bluuebunny/crossref_metadata_2025 huggingface dataset:
Microarrays of 41 Human Tumor Cell Lines for the Characterization of New Molecular Targets: Expression Patterns of Cathepsin B and the Transferrin Receptor
Authors: Wirth Gregory J. , Schandelmaier Kathrin , Smith Victoria , Burger Angelika M. , Fiebig Heinz-Herbert
Published: March 2007

In recent years the use of the microarray technology has allowed the identification of numerous cancer-related genes and proteins. Today anticancer drug discovery is mainly target driven, which requires the characterization of molecular targets in existing cell lines or xenograft models. However, this analysis is time consuming and labor intensive. In order to ease this bottleneck, we have established tissue microarrays of 41 human tumor cell lines on glass slides. The purpose of our study was to (a) establish a simple and efficient method for cell line microarray construction, (b) apply the resulting array to the profiling of cathepsin B and transferrin receptor by immunohistochemistry and (c) verify the results in separate Western blot analyses. Ten to twenty million (1–2 × 107) cells were harvested without trypsinization and fixed with Bouin’s solution containing 8% formalin. Cell pellets 2–5 mm in diameter were embedded in paraffin. Microarrays were assembled using a tissue arrayer. Pellet biopsies 0.6 cm in diameter were taken and arrayed in duplicate in a new recipient paraffin block. About 60 slides can be obtained from one block. Citrate buffer was used for antigen retrieval. Expression of cathepsin B was granular and located in the cytoplasm. High cathepsin B levels were detected in 2 melanomas (MEXF 514L and MEXF 276L) and in the renal cell line RXF 486L. Twenty-five cell lines showed only minimal positivity. Nine cell lines of leukemia and lymphoma, breast, ovarian, prostate and renal cancer origin were positive for the transferrin receptor, while 32 cell lines were negative. Western blotting confirmed the results obtained by immunohistochemistry. Using these cell line microarrays, cell lines overexpressing a target of interest can be selected for in vitro evaluation of specific inhibitors.
Differential Dropout among SNP Genotypes and Impacts on Association Tests
Authors: Hao Ke , Cawley Simon
Published: March 2007

Background: Current biotechnologies are able to achieve high accuracy and call rates. Concerns are raised on how differential performance on various genotypes may bias association tests. Quantitatively, we define differential dropout rate as the ratio of no-call rate among heterozygotes and homozygotes. Methods: The hazard ofdifferential dropout is examined for population- and family-based association tests through a simulation study. Also, we investigate detection approaches such as Hardy-Weinberg Equilibrium (HWE) and testing for correlation between sample call rate and sample heterozygosity. Finally, we analyze two public datasets and evaluate the magnitudes of differential dropout. Results: In case-control settings, differential dropout has negligible effect on power and odds ratio (OR) estimation. However, the impact on family-based tests range from minor to severe depending on the disease parameters. Such impact is more prominent when disease allele frequency is relatively low (e.g., 5%), where a differential dropout rate of 2.5 can dramatically bias OR estimation and reduce power even at a decent 98% overall call rate and moderate effect size (e.g., ORtrue = 2.11). Both of the two public datasets follow HWE; however, HapMap data carries detectable differential dropout that may endanger family-based studies. Conclusions: Case-control approach appears to be robust to differential dropout; however, family-based association tests can be heavily biased. Both of the public genotype data show high call rate, but differential dropout is detected in HapMap data. We suggest researchers carefully control this potential confounder even using data of high accuracy and high overall call rate.
Various Dietary Protein Intakes and Progression of Renal Failure in Spontaneously Hypercholesterolemic Imai Rats
Authors: Liang Xiang-Ming , Otani Haruhisa , Zhou Qin , Tone Yoshinori , Fujii Ryoichi , Mune Masatoshi , Yukawa Susumu , Akizawa Tadao
Published: March 2007

Background/Aim: Dietary protein restriction is known to be beneficial in the preservation of the renal function in patients with chronic renal failure. Recently, the effect of varying quantity and quality of dietary protein intakes was also studied. This study investigates the effects of different dietary animal proteins on renal function in spontaneously hypercholesterolemic Imai rats that exhibit renal lesions similar to human focal and segmental glomerulosclerosis. The sources of proteins were from casein, pork, and fish. Primary concern was the effect of fish meat protein, because the effects of fish oil are well reported. To examine whether remnants of fish oil affect the experimental results, semi-defatted fish meat and fully defatted fish meat were prepared for these experiments. Methods: Forty-two Imai rats were placed on diets containing casein, defatted pork meat, semi-defatted fish meat, or defatted fish meat as a protein sources from 10 to 22 weeks of age. Twenty-four hour urine collections were obtained along with measurements of systolic blood pressure and drawing blood from the tail artery every 4 weeks. Finally, the kidneys were removed and prepared for histological study. Results: The semi-defatted fish meat diet retarded the rise of plasma cholesterol, virtually completely prevented the development of hypertriglyceridemia, and slowed the progression of proteinuria, renal function failure, and glomerular injury as compared with the control casein diet. However, the fully defatted fish meat diet led to renal failure at the same rate as the casein diet. The defatted pork diet group exhibited a higher creatinine clearance at the end of the experiments as compared with the casein and the fully defatted fish meat diet groups. Conclusions: These data suggest that an important determinant of the protective effects of the semi-defatted fish meat diet was related to the prevention of hypercholesterolemia and hypertriglyceridemia by the remaining fish oil. Fish meat protein itself did not indicate superior beneficial effects in the regression of the renal function in Imai rats as compared with casein protein, and defatted pork showed better results than casein and fully defatted fish meat.
The Combination of ACE Inhibition plus Sympathetic Denervation Is Superior to ACE Inhibitor Monotherapy in the Rat Renal Ablation Model
Authors: Hamar Peter , Kokeny Gabor , Liptak Peter , Krtil Jan , Adamczak Marcin , Amann Kerstin , Ritz Eberhard , Gross Marie-Luise
Published: March 2007

Background: The blood pressure-independent renoprotective actions of the blockade of the renin-angiotensin and the sympathetic nervous system are well documented, but monotherapies fail to completely abrogate progression. We investigated whether combined inhibition of the two systems provides additive renoprotection. Methods: After subtotal nephrectomy (SNX) or sham operation, rats underwent resection of dorsal roots, i.e. rhizotomy or sham rhizotomy. Subsequently, they received tap water or quinapril in drinking water for 16 weeks (n = 18/group). Albuminuria, blood pressure and kidneys were assessed (morphometry, immunohistochemistry). Results: At the end of the study telemetric blood pressure in SNX was 118 ± 16 mm Hg, in SNX + rhizotomy 110 ± 10 mm Hg, in SNX + quinapril 103 ± 9 mm Hg and in SNX + quinapril + rhizotomy 95 ± 7 mm Hg. Albuminuria in the respective groups was 169 ± 75, 86 ± 45, 15 ± 23 and 5 ± 4 mg/24 h. The glomerulosclerosis index was 1.40 ± 0.6, 0.80 ± 0.23, 0.37 ± 0.16 and 0.31 ± 0.15 (p < 0.001). Only combined intervention caused significant reduction of the glomerular volume and podocyte hypertrophy. The lowest indices for nitrotyrosine, NOS-1 (nNOS), TGF-β and interstitial collagen were seen with combined interventions (p < 0.05). Conclusion: In angiotensin-converting enzyme inhibitor-treated SNX animals, abrogation of sympathetic overactivity provides additional renoprotection and less nitro-oxidative stress of podocytes than single interventions. The added benefits were partially blood pressure independent.
Reduction in Platelet Activation by Citrate Anticoagulation Does Not Prevent Intradialytic Hemodynamic Instability
Authors: Gritters Mareille , Borgdorff Piet , Grooteman Muriel P.C. , Schoorl Marianne , Schoorl Margreet , Bartels Piet C.M. , Tangelder Geert Jan , Nubé Menso J.
Published: March 2007

Background: The etiology of intradialytic hemodynamic instability is multifactorial. Of the various factors involved, a rise in core temperature seems to be crucial. In this respect, the bioincompatibility of hemodialysis (HD) treatment might play an important role. The application of cool dialysate reduces the number of periods of intradialytic hypotension (IDH) considerably. In rats, roller pump perfusion caused hypotension by shear stress induced platelet aggregation and subsequent serotonin release. During clinical HD, citrate anticoagulation abolished platelet activation almost completely. Hence, citrate anticoagulation might reduce IDH, whereas the beneficial effect of cool dialysate might be partly explained by reduced platelet activation. Methods: In the present study, blood pressure, IDH episodes, platelet activation, platelet aggregation, and serotonin release were studied crossover in 10 patients during HD with dalteparin anticoagulation at normal and low dialysate temperatures and during HD with citrate. Results: Citrate strongly reduced platelet activation, but did not improve IDH. The blood pressure was best preserved during cool-temperature HD, despite manifest platelet activation. Platelet activation was not accompanied by a rise in the plasma serotonin concentration. Conclusions: Three major conclusions can be drawn: (1) it is unlikely that platelet activation and subsequent serotonin release underlie IDH in the clinical situation; (2) the protective effects of cool dialysate on IDH appear to be independent of HD-induced platelet activation, and (3) extrapolating results from rat experiments to the human situation requires uppermost prudence.
Relationship between Nocturnal Growth Hormone Concentrations, Serum IGF-I/IGFBP-3 Levels, Insulin Sensitivity and GH Receptor Allelic Variant in Small for Gestational Age Children
Authors: Mericq Verónica , Román Rossana , Iñiguez Germán , Angel Bárbara , Salazar Teresa , Avila Alejandra , Perez-Bravo Francisco , Cassorla Fernando
Published: March 2007

Growth hormone may help to increase final height in patients with short stature, but its efficacy is variable. It has been recently reported that the isoform of the GH receptor (GHR) that lacks exon 3 (d3-GHR) is associated with a greater growth response to GH therapy. We hypothesized that nocturnal growth hormone concentrations, basal IGF-I and IGFBP-3 levels, and insulin sensitivity might show variations among individuals depending on their GHR allelic variant. To test this hypothesis, we studied 38 prepubertal LBW children with nocturnal GH concentrations, IGF-I and IGFBP-3 levels and insulin sensitivity during OGTT and Insulin test. The GHR allelic variant was analyzed through multiplex PCR analysis in DNA from peripheral leukocytes. Characteristics of the overnight GH secretion [(mean GH: 6.8 ± 0.6 vs. 6.2 ± 0.5 ng/ml), (AUC: 3,227 ± 280 vs. 2,908 ± 212 ng/ml·min), (peak number: 4.4 ± 0.3 vs. 4.4 ± 0.2), (amplitude: 12 ± 1.1 vs. 10.8 ± 1.1 ng/ml)] did not differ between groups (f1/f1 vs. f1/d3 plus d3/d3). In addition, we did not observe any significant differences in serum IGF-I SDS (–0.49 ± 0.26 vs. –0.40 ± 0.35) or IGFBP-3 SDS (–1.21 ± 0.24 vs. –0.89 ± 0.21) nor in insulin sensitivity (WIBSI: 12 ± 1.2 vs. 10.8 ± 1.1) in LBW children with full length GHR compared to children carrying at least one GHRd3 allele. The distribution of the f1/f1 allelic variant and fi/d3 or d3/d3 was similar in the LBW children with or without catch-up growth. These results suggest that the GHR allelic variant does not play a significant role in the regulation of GH-IGF-I/BP3 axis or in insulin sensitivity in prepubertal LBW children.
Generation of Allergen-Enriched Protein Fractions of Hevea brasiliensis Latex for in vitro and in vivo Diagnosis
Authors: Wagner S. , Bublin M. , Hafner C. , Kopp T. , Allwardt D. , Seifert U. , Arif S.A. , Scheiner O. , Breiteneder H.
Published: March 2007

Background: The latex of Hevea brasiliensis trees contains a complex proteome that includes a range of allergenic proteins. Current latex extracts that are used for the diagnosis of latex allergy still lack important allergens. We aimed to devise a production process for an improved reagent that would ideally contain the complete latex allergome. Methods: Latex C-serum was fractionated by ammonium sulfate precipitation, and B- and C-serum proteins were then separated by anion exchange chromatography. Proteins eluting within defined salt concentration ranges were pooled into six final fractions. Fractions were evaluated by two-dimensional electrophoresis and subsequent IgE immunoblot for their spectrum of allergens. The presence of the most important latex allergens in the fractions was checked by Western blot analyses. Each fraction was further evaluated by skin prick test (SPT). Results: Reproducibility of the preparation method was demonstrated with two batches of latex. Comparison of latex B- and C-serum to the six fractions showed a remarkable increase in the number of detectable allergens in the fractions. The presence of the latex allergens Hev b 1–8 and Hev b 13 in the fractions was demonstrated. In SPTs, the fractions produced wheal-and-flare reactions comparable to commercial latex extracts. Conclusions: This method provides reproducible latex protein fractions of high allergen content for the diagnosis of latex allergy.
Age-Related Difference in the Persistency of Allergic Airway Inflammation and Bronchial Hyperresponsiveness in a Murine Model of Asthma
Authors: Mayuzumi Hiroo , Ohki Yasushi , Tokuyama Kenichi , Sato Akira , Mizuno Takahisa , Arakawa Hirokazu , Mochizuki Hiroyuki , Morikawa Akihiro
Published: March 2007

Aim: Asthmatic children are more likely to outgrow their symptoms than adult patients. Thus, we wanted to know whether there were any age-related differences in the time course of the allergic airway inflammation. Methods: BALB/C mice at different ages (young: 3 days after birth, and mature: 8 weeks of age) were sensitized with ovalbumin (OVA). Subsequently, animals were challenged with aerosolized OVA during 1, 2, 4 or 8 consecutive weeks. Bronchial hyperresponsiveness (BHR), serum IgE levels, the degrees of inflammatory cell infiltration (ICI) and goblet cell metaplasia (GCM) in the airways, and the number of eosinophils and cytokine levels in bronchoalveolar lavage fluid (BALF) were examined. Results: At 1 week, airway inflammation and BHR occurred similarly between young and mature mice. However, BHR disappeared at 4 weeks in young, whereas it persisted even at 8 weeks in mature mice. GCM, ICI and eosinophilia in BALF attenuated with time, with more remarkable reduction in young mice. The BALF IL-4 level was high during the first 2 weeks in both groups, while the IL-2 level was significantly increased at 2 weeks solely in young mice. Conclusion: Different time courses in airway inflammation and in BHR may relate to the different prognoses between childhood and adult asthma. The understanding of the mechanisms underlying this age-related differences may be helpful to induce remission in asthmatic patients.
Unexpected Phenotype of STAT6 Heterozygous Mice Implies Distinct STAT6 Dosage Requirements for Different IL-4 Functions
Authors: Bürgis Susanne , Gessner André
Published: March 2007

Background: STAT6 is an important transcription factor in interleukin-4 (IL-4) signaling, a key cytokine in atopic diseases and allergic asthma. STAT6 gene-targeted mice are unable to develop IgE and T helper 2 cell (Th2) responses in several models of allergic and infectious diseases. In experiments to further elucidate STAT6 functions in vivo, we unexpectedly observed severely impaired IL-4 functions in STAT6 heterozygous (STAT6+/–) mice which were further analyzed in this study. Methods: BALB/c mice, either wild-type (STAT6+/+), STAT6 heterozygous (STAT6+/–) or STAT6 deficient (STAT6–/–), were analyzed for their ability to mount an IL-4-induced IgE response in vitro and in vivo. Supernatants of stimulated B cells and sera of Leishmania major-infected mice were analyzed for IgE, IgG1 and IgG2a concentrations by ELISA. Transcripts accompanying IgE class switching were amplified by RT-PCR and the expression of CD23 and MHC class II molecules on B cells was assessed by FACS analysis. Results: B cells from STAT6+/– mice were unable to secrete IgE in vitro and in vivo and transcripts accompanying IgE class switching were drastically reduced, whereas IL-4-induced upregulation of MHC class II was unimpaired and CD23 expression levels were only slightly affected. Additionally, STAT6+/– mice were equally resistant to infection with L. major as STAT6-deficient (STAT6–/–) mice, due to a defect in mounting a Th2-dominated immune response. Conclusion: Different STAT6-dependent IL-4 functions require different thresholds of activated STAT6 molecules.
The Impact of Computer and Imaging Technology on Stereotactic Surgery
Authors: Kall Bruce A.
Published: March 2007

Computers, particularly medical imaging techniques, have created a renaissance in stereotactic surgery. Human stereotaxis was primarily developed and performed beginning in the 1940s for functional disorders. Interest waned in the 1960s following the introduction of L-dopa until computer-based three-dimensionally precise tomographic modalities (specifically computed tomography) were introduced beginning in the mid-1970s as a routine diagnostic aid. New image-compatible hardware and instrumentation were introduced along with techniques and associated software for relating points and volumes appearing on these diagnostic images into stereotactic space. This paper reviews the computer and imaging technology that has led to this renaissance and discusses some of the important features of a computer-interactive stereotactic system.
Stereotactic Surgical Planning with Magnetic Resonance Imaging, Digital Subtraction Angiography and Computed Tomography
Authors: Peters T.M. , Clark J. , Pike B. , Drangova M. , Olivier A.
Published: March 2007

Over the past 2 years at the Montreal Neurological Institute and Hospital, we have evolved an integrated environment for the planning of stereotactic procedures, based on images from magnetic resonance imaging, digital subtraction angiography and computed tomography modalities. These procedures rely on fiducial marker sets which are attached to our ''OBT'' stereotactic frame, and which may be recognized in the images. The software package is modular and operates in both minicomputer (PDP-11 and VAX) and IBM personal computer environments. In addition to routine tasks for stereotactic planning, the package also supports dosimetry planning for stereotactic radio-surgery.
Creation of a Three-Dimensional Atlas by Interpolation from Schaltenbrand-Bailey's Atlas
Authors: Yoshida Masafumi
Published: March 2007

A 0.5-mm step atlas was interpolated from Schaltenbrand-Bailey''s atlas. By serial display of the atlas with the desired rotation on a three-dimensional axis, a three-dimensional atlas was created. The newly created atlas can be used for computerprocessed stereotactic data display. Any three-dimensionally located point can be displayed within 0.25 mm distance from the point, and spatial understanding of anatomical structures and stereotactic data is facilitated by the three-dimensional display.
Three-Dimensional Reconstruction of Neuroradiological Data within a Stereotactic Frame of Reference for Surgery of Visible Targets
Authors: Giorgi C. , Ongania E. , Franzini A. , Broggi G.
Published: March 2007

Three-dimensional information obtained with neuroradiological exams performed under stereotactic conditions is displayed on a surgical console within the graphic reconstruction of the geometry of stereotactic frames. Planning of convenient probe trajectories can be carried out taking into account all data derived from different diagnostic techniques.
Angiographic Localizer for the BRW Stereotactic System
Authors: Vandermeulen D.V. , Suetens P. , Gybels J. , Oosterlinck A. , Cosman E.R. , Wells Jr. T.H.
Published: March 2007

Preliminary experience with a newly constructed angiographic localizer system for use in stereotactic neurosurgery is reported. This localizer ring, mounted on the BRW head ring, allows for the transformation of target points with known stereotactic coordinates (e.g., visible on computerized tomography scans) onto angiograms, as well as the determination of stereotactic coordinates of a set of points (e.g., arteriovenous malformations) indicated on at least two angiograms.
Combined Use of Digital Subtraction Angiography and MRI for Radiosurgery and Stereoencephalography
Authors: Olivier A. , de Lotbinière A. , Peters T. , Pike B. , Ethier R. , Melanson D. , Bertrand G. , Podgorsak E.
Published: March 2007

The authors report their experience with the combined use of digital subtraction angiography (DSA) and magnetic resonance imaging (MRI) for the stereotactic placement of intracerebral electrodes in epilepsy and for the radiosurgical treatment of otherwise inoperable arteriovenous malformations of the brain. Both imaging techniques, when used in conjunction, have been found most useful and complementary. For deep electrode placement, they permit optimal visualization of the cerebral structures to be reached by the electrode array while allowing the avoidance of vessels in the vicinity. For radiosurgery of arteriovenous malformations, DSA provides optimal visualization of the feeders and of the malformation itself, while the MRI reveals the cerebral structures to be spared by the photon beam of the linear accelerator. A discussion of their respective roles is presented, with the specific question as to whether MRI alone could be used for both procedures.
Combined Use of a New Target-Centered Are System with the BRW Floor Stand and Phantom Base for a Wider Range of Approaches and Applications in Stereotaxy of the Head and Neck
Authors: Cosman Eric R. , Wells Jr. Trent H.
Published: March 2007

A unique target-centered arc system has been developed which combines the azimuth and declination angle approach concept of the standard BRW are with the anteroposterior, lateral and vertical movements of the earlier Todd-Wells Guide for maximal versatility of image-guided stereotaxy. The arc system mounts on the BRW floor stand and provides completely unobstructed approaches to the upper hemisphere, base of the skull, posterior fossa or cervical region. It is ideally adapted for implant ar-rays and laser surgery. A new transferable phantom pointer affords target confirmation using the BRW phantom base.
Experience with the Pelorus Stereotactic System
Authors: Carol M. , Smith D. , Love L. , Schumann B. , Cahill D.
Published: March 2007

The Pelorus stereotactic system, by its unique approach, alleviates the need for the traditional head frame and computer-generated coordinates which are common to most other systems. Despite its simplicity, it sacrifices nothing in terms of the range of problems for which it can be used to diagnose and treat. In fact, its unencumbered design may make it more appropriate for advanced procedures than conventional systems.
MRI Contribution to the Stereotactic Management of Cerebral Tumours
Authors: Mercier C. , Le Bas J.F. , Benabid A.L. , Pasquier B.
Published: March 2007

Of 67 patients with cerebral tumours studied by MRI, 60 underwent stereotactic biopsy for histological diagnosis. The data from MRI were compared with those obtained from the CT scan with regard to the pathological diagnosis. The tumoural nature and extent of a lesion were better revealed by MRI. The single or multiple localization of the process was also seen better by MRI. Moreover, the sagittal-piane views shown by MRI provide much more accurate target placement and probe guiding for an orthogonal stereotactic approach. Finally, a post-biopsy MRI can show the biopsy site in relation to the tumour better.
Stereotactic Biopsy for Deep-Seated Intracerebral Lesions
Authors: Matsumura Masaru , Kawashima Yasuhiro , Shibazaki Tohru , Ohye Chihiro
Published: March 2007

In 16 cases of stereotactic deep brain biopsy, a correlative study was made by computer tomography, positron emission tomography, and electrophysiological depth recording. This multimodal study is shown to be of great value in stereotactic biopsy of deep-seated cerebral lesions.
Technique of Stereotactic Biopsy of Two Cranial Targets Employing Spherical Coordinates to Define a Single Trajectory
Authors: Kopitnik Jr. Thomas A. , Kaufman Howard H. , Haid Regis W. , Marano Gary D. , Nugent G. Robert
Published: March 2007

A ''spherical coordinate system'' has been developed to allow either stereotactic biopsy of two intracranial lesions using a single predetermined trajectory or biopsy of a single lesion through an existing burr hole. By means of the Gildenberg technique, the CT coordinates of the targets (or target and burr hole) are obtained. These are employed in three simple trigonometric equations to give three coordinates – two angles for the probe carrier (Θ and α) and the radius (T) of a sphere, defined by one target as the center and the other target on the surface. These can be utilized in the Todd-Wells stereotactic frame. This system was evaluated using hollow skulls and crossed 30-gauge wire for phantom targets. The system was tried on ten different target cmbinations, and eight successful trajectories were obtained to within 3 mm. Two target combinations were inaccessible because of technical limitations of the Todd-Wells frame. This ''spherical coordinate system'' can decrease the time to localize multiple targets as well as minimize the number of passes.
Stereotaxy and Thalamic Masses
Authors: Frank F. , Fabrizi A.P. , Gaist G. , Frank-Ricci R. , Piazzi M. , Spagnolli F.
Published: March 2007

Thalamic masses are generally considered inoperable; little is known of the precise nature of these lesions. Stereotactic biopsy was performed in 44 patients, with no mortality and low morbidity (only 1 case of transitory hemiparesis). The stereotactic biopsy (minimum 5 specimens taken along the major axis of the lesion) showed that the majority of the young patients (<40 years) had low-grade glial neoplasms (grade I–II astrocytomas or oligodendrogliomas), while in older patients highly malignant tumors prevailed. Beside the neoplasms in the children and adults, we found granulomas, abscesses, infarcts, hemorrhages and glioses. Present neuroradiological methods cannot establish a final correct diagnosis in thalamic lesions, so stereotactic biopsy is recommended. A follow-up of 1–6 years is presented for 7 patients who underwent stereotactic 125I brachy-therapy.
Linear Accelerator Radiosurgery of Arteriovenous Malformations
Authors: Colombo Federico , Benedetti Antonio , Casentinia Leopoldo , Zanusso Mariano , Pozza Franco
Published: March 2007

Forty-five patients affected by cerebral arteriovenous malformations not suitable to open surgery have been treated by a radiosurgical technique employing a linear accelerator. One-year follow-up angiography is available for 10 cases. Therapeutic effect of focalized irradiation is presented.
Physical Aspects of Dynamic Stereotactic Radiosurgery
Authors: Podgorsak Ervin B. , Olivier André , Pla Marina , Hazel Joseph , de Lotbinière Alain , Pike Bruce
Published: March 2007

Dynamic stereotactic radiosurgery is a radiosurgical technique based on a medium-energy isocentric linear accelerator and a stereotactic frame. The technique uses concurrent and continuous rotations of both the gantry (300°, from 30 to 330°) and the couch (150°, from 75 to –75°). It gives a uniform dose (±5%) within the target volume and dose fall-offs outside the target volume comparable to those obtained from presently known radiosurgical techniques.
Single-Scan Stereotactic Tumor Biopsy and Brachytherapy
Authors: Goodman J.H. , Davis J.R. , Gabauer R.A. , Kanellitsas C.
Published: March 2007

Stereotactic tumor biopsy and brachytherapy catheter implantation can be accomplished with targets derived from computed axial tomography and magnetic resonance scans. Computer manipulation of image data allows both diagnostic and therapeutic procedures to be carried out from a single set of scan slices. This eliminates the need for repeat scanning as part of the surgical procedure. Microcomputer technology is sufficiently advanced to handle the images and graphics necessary for stereotactic neurosurgery. A system based on the IBM PC/ATdesigned for this purpose uses readily available graphics software and custom-designed imaging programs. Direct loading of computed axial or magnetic resonance scan images from magnetic tape can be accomplished. Determination of points, contours and volumes in three-dimensional space allows intraoperative alignment of image data and patient landmarks within the stereotactic head frame using pattern recognition overlays. Three-axis scaling for magnification correction along with rotational and linear data transformations provide the basis for singlescan stereotaxis. Interactive computer graphics integrate image, patient and frame coordinates for target determination. This method eliminates the need to design and fabricate nonmagnetic or radiolucent scanner-compatible devices.
Choice of Radioisotope in Stereotactic Interstitial Radiotherapy of Small Brain Tumors
Authors: Jani S.K. , Hitchon P.W. , VanGilder J.C. , Pennington E.C. , Hussey D.H.
Published: March 2007

In stereotactic interstitial radiotherapy, small radioactive sources are placed within the brain tumor to deliver locally high radiation doses. The choice of the radioisotope depends upon the dose distribution around the isotope, energy of the emitted radiation, relative biological effectiveness, and finally, the cost and availability of the isotope. We have analyzed 198gold,125iodine and 192iridium in terms of these four factors. Our results have shown that 125I is superior to the other two isotopes due to its soft X-rays and dosimetric as well as radiobiological properties. Unfortunately, it is the most expensive of these radioisotopes, and can be difficult to obtain in specific activities.
Observations and Analysis of Results in 131 Cases of Spasmodic Torticollis after Selective Denervation
Authors: Bertrand C. , Molina-Negro P. , Bouvier G. , Gorczyca W.
Published: March 2007

In 131 patients treated exclusively by selective denervation during the past 10 years, all or almost all the abnormal movements of spasmodic toricollis were suppressed in 115 (88%) while preserving posture and mobility. This approach was also used in certain forms of adult-onset dystonia. An appreciable amount of abnormal movements remained in the other patients, either due to residual innervation or because of limitation of denervation necessary to preserve normal movements (laterocollis) or neck stability (retrocollis). A medio-lateral approach to the posterior cervical region in the sitting position using stimulation under light anaesthesia is recommended.
Long-Term Follow-Up Study of Nucleus Ventralis Intermedius and Ventrolateralis Thalamotomy using a Microelectrode Technique in Parkinsonism
Authors: Narabayashi H. , Maeda T. , Yokochi F.
Published: March 2007

Long-term observation over 3–8 postoperative years of cases of Parkinson disease operated by stereotactic thalamotomy using a microelectrode recording technique is reported. The procedure is specifically useful in the following four groups: (1) tremor-dominant cases, (2) hemiparkinsonism, (3) cases with marked asymmetry in motor symptoms and (4) juvenile parkinsonism presenting levodopa-induced dyskinesia.
Automatic Calculation of Epileptogenic Focus Location Within the Brain
Authors: Barcia-Salorio J.L. , Barcia J.A. , Ciudad J. , Such Y.
Published: March 2007

The authors propose a hypothesis about the mathematical relationship between the position and intensity of epileptogenic discharge and the potential recorded from an electrocorticographic electrode. A computer program is used to solve the equation and to determine a small area of maximal probability for the focus to be found.
Corpus Callosum Section for Patients with Intractable Epilepsy
Authors: Garcia-Flores Eduardo
Published: March 2007

Microsurgical techniques of callosotomy were effective in relieving medically intractable epilepsy in 14 of 16 patients. Intra-arterial digital angiography has been used preoperatively to assess drainage of the veins of the frontal lobe. MRI is useful in verifying the postoperative extent of corpus callosum section. Patients with bilateral frontal lesions and unilateral destructive lesions responded to callosotomy. None of the patients had an increase in seizures after the procedure.
Thalamic Microelectrode Recording and Microstimulation in Central and Deafferentation Pain
Authors: Tasker R.R. , Gorecki J. , Lenz F.A. , Hirayama T. , Dostrovsky J.O.
Published: March 2007

Microelectrode recording and microstimulation (in 1 case macrostimula-tion) were used to localize stereotactic targets in 8 patients with central and deafferentation pain and 1 ‘deafferented control’ patient without pain. Off-line study revealed two features commonly proposed as potential physiological factors for such pain, but they were present in both pain and control patients - somatotopographic reorganization and the presence of bursting cells. In all patients in whom stimulation induced pain referred to deafferented parts of the contralateral body, hyperpathia or allodynia were present instead of normal paraesthetic, sensorimotor or t her mal responses.
Chronic Pain Syndromes
Authors: Andy Orlando J.
Published: March 2007

Brainstem-scalp discharge propagation was evaluated in 20 patients with chronic pain, of which 10 were ranked according to the frequency of involved systems making up the chronic pain syndrome. It is concluded that brainstem discharges alone were sufficient to generate the chronic pain syndrome.
Double Vision Corrected by Thalamic Stimulation
Authors: Andy Orlando J. , Andy Maria L.
Published: March 2007

Three patients with chronic headaches also complained of double vision. Additional findings were bilateral eye blinking in 1 patient and ipsilateral eye roll in another which became synchronous with heart rate during perturbation of the mesothalamic area. Mesothalamic stimulation attenuated the discharges and the above signs and symptoms. Mechanisms underlying these ocular disturbances are discussed.
Electrophysiologic Studies in Selective Dorsal Rhizotomy for Spasticity in Children with Cerebral Palsy
Authors: Cahan Leslie D. , Kundi M.S. , McPherson David , Starr Arnold , Peacock Warwick
Published: March 2007

A group of 20 children with spastic cerebral palsy underwent selective dorsal rhizotomy for alleviation of spasticity. Pre- and postoperatively, cortical somatosensory evoked responses (cSSEP), H reflex and F wave studies were done. Clinically there was dramatic reduction of tone without noticeable sensory loss. The electrophysiologic studies showed several findings: (1) many children have abnormal cSSEP preoperatively; (2) surgery seldom leads to a loss of cSSEP; (3) in many patients, there is a note-worthy improvement in the cSSEP wave form; (4) some children have electrophysiologic evidence of spinal cord dysfunction preoperatively and (5) Hmax/Mmax ratio decreases after surgery confïrming decrease in tone.
CT-Controlled Stereotactic Aspiration in Hypertensive Brain Hemorrhage
Authors: Hondo Hideki , Matsumoto Keizo , Tomida Keisuke , Shichijo Fumio
Published: March 2007

CT-guided stereotactic aspiration surgery for the evacuation of hypertensive brain hemorrhage (HBH) has been introduced recently. From December, 1980, to April, 1986, we used aspiration surgery in 375 cases of HBH. The 6-month postoperative outcome of aspiration surgery for acute basal-ganglionic hemorrhage was compared with that after conventional surgery of all Japan and those after conservative treatment. In basal-ganglionic hemorrhage, aspiration surgery led to a favorable clinical experience and outcome, providing the possibility of a new avenue of surgical treatment of HBH.
Combined (Thalamotomy and Stimulation) Stereotactic Surgery of the VIM Thalamic Nucleus for Bilateral Parkinson Disease
Authors: Benabid A.L. , Pollak P. , Louveau A. , Henry S. , de Rougemont J.
Published: March 2007

Stereotactic thalamotomy of the thalamic nucleus ventralis intermedius (VIM) is routinely used for movement disorders. During this procedure, it has been observed that high-frequency (100 Hz) stimulation of VIM was able to stop the extrapyramidal tremor. In patients with bilateral tremor of extrapyramidal origin, who were resistant to drug therapy, the therapeutic protocol associated (1) a radiofrequency VIM thalamotomy for the most disabled side, and (2) a continuous VIM stimulation for the other side using stereotactically implanted electrodes, connected to subcutaneous stimulators. VIM thalamotomy relieved the tremor in all operated cases. Side effects were mild and regressive, VIM stimulation strongly decreasedthe tremor but failed to suppress it as completely as thalamotomy did. This was due in part to the fact that programmable stimulator frequency rate is limited to 130 Hz, while it appeared that the optimal stimulation frequency was 200 Hz. This therapeutic protocol appears to be of interest for patients with bilateralextrapyramidal movement disorders.
Activation of Transient Receptor Potential Vanilloid Type-1 Channel Prevents Adipogenesis and Obesity
Authors: Zhang Li Li , Yan Liu Dao , Ma Li Qun , Luo Zhi Dan , Cao Ting Bing , Zhong Jian , Yan Zhen Cheng , Wang Li Juan , Zhao Zhi Gang , Zhu Shan Jun , Schrader Mark , Thilo Florian , Zhu Zhi Ming , Tepel Martin
Published: March 2007

We tested the hypothesis that activation of transient receptor potential vanilloid type-1 (TRPV1) by capsaicin prevents adipogenesis. TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans were detected by immunoblotting and quantitative real-time RT-PCR. The effect of TRPV1 on cytosolic calcium was determined fluorometrically in 3T3-L1-preadipocytes and in human visceral fat tissue. Adipogenesis in stimulated 3T3-L1-preadipocytes was determined by oil red O-staining of intracellular lipid droplets, triglyceride levels, expression of peroxisome proliferator-activated receptor-γ, and expression of fatty acid synthase. Long-term feeding experiments were undertaken in wild-type mice and TRPV1 knockout mice.

We detected TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans. In vitro, the TRPV1 agonist capsaicin dose-dependently induced calcium influx and prevented the adipogenesis in stimulated 3T3-L1-preadipocytes. RNA interference knockdown of TRPV1 in 3T3-L1-preadipocytes attenuated capsaicin-induced calcium influx, and adipogenesis in stimulated 3T3-L1-preadipocytes was no longer prevented. During regular adipogenesis TRPV1 channels were downregulated which was accompanied by a significant and time-dependent reduction of calcium influx. Compared with lean counterparts in visceral adipose tissue from obese db/db and ob/ob mice, and from obese human male subjects we observed a reduced TRVP1 expression. The reduced TRPV1 expression in visceral adipose tissue from obese humans was accompanied by reduced capsaicin-induced calcium influx. The oral administration of capsaicin for 120 days prevented obesity in male wild type mice but not in TRPV1 knockout mice assigned to high fat diet. We conclude that the activation of TRPV1 channels by capsaicin prevented adipogenesis and obesity.
Early Exercise Training Normalizes Myofilament Function and Attenuates Left Ventricular Pump Dysfunction in Mice With a Large Myocardial Infarction
Authors: de Waard Monique C. , van der Velden Jolanda , Bito Virginie , Ozdemir Semir , Biesmans Liesbeth , Boontje Nicky M. , Dekkers Dick H.W. , Schoonderwoerd Kees , Schuurbiers Hans C.H. , Crom Rini de , Stienen Ger J.M. , Sipido Karin R. , Lamers Jos M.J. , Duncker Dirk J.
Published: March 2007

The extent and mechanism of the cardiac benefit of early exercise training following myocardial infarction (MI) is incompletely understood, but may involve blunting of abnormalities in Ca
2+
-handling and myofilament function. Consequently, we investigated the effects of 8-weeks of voluntary exercise, started early after a large MI, on left ventricular (LV) remodeling and dysfunction in the mouse. Exercise had no effect on survival, MI size or LV dimensions, but improved LV fractional shortening from 8±1 to 12±1%, and LVdP/dt
P30
from 5295±207 to 5794±207 mm Hg/s (both
P
<0.05), and reduced pulmonary congestion. These global effects of exercise were associated with normalization of the MI-induced increase in myofilament Ca
2+
-sensitivity (ΔpCa
50
=0.037). This effect of exercise was PKA-mediated and likely because of improved β
1
-adrenergic signaling, as suggested by the increased β
1
-adrenoceptor protein (48%) and cAMP levels (36%; all
P
<0.05). Exercise prevented the MI-induced decreased maximum force generating capacity of skinned cardiomyocytes (F
max
increased from 14.3±0.7 to 18.3±0.8 kN/m
2
P
<0.05), which was associated with enhanced shortening of unloaded intact cardiomyocytes (from 4.1±0.3 to 7.0±0.6%;
P
<0.05). Furthermore, exercise reduced diastolic Ca
2+
-concentrations (by ∼30%,
P
<0.05) despite the unchanged SERCA2a and PLB expression and PLB phosphorylation status. Importantly, exercise had no effect on Ca
2+
-transient amplitude, indicating that the improved LV and cardiomyocyte shortening were principally because of improved myofilament function. In conclusion, early exercise in mice after a large MI has no effect on LV remodeling, but attenuates global LV dysfunction. The latter can be explained by the exercise-induced improvement of myofilament function.
Transient Exposure to Hydrogen Peroxide Causes an Increase in Mitochondria-Derived Superoxide As a Result of Sustained Alteration in L-Type Ca
2+
Channel Function in the Absence of Apoptosis in Ventricular Myocytes
Authors: Viola Helena M. , Arthur Peter G. , Hool Livia C.
Published: March 2007

We sought to understand the effect of a transient exposure of cardiac myocytes to H
2
O
2
at a concentration that did not induce apoptosis. Myocytes were exposed to 30 μmol/L H
2
O
2
for 5 minutes followed by 10 U/mL catalase for 5 minutes to degrade the H
2
O
2
. Cellular superoxide was measured using dihydroethidium. Transient exposure to H
2
O
2
caused a 66.4% increase in dihydroethidium signal compared with controls exposed to only catalase, without activation of caspase 3 or evidence of necrosis. The increase in dihydroethidium signal was attenuated by the mitochondrial inhibitors myxothiazol or carbonyl cyanide
p
-(trifluoromethoxy)phenyl-hydrazone and when calcium uptake by the mitochondria was inhibited with Ru360. We investigated the L-type Ca
2+
channel (
I
Ca-L
) as a source of calcium influx. Nisoldipine, an inhibitor of
I
Ca-L
, attenuated the increase in superoxide. Basal channel activity increased from 5.4 to 8.9 pA/pF. Diastolic calcium was significantly increased in quiescent and contracting myocytes after H
2
O
2
. The response of
I
Ca-L
to β-adrenergic receptor stimulation was used as a functional reporter because decreasing intracellular H
2
O
2
alters the sensitivity of
I
Ca-L
to isoproterenol. H
2
O
2
increased the
K
0.5
required for activation of
I
Ca-L
by isoproterenol from 5.8 to 27.8 nmol/L. This effect and the increase in basal current density persisted for several hours after H
2
O
2
. We propose that extracellular H
2
O
2
is associated with an increase in superoxide from the mitochondria caused by an increase in Ca
2+
influx from
I
Ca-L
. The effect persists because a positive feedback exists among increased basal channel activity, elevated intracellular calcium, and superoxide production by the mitochondria.
Upregulation of Macrophage Endothelial Lipase by Toll-Like Receptors 4 and 3 Modulates Macrophage Interleukin-10 and -12 Production
Authors: Wang Xun , Jin Weijun , Rader Daniel J.
Published: March 2007

Limited data suggest that endothelial lipase (EL) is synthesized not only by endothelial cells but also by macrophages. Previous studies showed that proinflammatory cytokines upregulate EL in endothelial cells, but there are very few data regarding EL expression, regulation, and functional consequences in macrophages. In the present study, RAW cells and mouse peritoneal macrophages were treated with Toll-like receptor (TLR) ligands and EL expression and its consequences were assessed. We demonstrate that lipopolysaccharide, a TLR4 ligand; and polyinosinic:polycytidylic acid (poly I:C), a TLR3 ligand; but not lipoteichoic acid, a TLR2 ligand, upregulate macrophage EL expression both ex vivo and in vivo. In contrast, macrophage lipoprotein lipase expression is significantly repressed by lipopolysaccharide or poly I:C. Using C3HJ and TLR3 knockout mice, we further show that upregulation of macrophage EL expression by lipopolysaccharide or poly I:C is TLR4 or TLR3 dependent, respectively. Furthermore, we demonstrate that lipopolysaccharide induced interleukin (IL)-10 production was significantly reduced, whereas IL-12 production is significantly increased in J744 macrophages and mouse peritoneal macrophages overexpressing human EL. Conversely, significantly increased IL-10 and significantly decreased IL-12 expression were observed in mouse peritoneal macrophages isolated from EL knockout mice. Finally we show that the catalytic activity is required for EL to modulate the balance of macrophage IL-10 and IL-12 production. These results suggest that macrophage EL may play important roles in modulating the macrophage inflammatory response through local hydrolysis of HDL.
cAMP Signaling in Leukocyte Transendothelial Migration
Authors: Lorenowicz Magdalena J. , Fernandez-Borja Mar , Hordijk Peter L.
Published: March 2007

The migration of leukocytes across the vascular endothelium is crucial for immunosurveillance as well as for inflammatory responses. Uncontrolled leukocyte transendothelial migration results in pathologies such as asthma, rheumatoid arthritis, and atherosclerosis. The molecular mechanisms that regulate leukocyte transendothelial migration involve signaling downstream of intracellular messengers such as cAMP, calcium, phosphoinositol lipids, or reactive oxygen species. Among these, cAMP is particularly intriguing because it is generated in both leukocytes and endothelial cells and regulates leukocyte chemotaxis as well as endothelial barrier function. In addition, physiological stimuli that induce cAMP production generate both pro- and antiinflammatory signals, underscoring the complexity of cAMP-driven signaling. This review discusses our current knowledge of the control of leukocyte transendothelial migration by two main cAMP effectors: protein kinase A and the Rap exchange factor Epac (
E
xchange
p
rotein directly
a
ctivated by
c
AMP).