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PubMed1983

External skeletal fixation using methylmethacrylate. Current technique, clinical results, and indications.

External skeletal fixation using self-curing acrylic resin was applied by inserting A-O cortical screws into the diaphyseal region and A-O cancellous screws into the epiphyseal and/or metaphyseal regions. The position of the screws was designed to secure three-dimensional fixation. Points of insertion are selected that avoid infected bone, open wounds, thick muscles, and skin that is relatively mobile during joint motion. After reduction the acrylic resin rather than conventional metal linking devices is used for fixation of the screws. Once the fixation is completed, it is adjustable and so rigid that exercises for joint function are possible. The apparatus is light in weight and sufficiently compact to fit under clothing. In the 204 patients treated by this method, open tibial fractures occurred in 123; nonunion or delayed union in 28; metaphyseal and epiphyseal fractures in 30; femoral fractures in ten children; and miscellaneous fractures and other conditions in 13. Nearly all of the operations were successful. Three patients had refractures after removal of the fixation device.

Adult↗
PubMed1994

GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell'infarto Miocardico.

GISSI-3 is a multicentre randomised clinical trial to assess the efficacy of lisinopril, transdermal glyceryl trinitrate (GTN), and their combination in improving survival and ventricular function after acute myocardial infarction (AMI). Between June, 1991, and July, 1993, 19,394 patients were randomised from 200 coronary care units in Italy. Eligible patients presented within 24 h of symptom onset and had no clear indications for or against the study treatments. In a factorial design patients were randomly assigned 6 weeks of oral lisinopril (5 mg initial dose and then 10 mg daily) or open control as well as nitrates (intravenous for the first 24 h followed by transdermal GTN 10 mg daily) or open control. Complete clinical data and 6-week follow-up were available for 18,895 (97.4%) patients randomised. Two-dimensional echocardiographic data were available for 14,209 patients. Overall 6-week mortality was 6.7%. Lisinopril, started within 24 h from AMI symptoms, produced significant reductions in overall mortality (odds ratio 0.88 [95% CI 0.79-0.99]) and in the combined outcome measure of mortality and severe ventricular dysfunction (0.90 [0.84-0.98]). In the same trial the systematic administration of transdermal GTN did not show any independent effect on the same outcome measures (0.94 [0.84-1.05] and 0.94 [0.87-1.02]). Systematic combined administration of lisinopril and GTN also produced significant reductions in overall mortality (0.83 [0.70-0.97]) and in the combined endpoint (0.85 [0.76-0.94]). The favourable effect of lisinopril alone or with GTN was clear also in the predefined high-risk populations (elderly patients and women) for the combined endpoint. These findings were obtained in a population intensively exposed to recommended treatments (thrombolysis 72%, beta-blockade 31%, and aspirin 84%); non-protocol treatment with angiotensin-converting-enzyme inhibitors and nitrates was allowed for specific clinical indications. No excess of unfavourable clinically relevant events in the treated groups was reported.

Administration, Cutaneous↗
PubMedDate not supplied

[Electrophoretic characteristics of integrin++ beta1 subunit from human smooth muscles].

Total fraction of beta 1 integrin family was isolated from human smooth muscle by affinity chromatography on immobilized anti-beta 1 monoclonal antibodies. SDS-PAGE analysis and subsequent immunoblotting demonstrated that integrin samples contain unknown before high molecular mass (205 kD-nonreduced and 230 kD-reduced) material immunologically related to beta 1 integrin subunit. One dimensional peptide mapping showed that the 205 kD protein is not a novel beta 1 related integrin subunit, but a beta 1 integrin subunit dimer. Reduction of electrophoretic samples with dithiothreitol led to the removal of the major part of the beta 1 immunoreactive material from 205 kD to 130 kD region, indicating a disulfide nature of B1 integrin subunit dimer. The 230 kD protein turned out to be an only partly reduced beta 1 integrin disulfide bonded dimer. Possible in vivo existence of the disulfide bonded dimer and oligomer integrin forms is discussed.

Electrophoresis, Polyacrylamide Gel↗
PubMed2004

Carbonylation of glycolytic proteins is a key response to drug-induced oxidative stress and apoptosis.

Recent work has highlighted the importance of protein post-translational modifications such as phosphorylation (enzymatic) and nitrosylation (nonenzymatic) in the early stages of apoptosis. In this study, we have investigated the levels of protein carbonylation, a nonenzymatic protein modification that occurs in conditions of cellular oxidative stress, during etopside-induced apoptosis of HL60 cells. Within 1 h of VP16 treatment, a number of proteins underwent carbonylation due to oxidative stress. This was inhibited by the antioxidant N-acetyl-L-cysteine. Among the proteins found to be carbonylated were glycolytic enzymes. Subsequently, we found that the rate of glycolysis was significantly reduced, probably due to a carbonylation mediated reduction in enzymatic activity of glycolytic enzymes. Our work demonstrates that protein carbonylation can be rapidly induced through cytotoxic drug treatment and may specifically inhibit the glycolytic pathway. Given the importance of glycolysis as a source of cellular ATP, this has severe implications for cell function.

Acetylcysteine↗
PubMed2003

Smoothing Monte Carlo calculated dose distributions by iterative reduction of noise.

A smoothing algorithm based on an optimization procedure is presented and evaluated for single electron and photon beams and a full intensity modulated radiation therapy (IMRT) delivery. The algorithm iteratively reduces the statistical noise of Monte Carlo (MC) calculated dose distributions. It is called IRON (iterative reduction of noise). By varying the dose in each voxel, the algorithm minimizes the second partial derivatives of dose with respect to X, Y and Z. An additional restoration term ensures that too large dose changes are prevented. IRON requires a MC calculated one-dimensional or three-dimensional dose distribution with or without known statistical uncertainties as input. The algorithm is tested using three different treatment plan examples, a photon beam dose distribution in water, an IMRT plan of a real patient and an electron beam dose distribution in a water phantom with inhomogeneities. It is shown that smoothing can lead to an additional reduction of MC calculation time by factors of 2 to 10. This is especially useful if MC dose calculation is part of an inverse treatment planning system. In addition to this, it is shown that smoothing a noisy dose distribution may introduce some bias into the final dose values by converting the statistical uncertainty of the dose distribution into a systematic deviation of the dose value.

Algorithms↗
PubMed2003

Proteomic analysis of mdx skeletal muscle: Great reduction of adenylate kinase 1 expression and enzymatic activity.

To investigate the pathophysiological events of Duchenne muscular dystrophy, we analyzed alterations of protein expression in hindlimb muscles of three month old mdx mice using two-dimensional gel electrophoresis and mass spectrometry. About 40 differentially expressed proteins from the cytosolic fraction and 20 from the microsomal fraction of mdx hindlimb muscles were identified. Among these altered proteins, adenylate kinase 1 (AK 1) was particular interesting because its decrease in abundance was so dramatic (> four-fold). Enzymatic assays demonstrated that AK 1 activity was also decreased in mdx mice. Furthermore, the expression and enzymatic activity of AK 1 were consistently reduced in mdx mice at one and six months of age, suggesting a direct relationship between the lack of dystrophin and alteration of AK 1. Along with AK 1, creatine kinase (CK) provides a major pathway for regulation of nucleotide ratios and energy metabolism in muscles. To gain a better understanding of mechanisms of energy metabolism, we also investigated CK activities in these mdx mice at different ages. Our results suggested that decreased AK 1 expression and activity might result in redistribution of energy flow through the alternative CK system, thus a compensatory potential might limit cellular energy failure in mdx skeletal muscle.

Adenylyl Cyclases↗
PubMed1981

Basal cell pseudopodia in cervical intraepithelial neoplasia; progressive reduction of number with severity: a morphometric quantification.

An application of a morphometric model is used to study the stroma epithelial interface in human cervical epithelium. This model derived by Okagaki and associates estimates from two dimensional transmission electron photomicrographs the number of basal cell pseudopodia per basal cell. The investigation of the full spectrum of cervical intraepithelial neoplasia (CIN) focusing on the basal cell-stroma interface with the "multiple cell-single section" model is discussed. Significant decreases in histopathologic grades of CIN are noted in the number of pseudopodia per basal cell (N) and the ratio (F) of the area of the stems of pseudopodia to the area of the base of the basal cell.

Carcinoma in Situ↗
PubMed2001

[Estimation of the probability of mediastinal involvement: a statistical definition of the clinical target volume for 3-dimensional conformal radiotherapy in non-small-cell lung cancer?].

PURPOSE: Conformal irradiation of non-small cell lung carcinoma (NSCLC) is largely based on a precise definition of the nodal clinical target volume (CTVn). The reduction of the number of nodal stations to be irradiated would render tumor dose escalation more achievable. The aim of this work was to design an mathematical tool based on documented data, that would predict the risk of metastatic involvement for each nodal station. METHODS AND MATERIAL: From the large surgical series published in the literature we looked at the main pre-treatment parameters that modify the risk of nodal invasion. The probability of involvement for the 17 nodal stations described by the American Thoracic Society (ATS) was computed from all these publications and then weighted according to the French epidemiological data. Starting from the primitive location of the tumour as the main characteristic, we built a probabilistic tree for each nodal station representing the risk distribution as a function of each tumor feature. From the statistical point of view, we used the inversion of probability trees method described by Weinstein and Feinberg. RESULTS: Taking into account all the different parameters of the pre-treatment staging relative to each level of the ATS map brings up to 20,000 different combinations. The first chosen parameters in the tree were, depending on the tumour location, the histological classification, the metastatic stage, the nodal stage weighted in function of the sensitivity and specificity of the diagnostic examination used (PET scan, CAT scan) and the tumoral stage. A software is proposed to compute a predicted probability of involvement of each nodal station for any given clinical presentation. CONCLUSION: To better define the CTVn in NSCLC 3DRT, we propose a software that evaluates the mediastinal nodal involvement risk from easily accessible individual pre-treatment parameters.

Carcinoma, Non-Small-Cell Lung↗
PubMed1990

Human type VI collagen: isolation and characterization of alpha 1 and alpha 2 chains by two-dimensional preparative gel electrophoresis.

Two 140 kDa collagenous glycoproteins were isolated from 5 M guanidinium chloride extracts of human uterine leiomyoma by two-dimensional preparative gel electrophoresis. The glycoproteins represented the major concanavalin A binding fraction of the extract and were also present in adult human skin. On two-dimensional gel electrophoresis the glycoproteins appeared as elongated spots, indicating variations of their isoelectric points from 5 to 6. These glycoproteins were disulfide-bonded components of high molecular mass protein and, after reduction, became sensitive to collagenase treatment that generated peptides corresponding in size to those of the noncollagenous domains of type VI collagen. Antisera raised against these purified glycoproteins reacted with either pepsin-derived alpha 1(VI) or pepsin-derived alpha 2(VI) chains but not with alpha 3(VI) chain of human type VI collagen. Reciprocally, these glycoproteins reacted with monoclonal antibodies against type VI collagen. These results indicate that the glycoproteins represent the integral alpha 1 and alpha 2 chains of type VI collagen. The globular domains of alpha 1(VI) and alpha 2(VI) chains remaining after collagenase treatment appeared on two-dimensional gel electrophoresis as elongated spots, suggesting that the noncollagenous portions determine the well known microheterogeneity of the molecule. The differences in isoelectric points between and within alpha chains may facilitate the formation of microfibrillar network.

Amino Acids↗
PubMed2003

Stabilization of hydrodynamic flows by small viscosity variations.

Motivated by the large effect of turbulent drag reduction by minute concentrations of polymers, we study the effects of a weakly space-dependent viscosity on the stability of hydrodynamic flows. In a recent paper [Phys. Rev. Lett. 87, 174501, (2001)], we exposed the crucial role played by a localized region where the energy of fluctuations is produced by interactions with the mean flow (the "critical layer"). We showed that a layer of a weakly space-dependent viscosity placed near the critical layer can have a very large stabilizing effect on hydrodynamic fluctuations, retarding significantly the onset of turbulence. In this paper we extend these observations in two directions: first we show that the strong stabilization of the primary instability is also obtained when the viscosity profile is realistic (inferred from simulations of turbulent flows with a small concentration of polymers). Second, we analyze the secondary instability (around the time-dependent primary instability) and find similar strong stabilization. Since the secondary instability develops around a time-dependent solution and is three dimensional, this brings us closer to the turbulent case. We reiterate that the large effect is not due to a modified dissipation (as is assumed in some theories of drag reduction), but due to reduced energy intake from the mean flow to the fluctuations. We propose that similar physics act in turbulent drag reduction.

Journal Article↗
PubMed2006

Runx2 is a target of mechanical unloading to alter osteoblastic activity and bone formation in vivo.

Molecular mechanisms underlying unloading-induced reduction of bone formation have not yet been fully understood. In vitro, Runx2 has been suggested to be involved in mechanical signaling in osteoblasts. However, the roles of Runx2 in vivo during the bone response to mechanical stimuli have not yet been known. The purpose of this paper was to examine the roles of Runx2 in unloading-induced bone loss in vivo. Tail suspension was conducted for 2 wk using 9- to 11-wk-old Runx2 heterozygous knockout mice (Runx2(+/-)) and wild-type (Wt) littermates. Bones were subjected to two-dimensional micro-x-ray computed tomography, bone histomorphometry and RT-PCR analyses. Loss of half Runx2 gene dosage-exacerbated unloading-induced bone loss in trabecular and cortical envelopes. Unloading-induced reduction in mineral apposition rate and bone formation rate in cortical bone as well as trabecular bone was exacerbated in Runx2(+/-) mice, compared with Wt mice. Bone resorption parameters were not significantly affected by unloading or Runx2(+/-) genotype. Basal Runx2 and osterix mRNA levels in bone were reduced by 50% in Wt, whereas unloading in Runx2(+/-) mice did not further alter Runx2 and osterix mRNA levels. In contrast, osteocalcin mRNA levels were reduced by unloading, regardless of Runx2 gene dosage. These data demonstrated that full Runx2 gene dosage is required for maintaining normal function of osteoblasts in mechanical unloading or nonphysiological condition. Finally, we propose Runx2 as a critical target gene in unloading to alter osteoblastic activity and bone formation in vivo.

Amino Acids↗
PubMed2002

Microenvironments and microbial community structure in sediments.

The aim of this study was to explore the potential of a combined chemical and microbiological approach as part of a study of organic carbon oxidation processes in sediments. An assessment of microbiological diversity using molecular techniques was carried out in combination with high resolution chemical measurements at the sediment-water interface of a coastal lagoon affected by eutrophication in autumn 2000. There was a 0.2 mm overlap between the O2 and H2S profiles. pH showed a maximum just above the sediment-water interface coinciding with an oxygen maximum, suggesting photosynthetic activity, and a minimum coinciding with the O2-H2S interface. The redox potential was high in bottom water and surface sediment, reflecting the presence of oxygen and oxides, and reached low values after a step-wise decrease at -18 mm. Reduction of Fe occurred within the biofilm at the O2-H2S interface and was mostly due to reduction by H2S. The elevated concentrations of dissolved Mn in the oxic water may have been caused either by in situ production within organic aggregates or lateral water flow from sites nearby at which Mn2+ diffuses out of the sediment. Sequences related to sulphur chemolitotrophs were retrieved from the biofilm samples, which is consistent with the small overlap between O2 and H2S observed in this biofilm. Although the resolution of techniques used was different, sequencing results were consistent with chemical data in delineating the same horizons according to redox, pH or ecological properties.

Bacteria↗
PubMedDate not supplied

Application of electrochemical reactors for industrial waste-water treatment.

The effectiveness of electrochemical reactors for industrial wastewater treatment has been improved since three-dimensional electrodes have been introduced; in fact, limitations of mass transfer can arise, due to the low concentrations of pollutants which may be involved in the process. Three-dimensional electrodes offer a very high electrode area per unit electrode volume and they can act as turbulence promoters or give rise to high linear electrolyte velocity, resulting in high values of mass transport coefficient. However, careful selection of operative parameters is needed in order to obtain high performance. This paper examines the results obtained in our laboratory on the cathodic reduction of copper at RVC electrodes; in particular the interference of dissolved oxygen is studied during the removal of copper from extremely diluted solutions (C < 10 ppm). Some results are also discussed on the removal of organic pollutants by electrochemical oxidation at three-dimensional anode consisting of a fixed bed of carbon pellets.

Copper↗
PubMed2004

Possible association of GroES and antigen 85 proteins with heat resistance of Mycobacterium paratuberculosis.

Conflicting reports on the heat resistance of Mycobacterium paratuberculosis prompted an examination of the effect of culture medium on this property of the organism. M. paratuberculosis was cultured in three types of media (fatty acid-containing medium 7H9-OADC (oleic acid-albumin-dextrose-catalase supplement) and glycerol-containing media WR-GD and 7H9-GD [glycerol-dextrose supplement]) at pH 6.0. M. paratuberculosis grown under these three culture conditions was then tested for heat resistance in distilled water at 65 degrees C. Soluble proteins and mycolic acids of M. paratuberculosis were evaluated by two-dimensional electrophoresis (2-DE) and thin-layer chromatography (TLC), respectively. The type of culture medium used significantly affected the heat resistance of M. paratuberculosis. The decimal reduction times at 65 degrees C (D(65 degrees C) values; times required to reduce the concentration of bacteria by a factor of 10 at 65 degrees C) for M. paratuberculosis strains grown in 7H9-OADC were significantly higher than those for the organisms grown in WR-GD medium (P < 0.01). When the glycerol-dextrose supplement of WR was substituted for the fatty acid supplement (OADC) in 7H9 medium (resulting in 7H9-GD), the D(65 degrees C) value was significantly lower than that for the organism grown in 7H9-OADC medium (P = 0.022) but higher than that when it was cultured in WR-GD medium (P = 0.005). Proteomic analysis by 2-DE of soluble proteins extracted from M. paratuberculosis grown without heat stress in the three media (7H9-OADC, 7H9-GD, and WR-GD) revealed that seven proteins were more highly expressed in 7H9-OADC medium than in the other two media. When the seven proteins were subjected to matrix-assisted laser desorption ionization-mass spectrometric analysis, four of the seven protein spots were unidentifiable. The other three proteins were identified as GroES heat shock protein, alpha antigen, and antigen 85 complex B (Ag85B; fibronectin-binding protein). These proteins may be associated with the heat resistance of M. paratuberculosis. Alpha antigen and Ag85B are both trehalose mycolyltransferases involved in mycobacterial cell wall assembly. TLC revealed that 7H9-OADC medium supported production of more trehalose dimycolates and cell wall-bound mycolic acids than did WR-GD medium. The present study shows that in vitro culture conditions significantly affect heat resistance, cell wall synthesis, and protein expression of M. paratuberculosis and emphasize the importance of culture conditions on in vitro and ex vivo studies to estimate heat resistance.

Amino Acid Sequence↗
PubMed1989

Characterization of the CA125 antigen secreted from a newly established human ovarian cancer cell line (SHIN-3).

A cell line (designated SHIN-3) was established from a 56-year-old Japanese woman diagnosed as having serous cystadenocarcinoma of the ovary. SHIN-3 produced the tumor marker, CA125. When samples were subjected to one-dimensional gel electrophoresis followed by immunoblotting with anti-CA125 antibody, antigen binding appeared in the low-molecular-mass fraction around 50 KDa as well as in the high-molecular-mass fraction (more than 200 KDa). Subsequent resolution of this lower-molecular-mass component by two-dimensional gel electrophoresis gave rise to bands of 49 KDa near an isoelectric point of 7.3. Treatment of the CA125 antigen with 10 mM periodic acid resulted in no loss of activity. However, reduction and alkylation in 6 M guanidine-HCl or treatment at 100 degrees C for 20 min resulted in complete loss of activity. Treatment with various glycosidases did not inhibit activity, whereas digestion with proteases (except for papain) produced complete loss of activity, suggesting that the CA125 antigenic determinant is composed of conformationally dependent peptides.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed2006

Comparison of forward planning with automated inverse planning for three-dimensional conformal radiotherapy of non-small cell lung cancer without IMRT.

The forward and inverse treatment plans of 10 patients with lung cancer were compared in terms of PTV coverage, sparing of normal lung and time required to generate a plan. The inverse planning produced as good treatment plans as an experienced dosimetrist with considerable reduction in staff time. When translated to other complex sites, inverse non-IMRT planning may have considerable impact on manpower requirements.

Algorithms↗
PubMed2005

Parallel statistical image reconstruction for cone-beam x-ray CT on a shared memory computation platform.

Statistical reconstruction methods offer possibilities of improving image quality as compared to analytical methods, but current reconstruction times prohibit routine clinical applications. To reduce reconstruction times we have parallelized a statistical reconstruction algorithm for cone-beam x-ray CT, the ordered subset convex algorithm (OSC), and evaluated it on a shared memory computer. Two different parallelization strategies were developed: one that employs parallelism by computing the work for all projections within a subset in parallel, and one that divides the total volume into parts and processes the work for each sub-volume in parallel. Both methods are used to reconstruct a three-dimensional mathematical phantom on two different grid densities. The reconstructed images are binary identical to the result of the serial (non-parallelized) algorithm. The speed-up factor equals approximately 30 when using 32 to 40 processors, and scales almost linearly with the number of cpus for both methods. The huge reduction in computation time allows us to apply statistical reconstruction to clinically relevant studies for the first time.

Algorithms↗
PubMedDate not supplied

Left anterior subregion of orbitofrontal cortex volume reduction and impaired organizational strategies in obsessive-compulsive disorder.

The orbitofrontal cortex (OFC) may be involved in the clinical and cognitive expressions of obsessive-compulsive disorder (OCD) and is a heterogenous region with respect to its cytoarchitecture, function and connectivity. This study was designed to examine the morphological abnormality of the anterior subregion of OFC and its relationship to clinical symptoms and cognitive performance in patients with OCD. We divided the OFC into anterior and posterior subregions using an external landmark and measured the gray matter volumes of each by three-dimensional magnetic resonance imaging in age- and sex-matched groups, which consisted of 34 OCD and 34 normal volunteers. Clinical and cognitive evaluations were completed using Yale-Brown Obsessive Compulsive Scale (YBOCS) and four sets of neuropsychological tests that assessed executive functions and visual memory. Volume reduction of the left anterior OFC was observed in patients with OCD versus normal controls. Also, a significant positive correlation was found between left anterior OFC gray matter volume and the copy score of the Rey-Osterrieth Complex Figure Test in patients with OCD. These results suggest that left anterior subregion volume reduction of the OFC may be related to impaired organizational strategies in patients with OCD.

Adult↗