is still limited, and corroborating data are needed. Intrathecal CHTstill has not found a defined role in PCNSL management. Preliminary data seemto indicate that adequate meningeal treatment with HD-MTX, but withoutintrathecal CHT, could also be suitable in positive-cerebrospinal fluidpatients. Future efforts should be addressed to identify new active drugs and moreefficient CHT combinations, to evaluate the efficacy of high-dose CHTsupported by autologous peripheral blood stem cells transplantation, and toclarify the impact of RT delay in complete responders, the usefulness ofintrathecal CHT, and the best management for elderly patients. The assessmentof impact of treatment on neuropsychological functions and quality of life isa mandatory endpoint in clinical trials.

Electronic Resource

1615-6730

Key Words Idiopathic fecal incontinence ; Pudendal neuropathy ; Schlüsselwörter Idiopathische fäkale Inkontinenz ; Pudendusneuropathie

Springer Online Journal Archives 1860-2000

Medicine

Zusammenfassung Wir untersuchten die Langzeitergebnisse von Operationen, die wegen idiopathischer oder pudendaler neuropathischer (ohne Sphinkterverletzung) fäkaler Inkontinenz durchgeführt wurden. Elf Frauen, die sich einer partiellen oder totalen Muskelplikation des Beckenbodens unterziehen mussten, wurden postoperativ durch anorektale Inspektion, Manometrie, Elektromyographie und einen obstretrischen Fragebogen ausgewertet. Die Patientinnen dokumentierten die Schwere der fäkalen Inkontinenz mit Hilfe eines Defäkationstagebuches. In sechs Fällen wurde die Nachuntersuchung in der ambulanten Klinik durchgeführt (mit Wiederholung der präoperativen Tests), und in f¨nf Fällen durch telefonische Befragungen und das Defäkationstagebuch. Der prä- und postoperative Schweregrad der Inkontinenz wurde durch die Browning-Skala und ein Punktesystem bewertet, das in unserem Center entwickelt worden war. Wir fertigten eine beschreibende statistische Untersuchung an und bewerteten das postoperative Ergebnis, wobei die prozentualen Veränderungen mit den präoperativen Werten verglichen wurden. Das durchschnittliche Alter der Patientinnen betrug 61,2 Jahre mit einer Entwicklungszeit der fäkalen Inkontinenz von 5,5 Jahren. Der Grad der präoperativen Inkontinenz betrug gemäß Browning-Skala 63.6% in Gruppe D (n = 7, Inkontinenz für festen Stuhl) und 36,4% in Gruppe C (n = 4, Inkontinenz für flüssigen Stuhl). Die durchschnittliche Punktezahl entsprechend des in unserem Center entwickelten Systems lag bei 15,2/24 Punkten. Zwei posteriore Beckenbodenoperationen (18,2%) und neun doppelte Wiederherstellungen (81,8%) wurden durchgeführt. Das Ergebnis wurde in drei Fällen als ausgezeichnet eingestuft, in zwei Fällen als sehr gut, in vier als gut und als schlecht oder unverändert in zwei Fällen. Nach der Operation war bei den Patienten, die in unserem Center nachbetreut wurden (n = 6) der durchschnittliche Druck in Ruhe und beim Pressen niedriger als vor der Operation. Die Pudenduslatenz erschien postoperativ ebenfalls niedriger als vor der Operation (durchschnittliche Latenz 2,4 vs. 2,6 ms). Diese Verbesserung war bei den Patienten mit den besseren Ergebnissen (2,2 vs. 2,6 ms) deutlicher ausgeprägt, verglichen mit einer Latenzerhöhung bei den Patientinnen, bei denen die Operation keine Besserung zeigte (2,95 vs. 2,72 ms prä-bzw. postoperativ). Das Ergebnis einer operativen Behandlung wegen idiopathischer fäkaler Inkontinenz ist nicht so schlecht wie in der Literatur beschrieben. In diesem Zusammenhang gehen wir davon aus, dass die üblichen Operationstechniken als erste Behandlungsoption eher in Betracht gezogen werden sollten als neuere alternative Operationsmethoden.

Abstract A study is made of the long-term outcome of surgery for idiopathic or pudendal neuropathic (without sphincter damage) fecal incontinence. Eleven women subjected to partial or total muscle plication of the pelvic floor were postoperatively evaluated by anorectal inspection, manometry, electromyography and an obstetric questionnaire. The patients documented the severity of fecal incontinence by means of a defection diary. In 6 cases follow-up was carried out in the outpatient clinic (with repetition of the preoperative tests), and in 5 cases by means of telephone interviews and the defecation diary. The severity of incontinence before and after surgery was evaluated by the Browning scale and a score system developed in our center. A descriptive statistical study was made, and the postoperative outcome was rated in terms of the percentage changes with respect to the preoperative scores. Mean patient age was 61.2 years, with an evolution of fecal incontinence of 5.5 years. The degree of presurgical incontinence according to the Browning scale was 63.6% group D (n = 7 with incontinence to solids), and 36.4% group C (n = 4, incontinence to fluids). The mean score according to the system developed in our center was 15.2/24 points. Two posterior pelvic floor operations were carried out (18.2%), and 9 double repairs (81.8%). The outcome was considered excellent in 3 cases, very good in 2, good in 4 and poor or without change in 2. After surgery, and for the patients controlled in our center (n = 6), both the mean pressures at rest and upon straining were lower than before the operation. The pudendal latencies also appeared to decrease postoperatively vs. before surgery (mean latency 2.4 vs. 2.6 ms) – this improvement being apparent among the patients who improved (2.2 vs. 2.6 ms) compared with the increase in latency observed in those who failed to improve (2.95 v. 2.72 ms after and before surgery, respectively). The outcome of surgical management for idiopathic fecal incontinence is not as disappointing as has been reported in the literatur. In this context, we consider that the habitual surgical techniques should be regarded as a first treatment option over more recent alternative surgical procedures.

Electronic Resource

1573-7276

breast carcinoma ; laminin receptor ; monoclonal antibodies ; prognosis ; tumor marker

Springer Online Journal Archives 1860-2000

Medicine

Two monoclonal antibodies (mAbs), designated MLuC5 and MLuC6, were produced against a human small cell lung carcinoma cell line. They were found to exhibit a superimposable reactivity on different cell lines and on platelets. Moreover, they both immunoprecipitated a 67 kDa molecule from the membrane of the reference target cells. Immunodepletion and cross-inhibition tests indicated that the two mAbs recognize two epitopes closely localized on the same molecule. The MLuC5 mAb was further characterized for its reactivity on platelets. Immunoprecipitation and ELISA assays demonstrate that this mAb recognizes the 67 kDa high afinity laminin receptor. MLuC5 reactivity was evaluated by immunohistochemistry on a variety of normal and tumor tissues, in particular breast specimens including normal epithelium, dysplastic lesions, in situ carcinomas, invasive primary carcinomas and distant metastases. The laminin receptor was found to be strongly expressed in 50% of the infiltrating carcinomas, whereas in situ carcinomas and benign lesions, as well as the normal mammary epithelium, were only weakly and focally positive. In metastatic lesions MLuC5 reactivity was only found in 11% of the samples tested, independently of the site of origin of the lesion.

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