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At least 1,747 records · Page 97Linked to original sources
PubMed1998

Multimode interaction of Hoechst 33258 with eukaryotic DNA; quantitative analysis of the DNA conformational changes.

The interaction of the minor groove binding ligand Hoechst 33258 (Hoe) with natural DNA was investigated by high resolution titration rotational viscometry. Analysis of the concomitant DNA conformational changes was performed with two DNA samples of sufficiently different molar mass M, at 4 degrees C, 22 degrees C and 40 degrees C, for Hoe/DNA-P ratios below r = 0.02. In this narrow r range several interaction modes could be resolved. The measured conformational changes were quantified in terms of relative changes of both apparent DNA persistence length, delta a/a, and hydrodynamically operative DNA contour length, deltaL/L. Delta a/a(r) primarily is a measure of ligand-induced DNA helix stiffening, but both, delta a/a(r) and deltaL/L(r), generally depend also on ligand binding induced DNA bending or DNA unbending. The essential difference obviously is that delta a/a(r) is influenced by the randomly distributed helix bends and deltaL/L(r) by phased ones. The measurements performed at different temperatures deliver informations about existence and temperature dependent abolition of intrinsic helix curvature. Both Hoe and netropsin (Nt) prefer binding to AT rich DNA segments, which are candidates for intrinsic DNA helix bends. But our data for Hoe interaction with calf thymus DNA (ctDNA) show characteristic differences to those for Nt-ctDNA interaction. Especially for Hoe, the mode of highest affinity is saturated already at a ligand concentration of roughly 1 nM (r approximately = 0.0015 Hoe/DNA-P). It exhibits an unusually strong temperature dependence of the conformational DNA response. A Hoe-Nt competition experiment shows that Hoe binding to the sites of the very first Hoe mode is almost unaffected by bound Nt. But Hoe binding to the sites of the following Hoe modes does not occur due to the competition with Nt. Thus this mode of strongest Hoe-DNA interaction reflects a unique mechanism, possibly of high relevance for gene regulatory systems.

Animals↗
PubMed1999

DNA multimode interaction with berenil and pentamidine; double helix stiffening, unbending and bending.

The antitrypanosomal drugs berenil (Ber) and pentamidine (Pm) preferentially bind to DNA in the minor groove of A.T-rich domains. The properties of A.T clusters are essential for sequence-mediated helix bending. Groove binding drugs locally stiffen the DNA helix but may also change intrinsic helix bends or may bend straight DNA. Ligand binding to randomly distributed sites alters the apparent DNA persistence length, a. Criteria permit the distinction of the underlying mechanism(s). Helix bends, if phased with the helix screw, however, generate solenoidal superhelix components mediating an apparent change of the hydrodynamically effective DNA contour length, L. The measurement of relative changes of both, a and L, as induced by Ber or Pm is performed by titration rotational viscometry. The determination of the two quantities requires two independent measurements: the relative change of DNA intrinsic viscosity, deltay, for short (tending to rod-like) DNA molecules and for comparably long (almost coil-like) ones as a function of r, the bound drug molecules per DNA-P, and this under conditions effectively excluding intramolecular DNA-DNA crosslinking effects. At least at r< or =0.05 and < or =0.03, respectively, the two drugs virtually bind completely to a eukaryotic DNA. r ranges of different drug binding strength and, concomitantly, of different specific conformational response, could be resolved. They represent (sub)modes of different DNA sequences... Whereas the mode-specific elongation effects are fairly similar for both systems, there are pronounced quantitative differences in the relative change of DNA persistence length. The sites of highest Ber-binding strength are correlated to unbent alternating helical A.T segments followed by bent and by less bent or unbent dAn.dTn tracts straightened on Ber-binding. For Pm-DNA interaction the ligand bends the sites of highest Pm affinity. Generally, ligand induced and sequence mediated local DNA-bend removal or DNA bending, as observed for several modes of interaction with A.T rich DNA, are considered to be of gene regulatory relevance.

Animals↗
PubMedDate not supplied

Multimodal neuroimaging studies and neurodevelopment and neurodegeneration hypotheses of schizophrenia.

The interpretation of the huge number of results in schizophrenia research using neuroimaging is uncertain. However, the simultaneous use of complimentary data obtained with these techniques may yield more relevant information in this regard. In this paper we present a series of studies performed by our group in two schizophrenic samples with the use of structural (magnetic resonance imaging, MRI), functional [glucose positron emission tomography (PET) and N-acetyl-aspartate (NAA) magnetic resonance spectrocopy] and neurophysiological techniques (the P300 event-related potential). Transversal and longitudinal measurements were performed.The integrated vision of the results so obtained allows us to propose the hypothesis of a neurodevelopmentally determined state of prefrontal disinihibition, in which the degree of atrophy would directly relate to the metabolic rate. This state would already be present in the first stages of illness and could have neurotoxic consequences in the long term. This would explain the findings of an association between sulcal cerebrospinal fluid (CSF) and illness duration and decreased NAA levels in chronic but not in recent-onset cases. The prefrotnal disinhibition would overstimulate the limbic system and the hippocampus would become overactivated, the metabolic rate at this level being inversely related to P300 amplitude. Clozapine showed a more selective and intense action on that hyperactive metabolic tone than haloperidol.

Journal Article↗
PubMedDate not supplied

Multimodal use of computed tomography in early acute stroke, part 1.

Brain Computed tomography (CT) scan has been used in the past to exclude a hemorrhagic stroke, to determine a possible cause of the stroke patient symptoms, and to demonstrate a stabilized area of hypoperfusional flow. Several results from CT scan studies suggested that we could have new information on prognosis and outcome, localization, and risk of infarction. In this view, CT scan in acute stroke may contribute, using objective measures, to evaluate the inclusion in clinical and therapeutical trials, such as thrombolytic therapy. The lack of consensus among clinicians does not allow a secure and definitive system of CT scan evaluation. Besides its common uses, more recently brain CT scan provides new techniques utilizing advanced algorithms of reconstruction, with promising properties not yet completely verified, to highlight more aspects of acute stroke in the early phase. Despite this limitation, progress on neuroradiological techniques reinforces the concept that brain CT scan remains the key of studies, as well as of validation and routine treatment in terms of feasibility, low cost, and widely availability.

Acute Disease↗
PubMed1990

Multimodal biochemical modulation of 5-fluorouracil activity in advanced colorectal cancer with allopurinol, folinic acid and dipyridamol.

It is now commonly accepted that the activity of 5-fluorouracil (5FU) may be potentiated by folinic acid (FA). Moreover dipyridamol (DIP) interacts with the pyrimidine salvage pathway of 5FU. In 28 patients with advanced colorectal cancer, in progression under FA-5FU, we continued treatment with FA-5FU plus DIP. FA 200 mg/m2/day. i.v. push was given before 5FU 766.52 mg/m2/day (mean dose), in 60 min infusion for 5 subsequent days. Cycle was repeated every 21 days. We noticed greater but not seriously increased toxicity by the addition of DIP. The addition of DIP did not change response rates; it seemed to increase response but not significantly.

Allopurinol↗
PubMed2005

Multimodality imaging of borderline left main coronary disease using fluoroscopy, IVUS and CT coronary angiography.

A borderline left main narrowing was discovered during coronary angiography in a young asymptomatic man with positive stress test. IVUS demonstrated minimal diameter of 2.9 mm and the cross-sectional area was 11.5 mm(2). CTs were performed, and an eccentric calcific plaque was imaged at the ostium of the left main. Based on all three image modalities after discussing the different therapeutic options with the patient he was referred for bypass surgery.

Coronary Angiography↗
PubMed1990

Patch-clamp measurements reveal multimodal distribution of granule sizes in rat mast cells.

Using patch-clamp techniques, we have followed the attributes of the secretory granules of peritoneal mast cells obtained from rats of different ages. The granule attributes were determined by following the step increases in the cell surface membrane area caused by the exocytosis of the granules in GTP gamma S stimulated mast cells. Our data show that the amount of granule membrane available for exocytosis depends exponentially on the weight (age) of the donor rat, reaching a maximum at approximately 300 g. The data are consistent with an exponential growth in the number of granules contained by mast cells of maturing animals. Histograms of the sizes of the step increases in surface area caused by exocytosis of the granules showed at least four equally spaced peaks of similar variance where the position of the first peak and the spacing between peaks averaged 1.3 +/- 0.4 micron2. In all cells recorded, no more than seven peaks could be found, the higher order peaks having a lower probability of occurrence. The distribution of granule sizes did not change measurably between young and adult animals. This study suggests that at least two separate steps may determine the size of a secretory granule: granule to granule fusion that may account for the subunit composition of granule sizes and traffic of microvesicles through the maturing granules that may account for the variance observed in the granule sizes. This study also demonstrates a novel way to study granulo-genesis in living cells.

Aging↗
PubMed2000

The Detection of Multimodal Oscillations on alpha Ursae Majoris.

We have used the star camera on the Wide-Field Infrared Explorer satellite to observe the K0 III star alpha UMa, and we report the apparent detection of 10 oscillation modes. The lowest frequency mode is at 1.82 µHz, and it appears to be the fundamental mode. The mean spacing between the mode frequencies is 2.94 µHz, which implies that all detected modes are radial. The mode frequencies are consistent with the physical parameters of a K0 III star, if we assume that only radial modes are excited. Mode amplitudes are 100-400 µmag, which is consistent with the scaling relation of Kjeldsen & Bedding.

Journal Article↗
PubMed1994

Multimodality treatment of locally advanced pancreatic cancer.

BACKGROUND: The prognosis of locally advanced pancreatic cancer is poor (median survival 3-5 months). In view of the localized character of this disease several groups have explored the value of combined modality treatment. The conditions are that a good local treatment and an effective systemic treatment are available. PATIENTS AND METHODS: The results of irradiation and of chemotherapy in advanced disease are reviewed. RESULTS: An overview of combined modality treatment has been given. CONCLUSIONS: Results of combined modality treatment are superior to irradiation alone or to symptomatic treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Long-term survival in an adult metastatic renal peripheral primitive neuroectodermal tumor (PPNET) with multimodality treatment including high-dose chemotherapy.

We describe a 42-year-old male patient with a primitive peripheral neuroectodermal tumor (PPNET) arising from the kidney. The patient was treated sequentially with surgery, radiotherapy, experimental cytokine treatment (rhIL-6), combination chemotherapy and consolidated in complete remission with high-dose chemotherapy, supported by autologous stem cells (AST) and hematopoietic growth factors. The patient remains in complete remission at 34+ months after AST and is surviving disease-free for five years after initial presentation. The case presented here is unusual because of the renal origin and the long remission duration and survival when compared with the usual outcome of adult metastatic PPNET. High-dose chemotherapy may have favorably influenced the outcome in this patient. The case is discussed in the context of the general treatment of metastatic PPNET.

Adult↗
PubMed2003

A phase II study of multimodality treatment for locally advanced cervical cancer: neoadjuvant carboplatin and paclitaxel followed by radical hysterectomy and adjuvant cisplatin chemoradiation.

BACKGROUND: Our aim was to evaluate the efficacy and safety of neoadjuvant chemotherapy followed by radical hysterectomy and adjuvant radiation concurrent with weekly cisplatin for locally advanced cervical carcinoma. PATIENTS AND METHODS: Forty-three patients staged as IB2-IIIB were treated with three 21-day courses of carboplatin (area under the time-concentration curve 6 mg.min/ml) and paclitaxel at 175 mg/m(2) by 3-h infusion both on day 1 followed by radical type III hysterectomy and adjuvant radiation concurrent with 6-weekly doses of cisplatin at 40 mg/m(2). Response rate, resectability, toxicity and survival were evaluated. RESULTS: From December 2000 to June 2001, 43 patients were recruited. All were evaluated for response and toxicity to neoadjuvant chemotherapy. A total of 129 courses were administered. Clinical responses were seen in 41 patients (95%) [95% confidence interval (CI) 89.2% to 100%] with four (9%) complete and 37 (86%) partial. Forty-one patients underwent surgery (resectability 95%); pathologically complete or near-complete responses were seen in seven (17%) and eight (20%), respectively, positive surgical margins in five (12%), and positive pelvic lymph nodes in eight (20%). Twenty-six patients were scheduled for adjuvant chemoradiation. External radiation was delivered for 42.8 days (range 33-61), with a mean dose of 49.3 Gy (range 46-56), and a median of five cisplatin courses (two to six). The mean dose of brachytherapy was 32 Gy (range 25.5-35.6). Neoadjuvant therapy was well-tolerated with neutropenia grade 3 and 4 in 12% and 3% of the courses, respectively. Toxicity to adjuvant chemoradiation was mainly hematological and gastrointestinal, mostly grades 1/2. A total of 39 patients completed all scheduled treatment. At a median follow-up of 21 months (range 3-26), the projected overall survival in the intention-to-treat analysis was 79% (95% CI 62% to 88%). CONCLUSIONS: The triple modality of neoadjuvant chemotherapy followed by radical hysterectomy and adjuvant radiation concurrent with cisplatin is a highly active treatment for locally advanced cervical carcinoma with acceptable toxicity.

Adult↗
PubMed2004

ChromoViz: multimodal visualization of gene expression data onto chromosomes using scalable vector graphics.

SUMMARY: ChromoViz is an R package for the visualization of microarray gene expression data, cross-species and cross-platform comparisons, as well as non-expression genomic data obtained from public databases onto chromosomes. Chromosomal visualization format is proposed for the clear decoupling of the data layer from the procedure layer and the combined visualization of genomic data from heterogeneous data sources. Visualization with Javascript-enabled scalable vector graphics enables interactive visualization and navigation of data objects on the Web. AVAILABILITY: http://www.snubi.org/software/ChromoViz/

Chromosome Mapping↗