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PubMedDate not supplied

Antioxidant action of a new flavonic derivative in acute carbon tetrachloride intoxication.

The antioxidant potential of a new flavonic derivative named conventionally theophylline-rutoside [TR-1722] was estimated by the measurement of G-6-Pase activity (marker enzyme for the endoplasmic reticulum), catalase activity (enzyme involved in the antioxidant defence process), and total -SH groups from the hepatic homogenate, using CCl4 as a free radical generating model. To show changes in the permeability of the hepatocyte membrane, the activity of lactate dehydrogenase (LDH) in plasma was determined. The obtained results suggest that TR-1722 acts by curtailing both lipid peroxidation and alkylation processes.

Animals↗
PubMed2006

[The foundations of computer assisted surgery].

Using navigation systems in general orthopaedic surgery and, in particular, knee replacement is becoming more and more accepted. This paper describes the basic technological concepts of modern computer assisted surgical systems. It explains the variation in currently available systems and outlines research activities that will potentially influence future products. In general, each navigation system is defined by three components: (1) the therapeutic object is the anatomical structure that is operated on using the navigation system, (2) the virtual object represents an image of the therapeutic object, with radiological images or computer generated models potentially being used, and (3) last but not least, the navigator acquires the spatial position and orientation of instruments and anatomy thus providing the necessary data to replay surgical action in real-time on the navigation system's screen.

Computer Graphics↗
PubMed2005

Humanization of a recombinant monoclonal antibody to produce a therapeutic HER dimerization inhibitor, pertuzumab.

Dimerization is essential for activity of human epidermal growth factor receptors (HER1/EGFR, HER2/ErbB2, HER3/ErbB3, and ErbB4) and mediates intracellular signaling events leading to cancer cell proliferation, survival, and resistance to therapy. HER2 is the preferred dimerization partner. Activation of HER signaling pathways may be blocked by inhibition of dimer formation using a monoclonal antibody (MAb) directed against the dimerization domain of HER2. The murine MAb 2C4 that specifically binds the HER2 dimerization domain was cloned as a chimeric antibody, humanized using a computer-generated model to guide framework substitutions, and variants were tested as Fabs. Pharmacokinetics and toxicology were evaluated in rodents and cynomolgus monkeys. Cloning the variable domains of MAb 2C4 into a vector containing human kappa and CH1 domains allowed construction of a mouse-human chimeric Fab. DNA sequencing of the chimeric clone permitted identification of CDR residues. The full-length IgG1 of variant F-10 was equivalent in binding to chimeric IgG1 and was designated pertuzumab (rhuMAb 2C4; Omnitarg). Pertuzumab pharmacokinetics was best described by a two-compartment model with a distribution phase of <1 day, terminal half-life of approximately 10 days, and volume of distribution of approximately 40 mL/kg that approximates serum volume. With the exception of diarrhea, pertuzumab was generally well tolerated in cynomolgus monkeys. Pertuzumab, a recombinant humanized IgG1 MAb, is the first of a new class of agents known as HER dimerization inhibitors. Inhibition of HER dimerization may be an effective anticancer strategy in tumors with either normal or elevated expression of HER2.

Animals↗
PubMed1995

[3-dimensional reconstruction of serial sections in light microscopy].

Computer-based three-dimensional reconstruction of serially cut light microscopic sections is being increasingly used in medical and biological research. Compared with conventional two-dimensional evaluation of histological sections, complex histotopographical relationships and structural details are easy to assess and could be imposingly visualized on the graphics screen. Because of the rapid progress in modern computer hardware, uncomplicated and fast reconstruction systems are available on standard personal computers. Therefore, 3D reconstruction is applicable for a wide range of investigations that warrant 3D exploration. Own results are presented and the principles of 3D reconstruction, as well as the problems and difficulties in this new technique, are discussed. The complex ameboid morphology of megakaryocytes in bone marrow of primary (idiopathic) osteomyelofibrosis is examined with this new method in combination with selective immunohistochemical staining procedures. 3D reconstruction can visualize the complexity of cytoplasmic and nuclear formation impressively. Moreover, the models generated permit exact quantitative measurements of cell morphology. The technique presented is a powerful tool for anatomical-morphological investigations and can furthermore increase our comprehension of complex histomorphological objects.

Bone Marrow↗
PubMed2004

Abdominal aortic aneurysms: virtual imaging and analysis through a remote web server.

The study describes the application of a web-based software in the planning of the endovascular treatment of abdominal aortic aneurysms (AAA). The software has been developed in the framework of a 2-year research project called Aneurysm QUAntification Through an Internet Collaborative System (AQUATICS); it allows to manage remotely Virtual Reality Modeling Language (VRML) models of the abdominal aorta, derived from multirow computed tomography angiography (CTA) data sets, and to obtain measurements of diameters, angles and centerline lengths. To test the reliability of measurements, two radiologists performed a detailed analysis of multiple 3D models generated from a synthetic phantom, mimicking an AAA. The system was tested on 30 patients with AAA; CTA data sets were mailed and the time required for segmentation and measurement were collected for each case. The Bland-Altman plot analysis showed that the mean intra- and inter-observer differences in measures on phantoms were clinically acceptable. The mean time required for segmentation was 1 h (range 45-120 min). The mean time required for measurements on the web was 7 min (range 4-11 min). The AQUATICS web server may provide a rapid, standardized and accurate tool for the evaluation of AAA prior to the endovascular treatment.

Angiography↗
PubMed2001

Computed tomography of the brain in predicting outcome of traumatic intracranial haemorrhage in Malaysian patients.

UNLABELLED: Head injury is a significant economic, social and medical problem all over the world. Road accidents are the most frequent cause of head injury in Malaysia with highest risk in the young (15 to 24 years old). The associated outcomes include good recovery, possibility of death for the severely injured, which may cause disruption of the lives of their family members. It is important to predict the outcome as it will provide sound information to assist clinicians in Malaysia in providing prognostic information to patients and their families, to assess the effectiveness of different modes of treatment in promoting recovery and to document the significance of head injury as a public health problem. RESULTS: A total of 103 cases with intracranial haemorrhage i.e. intracerebral haemorrhage, extradural haemorrhage, subdural haemorrhage, intraventricular haemorrhage, haemorrhagic contusion and subarachnoid haemorrhage, following motor vehicle accidents was undertaken to study factors contributing to either good or poor outcome according to the Glasgow Outcome Scale. Patients below 12 years of age were excluded. The end point of the study was taken at 24 months post injury. The selected variables were incorporated into models generated by logistic regression techniques of multivariate analysis to see the significant predictors of outcome as well as the correlation between the CT findings with GCS. CONCLUSION: Significant predictors of outcome were GCS on arrival in the accident emergency department, pupillary reflex and the CT scan findings. The CT predictors of outcome include ICH, EDH, IVH, present of SAH, site of ICH, volumes of EDH and SDH as well as midline shift.

Accidents, Traffic↗
PubMed2006

Protein engineering of a cold-active beta-galactosidase from Arthrobacter sp. SB to increase lactose hydrolysis reveals new sites affecting low temperature activity.

We examined variants of an especially cold-active beta-galactosidase (BgaS) to better understand features affecting enzyme activity at temperature extremes. We targeted locations corresponding to a region in the LacZ enzyme previously shown to increase activity and decrease thermostability. Changes in this region of BgaS consistently caused the elimination or reduction of activity. A gene (bgaS3) encoding a loss of function variant was subjected to random mutagenesis to restore activity and discover potential interactions important in cold activity. Gene sequences from the resulting library indicated that only two amino acid alterations, E229D and V405A, were required to restore activity. Genes with combinations of these mutations were constructed and their enzymes purified. Enzymes with the E229D/V405A/G803D alterations (BgaS6), or E229D/V405A (BgaS7) had similar thermal optima and thermostabilities as BgaS. BgaS7, however, showed a 2.5-fold increase in catalytic activity at 15 degrees C and hydrolyzed 80% of lactose in skim milk in less than half the time of BgaS at 2.5 degrees C. Computer-generated models predicted that the substitutions at positions 229 and 405 yielded fewer contacts at the enzyme's activating interface. Results from regional saturation mutagenesis supported this hypothesis and suggested that not easily predicted, subtle, cooperative intramolecular interactions contributed to thermal adaptation.

Adaptation, Physiological↗
PubMed2006

Estimation and comparison of ostomy appliance costs with tariffs in Belgium.

This study estimated costs of production and distribution of ostomy appliances, and compared cost estimates with tariffs in Belgium. The cost model took into account manufacturing costs, overhead, R&D, warehousing, profits, and distribution margins. Data were derived from manufacturers, a decomposition of finished products, and interviews with stakeholders. The cost model generated estimated retail prices of euro 2.96 for one-piece appliances, euro 1.62 for two-piece pouches, and euro 2.06 for two-piece flanges. Production and distribution costs accounted for 40 and 60% of retail prices, respectively. Estimated retail prices corresponded well with tariffs for one-piece appliances and for two-piece pouches. For two-piece regular flanges, a substantial difference was observed between the calculated price of euro 2.06 and the tariffs of euro 6.05. In the absence of publicly disclosed information on the cost structure of appliances, estimating ostomy appliance costs is valuable to reimbursement agencies when setting tariffs.

Belgium↗
PubMed1989

Analysis of Ter-Ter enzyme kinetic mechanisms by computer simulation of isotope exchange at chemical equilibrium: development and application of ISOTER, a personal-computer-based program.

A convenient, personal-computer-based program has been developed that allows simulation of isotopic exchange kinetics at chemical equilibrium catalyzed by a three reactant-three product (TerTer) enzyme system: A + B + C integral of P + Q + R. This program, ISOTER, utilizes a rapid algebraic method to calculate the exchange rate between any reactant-product pair as a function of the substrate concentration and avoids altogether the necessity of deriving an explicit (but cumbersome and impractical) equation for exchange rate. ISOTER was used to generate model saturation patterns for 16 different TerTer kinetic mechanisms, varying different combinations of reactant-product pairs in constant ratio at equilibrium: [all substrates], [A, P], [B, Q], and [C, R], while holding the nonvaried components constant. These model studies indicate that virtually every one of these mechanisms can be distinguished from the others. In addition, ISOTER has been used to fit multiple sets of experimental data for Escherichia coli glutamine synthetase, which produced a set of rate constants consistent with the previously proposed "preferred order random" kinetic mechanism.

Computer Simulation↗
PubMed1991

N.m.r. and conformational analysis of the capsular polysaccharide from Streptococcus pneumoniae type 4.

The 1H- and 13C-n.m.r. data on the capsular polysaccharide (1) produced by Streptococcus pneumoniae type 4, the depyruvated polysaccharide (2), and a tetrasaccharide (3a) derived by Smith degradation of 2 were used as constraints on a computer-generated model of the conformation of 1 and to assess the effects of the pyruvic acetal substituent on the conformation. The dynamics of the polysaccharide systems and the influence of the pyruvic acetal were investigated using 13C-n.m.r. relaxation measurements.

Amides↗
PubMed1983

Arterial tonometry: review and analysis.

A review is presented of the field of arterial tonometry and of the problems involved with its application. A second generation model is developed which interprets most of the difficulties encountered in previous experimental work. The model also identifies barriers that must be overcome to allow tonometry to become a practical technique for obtaining measurement of continuous, absolute blood pressure. Problems addressed include those of calibration, positioning sensitivity, design standardization, material properties and vascular loading characteristics. Theoretical and experimental studies provide support for the application of basic biomechanical concepts for solution of these problems and suggest required design features.

Arteries↗
PubMed1984

Pathological left-handedness and ambiguous handedness: a new explanatory model.

A new model is presented which attempts to explain three pathological handedness phenotypes: pathological left-handedness (PLH), pathological right-handedness (PRH) and ambiguous handedness (AH). Revisions in the original model of PLH were prompted in order to account for reports of a raised incidence of both manifest left-handedness and AH in more severely retarded and/or brain-injured populations--namely, autistic. The new model generates specific predictions on the likelihood of different etiological subgroups within these disorders.

Autistic Disorder↗
PubMed1991

Ultraviolet photoreception in carp: microspectrophotometry and behaviorally determined action spectra.

This study demonstrates correlations between u.v. sensitivity and microspectrophotometric absorption spectra determined sequentially for the same group of individuals. We used the heart-rate conditioning technique to measure spectral sensitivity of carp, a species known to have u.v.-sensitive photoreceptors. Mean spectral sensitivity (n = 3) determined with a spectrally-broad background (450 nm long pass filter) revealed a small but consistent u.v. peak (lambda max of 380 nm) in addition to the other long wavelength peaks. An intense blue-green background (490 nm) produced a more prominent u.v. peak (lambda max of 400 nm) when a 450 nm longpass filter was added to the background. Microspectrophotometric measurements of u.v.-sensitive photoreceptors from one individual, which belonged to the group used in the spectral sensitivity experiments, revealed an average lambda max of 377.5 nm (SD +/- 4.5 nm, n = 5 cells). Bleaching and dichroic measurements of these receptors ensured that we were examining typical vertebrate visual pigments and not stable photoproducts. The mean spectral sensitivity points were compared with the u.v. and blue-sensitive visual pigment absorption spectra. A linear subtractive model and ocular media absorption were used in this comparison for the various photic conditions used in the heart-rate conditioning experiments. The model successfully described the sensitivity of the test fish in two cases but in a third case there was some discrepancy. The model generated curve was broader than the spectral sensitivity of the u.v.-sensitive cone mechanism on the shortwave side even though the ocular media corrections had been accounted for.

Animals↗
PubMed1989

Birth, death and taxes.

"This paper analyzes the effects of lump-sum tax policy in an overlapping generations model in which consumers have uncertain longevity. It extends previous analyses by considering the case in which private insurance arrangements are actuarially unfair. In addition, it considers the polar case of actuarially fair insurance and the polar case of no insurance. A general condition for debt neutrality is derived. This condition depends explicitly on the degree of actuarial unfairness in insurance and on the extent to which parents care about the utility of their children."

Americas↗
PubMed1995

Urinary excretion kinetics of 1-hydroxypyrene in volunteers exposed to pyrene by the oral and dermal route.

Two well-informed human volunteers were exposed to 500 micrograms pyrene by ingestion and by dermal application, in two separate experiments. Urinary measurements of 1-hydroxypyrene (1-OHP) were performed on all micturitions taken at intervals of 0.5-4 h for a total period of 48 h after dosing. Following the absorption phase, 1-OHP is excreted with a first order apparent half-life of approximately 12 h for both volunteers and both exposure routes. These results compare well with other previously published studies. A more refined analysis of the data was performed using a two-compartment toxicokinetic model for 'pyrene' (its fraction eventually excreted as 1-OHP). As it was found that a classical first-order system did not adequately fit the data, a non-linear term was introduced in the model for the elimination of urinary 1-OHP. Computer iteration performed on the oral absorption data allowed an estimation of various toxicokinetic parameter values. The mean intercompartmental exchange (k12 and k21) and elimination coefficients were 0.010, 0.006 and 0.012 min-1, respectively. The first two values compare well with those previously published for the rat, whereas the latter is smaller in humans. These values were used to satisfactorily simulate the experimental data for both routes of exposure, adjusting only for kabs which was estimated at 0.014 and 0.0029 min-1 for the oral and dermal exposure, respectively. The proposed model generates new hypotheses on the metabolism of pyrene. The information collected will contribute to the validation of the utilisation of 1-OHP as a biological indicator of exposure to pyrene.

Administration, Cutaneous↗
PubMed1995

Regulation of nutrient intake in humans: a theory based on taste and smell.

Oral and pharyngeal recognition of the chemical structure of physiologically relevant nutrients is proposed as a mechanism for regulating nutrient intake. Taste buds and olfactory receptors are proposed as the primary sites of recognition. Oral and pharyngeal sensory signals may be sufficient for producing satiation and termination of a meal provided the initiation of the meal is triggered by the body's need to replenish a deficient nutrient. A discussion of the impact of disturbances of normal regulation and some questions this model generates are also incorporated.

Eating↗
PubMed1985

IgA1 protease cleaves heavy chains independently in dimeric human IgA1.

Bacterial IgA1 proteases have substrate specificity for human IgA1 immunoglobulin, and cleave both the heavy (alpha) chains where they are paired by disulfide bonds in the hinge region. To determine if the close apposition of the alpha chains allows a single enzyme-substrate-binding event to cleave both hinge region peptides we quantitated the relative levels of intermediate products during the course of complete hydrolysis of an IgA1 paraprotein. The substrate had four Fab regions, analogous to a secretory IgA dimer. The experimental data were then compared to computer-generated models in which various levels of cooperativity among Fab regions were tested. The results most closely conformed to a model in which each individual alpha chain is proteolyzed independently, without regard to the total number of hinge region peptides available in the substrate IgA1. These results will be used to guide the design of IgA1 hinge region peptide analogues as IgA1 protease inhibitors.

Autoradiography↗
PubMed1988

Oxygen activation and ligand binding by pure heme-octapeptide microperoxidase-8 (MP-8).

The rapid, efficient preparation of pure microperoxidase-8 (MP-8) is described. Ligand binding studies confirm that MP-8 is monomeric in alkaline solution. It is shown that the monomeric MP-8 activates oxygen in a similar manner to that already reported for alkaline hemin, establishing the octapeptide as a possible second generation model for the oxygen activation/insertion reactions of the cytochrome P-450.

Animals↗