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1.
Clin Neurophysiol ; 146: 49-54, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36535091

ABSTRACT

OBJECTIVE: Distinguishing normal, neuropathic and myopathic electromyography (EMG) traces can be challenging. We aimed to create an automated time series classification algorithm. METHODS: EMGs of healthy controls (HC, n = 25), patients with amyotrophic lateral sclerosis (ALS, n = 20) and inclusion body myositis (IBM, n = 20), were retrospectively selected based on longitudinal clinical follow-up data (ALS and HC) or muscle biopsy (IBM). A machine learning pipeline was applied based on 5-second EMG fragments of each muscle. Diagnostic yield expressed as area under the curve (AUC) of a receiver-operator characteristics curve, accuracy, sensitivity, and specificity were determined per muscle (muscle-level) and per patient (patient-level). RESULTS: Diagnostic yield of the classification ALS vs. HC was: AUC 0.834 ± 0.014 at muscle-level and 0.856 ± 0.009 at patient-level. For the classification HC vs. IBM, AUC was 0.744 ± 0.043 at muscle-level and 0.735 ± 0.029 at patient-level. For the classification ALS vs. IBM, AUC was 0.569 ± 0.024 at muscle-level and 0.689 ± 0.035 at patient-level. CONCLUSIONS: An automated time series classification algorithm can distinguish EMGs from healthy individuals from those of patients with ALS with a high diagnostic yield. Using longer EMG fragments with different levels of muscle activation may improve performance. SIGNIFICANCE: In the future, machine learning algorithms may help improve the diagnostic accuracy of EMG examinations.


Subject(s)
Amyotrophic Lateral Sclerosis , Myositis, Inclusion Body , Peripheral Nervous System Diseases , Humans , Electromyography , Retrospective Studies , Amyotrophic Lateral Sclerosis/diagnosis , Machine Learning , Muscle, Skeletal
2.
Clin Neurophysiol ; 132(5): 1041-1048, 2021 05.
Article in English | MEDLINE | ID: mdl-33743299

ABSTRACT

OBJECTIVE: A downside of Deep Brain Stimulation (DBS) for Parkinson's Disease (PD) is that cognitive function may deteriorate postoperatively. Electroencephalography (EEG) was explored as biomarker of cognition using a Machine Learning (ML) pipeline. METHODS: A fully automated ML pipeline was applied to 112 PD patients, taking EEG time-series as input and predicted class-labels as output. The most extreme cognitive scores were selected for class differentiation, i.e. best vs. worst cognitive performance (n = 20 per group). 16,674 features were extracted per patient; feature-selection was performed using a Boruta algorithm. A random forest classifier was modelled; 10-fold cross-validation with Bayesian optimization was performed to ensure generalizability. The predicted class-probabilities of the entire cohort were compared to actual cognitive performance. RESULTS: Both groups were differentiated with a mean accuracy of 0.92; using only occipital peak frequency yielded an accuracy of 0.67. Class-probabilities and actual cognitive performance were negatively linearly correlated (ß = -0.23 (95% confidence interval (-0.29, -0.18))). CONCLUSIONS: Particularly high accuracies were achieved using a compound of automatically extracted EEG biomarkers to classify PD patients according to cognition, rather than a single spectral EEG feature. SIGNIFICANCE: Automated EEG assessment may have utility for cognitive profiling of PD patients during the DBS screening.


Subject(s)
Cognitive Dysfunction/diagnosis , Deep Brain Stimulation/adverse effects , Electroencephalography/methods , Machine Learning , Parkinson Disease/therapy , Aged , Cognition , Cognitive Dysfunction/etiology , Deep Brain Stimulation/methods , Electroencephalography/standards , Female , Humans , Male , Middle Aged , Predictive Value of Tests
3.
Phys Rev Lett ; 124(6): 062501, 2020 Feb 14.
Article in English | MEDLINE | ID: mdl-32109090

ABSTRACT

The low-lying energy spectrum of the extremely neutron-deficient self-conjugate (N=Z) nuclide _{44}^{88}Ru_{44} has been measured using the combination of the Advanced Gamma Tracking Array (AGATA) spectrometer, the NEDA and Neutron Wall neutron detector arrays, and the DIAMANT charged particle detector array. Excited states in ^{88}Ru were populated via the ^{54}Fe(^{36}Ar,2nγ)^{88}Ru^{*} fusion-evaporation reaction at the Grand Accélérateur National d'Ions Lourds (GANIL) accelerator complex. The observed γ-ray cascade is assigned to ^{88}Ru using clean prompt γ-γ-2-neutron coincidences in anticoincidence with the detection of charged particles, confirming and extending the previously assigned sequence of low-lying excited states. It is consistent with a moderately deformed rotating system exhibiting a band crossing at a rotational frequency that is significantly higher than standard theoretical predictions with isovector pairing, as well as observations in neighboring N>Z nuclides. The direct observation of such a "delayed" rotational alignment in a deformed N=Z nucleus is in agreement with theoretical predictions related to the presence of strong isoscalar neutron-proton pair correlations.

4.
Nanotechnology ; 26(10): 105706, 2015 Mar 13.
Article in English | MEDLINE | ID: mdl-25694166

ABSTRACT

Acid spun carbon nanotube (CNT) fibers were investigated for their field emission properties and performance was determined to be dependent on fiber morphology. The fibers were fabricated by wet-spinning of pre-made CNTs. Fiber morphology was controlled by a fabrication method and processing conditions, as well as purity, size, and type of the CNT starting material. The internal fiber structure consisted of CNT fibrils held together by van der Waals forces. Alignment and packing density of the CNTs affects the fiber's electrical and thermal conductivity. Fibers with similar diameters and differing morphology were compared, and those composed of the most densely packed and well aligned CNTs were the best field emitters as exhibited by a lower turn-on voltage and a larger field enhancement factor. Fibers with higher electrical and thermal conductivity demonstrated higher maximum current before failure and longer lifetimes. A stable emission current at 3 mA was obtained for 10 h at a field strength of <1 V µm(-1). This stable high current operation makes these CNT fibers excellent candidates for use as low voltage electron sources for vacuum electronic devices.

5.
Water Sci Technol ; 66(5): 1088-95, 2012.
Article in English | MEDLINE | ID: mdl-22797239

ABSTRACT

The optimization of full-scale biogas plant operation is of great importance to make biomass a competitive source of renewable energy. The implementation of innovative control and optimization algorithms, such as Nonlinear Model Predictive Control, requires an online estimation of operating states of biogas plants. This state estimation allows for optimal control and operating decisions according to the actual state of a plant. In this paper such a state estimator is developed using a calibrated simulation model of a full-scale biogas plant, which is based on the Anaerobic Digestion Model No.1. The use of advanced pattern recognition methods shows that model states can be predicted from basic online measurements such as biogas production, CH4 and CO2 content in the biogas, pH value and substrate feed volume of known substrates. The machine learning methods used are trained and evaluated using synthetic data created with the biogas plant model simulating over a wide range of possible plant operating regions. Results show that the operating state vector of the modelled anaerobic digestion process can be predicted with an overall accuracy of about 90%. This facilitates the application of state-based optimization and control algorithms on full-scale biogas plants and therefore fosters the production of eco-friendly energy from biomass.


Subject(s)
Bioreactors , Carbon Dioxide , Environmental Monitoring/methods , Methane , Algorithms , Anaerobiosis , Biofuels , Hydrogen-Ion Concentration , Models, Theoretical
6.
Q J Nucl Med Mol Imaging ; 56(6): 487-95, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23358400

ABSTRACT

Targeted alpha therapy (TAT) a promising treatment for small, residual, and micrometastatic diseases has questionable efficacy against malignant lesions larger than the α-particle range, and likely requires favorable intratumoral activity distribution. Here, we characterized and quantified the activity distribution of an alpha-particle emitter radiolabelled antibody within >100-µm micrometastases in a murine ovarian carcinoma model. Nude mice bearing ovarian micrometastases were injected intra-peritoneally with 211At-MX35 (total injected activity 6 MBq, specific activity 650 MBq/mg). Animals were sacrificed at several time points, and peritoneal samples were excised and prepared for alpha-camera imaging. Spatial and temporal activity distributions within micrometastases were derived and used for small-scale dosimetry. We observed two activity distribution patterns: uniform distribution and high stable uptake (>100% IA/g at all time points) in micrometastases with no visible stromal compartment, and radial distribution (high activity on the edge and poor uptake in the core) in tumor cell lobules surrounded by fibroblasts. Activity distributions over time were characterized by a peak (140% IA/g at 4 h) in the outer tumor layer and a sharp drop beyond a depth of 50 µm. Small-scale dosimetry was performed on a multi-cellular micrometastasis model, using time-integrated activities derived from the experimental data. With injected activity of 400 kBq, tumors exhibiting uniform activity distribution received <25 Gy (EUD=13 Gy), whereas tumors presenting radial activity distribution received mean absorbed doses of <8 Gy (EUD=5 Gy). These results provide new insight into important aspects of TAT, and may explain why micrometastases >100 µm might not be effectively treated by the examined regimen.


Subject(s)
Astatine/pharmacokinetics , Astatine/therapeutic use , Neoplasm Micrometastasis/radiotherapy , Ovarian Neoplasms/radiotherapy , Ovarian Neoplasms/secondary , Radiometry/methods , Radiotherapy Dosage , Alpha Particles/therapeutic use , Animals , Cell Line, Tumor , Female , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Micrometastasis/diagnostic imaging , Ovarian Neoplasms/metabolism , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Radiopharmaceuticals/therapeutic use , Treatment Outcome
7.
Phys Rev Lett ; 107(17): 173201, 2011 Oct 21.
Article in English | MEDLINE | ID: mdl-22107514

ABSTRACT

Atomic-field bremsstrahlung has been studied with a longitudinally polarized electron beam. The correlation between the initial orientation of the electron spin and the angle of photon polarization has been measured at the photon high energy tip region. In the time reversal this corresponds to a so-far unobserved phenomenon of production of longitudinally polarized electrons by photoionization of unpolarized atoms with linearly polarized photons. The results confirm the fully relativistic calculations for radiative recombination and suggest a new method for electron beam polarimetry.

8.
Clin Radiol ; 66(11): 1036-48, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21737069

ABSTRACT

AIM: To determine the diagnostic accuracy of ultrasound to detect partial and complete thickness rotator cuff tears based on all available clinical trials. MATERIALS AND METHODS: An electronic search of databases registering published and unpublished literature was conducted. All diagnostic accuracy studies that directly compared the accuracy of ultrasound (the index test) to either arthroscopic or open surgical findings (the reference test) for rotator cuff tear were included. The methodological quality of each included study was assessed using the QUADAS form. When appropriate, pooled sensitivity and specificity analysis was conducted, with an assessment of the summary receiver operating characteristic (ROC) curve for each analysis. RESULTS: Sixty-two studies assessing 6007 patients and 6066 shoulders were included. Ultrasonography had good sensitivity and specificity for the assessment of partial thickness (sensitivity 0.84; specificity 0.89), and full-thickness rotator cuff tears (sensitivity 0.96; specificity 0.93). However, the literature poorly described population characteristics, assessor blinding, and was based on limited sample sizes. The literature assessing transducer frequency was particularly small in size. CONCLUSION: Ultrasonography is an appropriate radiological technique for the assessment of rotator cuff tears with an acceptable sensitivity and specificity. The diagnostic test accuracy of ultrasound is superior for the detection of full-thickness compared to partial-thickness cuff tears. Further study assessing the effect of transducer frequency is warranted.


Subject(s)
Rotator Cuff Injuries , Rotator Cuff/diagnostic imaging , Tendon Injuries/diagnostic imaging , Female , Humans , Male , ROC Curve , Reproducibility of Results , Sensitivity and Specificity , Ultrasonography
9.
Nature ; 469(7328): 68-71, 2011 Jan 06.
Article in English | MEDLINE | ID: mdl-21179086

ABSTRACT

Shell structure and magic numbers in atomic nuclei were generally explained by pioneering work that introduced a strong spin-orbit interaction to the nuclear shell model potential. However, knowledge of nuclear forces and the mechanisms governing the structure of nuclei, in particular far from stability, is still incomplete. In nuclei with equal neutron and proton numbers (N = Z), enhanced correlations arise between neutrons and protons (two distinct types of fermions) that occupy orbitals with the same quantum numbers. Such correlations have been predicted to favour an unusual type of nuclear superfluidity, termed isoscalar neutron-proton pairing, in addition to normal isovector pairing. Despite many experimental efforts, these predictions have not been confirmed. Here we report the experimental observation of excited states in the N = Z = 46 nucleus (92)Pd. Gamma rays emitted following the (58)Ni((36)Ar,2n)(92)Pd fusion-evaporation reaction were identified using a combination of state-of-the-art high-resolution γ-ray, charged-particle and neutron detector systems. Our results reveal evidence for a spin-aligned, isoscalar neutron-proton coupling scheme, different from the previous prediction. We suggest that this coupling scheme replaces normal superfluidity (characterized by seniority coupling) in the ground and low-lying excited states of the heaviest N = Z nuclei. Such strong, isoscalar neutron-proton correlations would have a considerable impact on the nuclear level structure and possibly influence the dynamics of rapid proton capture in stellar nucleosynthesis.

10.
Nervenarzt ; 79(8): 918-20, 922-4, 926, 2008 Aug.
Article in German | MEDLINE | ID: mdl-18528673

ABSTRACT

BACKGROUND: The economic burden of stroke is considerable. While studies on the costs of acute stroke treatment have been undertaken in Germany, thorough analysis of direct and indirect long-term costs is lacking. PATIENTS AND METHODS: A hospital-based cohort of 151 consecutive patients with stroke or transient ischemic attacks (TIA) was followed up (medical examination and interview) at the end of the 4th year following the cerebrovascular event. Costs were calculated using a bottom-up approach and classified into direct medical and nonmedical costs, indirect costs, and patients' costs. RESULTS: Non-stroke-related costs (mean +/- standard deviation 4,610+/-9,310 Euros/person) were separated from total costs. Total stroke-related costs of the 4th year after stroke/TIA amounted to 7,670+/-10,250 Euros per person. The cost components were as follows: direct costs 56% (4,320+/-5,740 Euros), indirect costs 31% (2,350+/-2,710 Euros), and patients' payments 13% (1,000+/-4,100 Euros). The annual nationwide costs for the 4th year following stroke or TIA amounted to approximately 3 billion Euros. CONCLUSION: The considerable size of long-term costs after stroke/TIA is mainly due to direct costs and poses an economic challenge to the German health care system. Patients contribute in a relevant way by their own payments.


Subject(s)
Health Care Costs/statistics & numerical data , Ischemic Attack, Transient/economics , Ischemic Attack, Transient/epidemiology , Stroke/economics , Stroke/epidemiology , Aged , Female , Germany/epidemiology , Humans , Longitudinal Studies , Male , Prevalence
12.
Cancer Gene Ther ; 13(11): 993-1001, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16763608

ABSTRACT

Antiangiogenic gene therapy is a promising strategy for cancer treatment, which generally requires highly efficient delivery systems. To date, success of this strategy has depended almost exclusively on the delivery of high titers of viral vectors, which can result in effective transgene expression. However, their cytotoxicity and immunogenicity are a major concern for clinical applications. Recent advances in delivery efficiency of naked DNA could potentially meet the requirement for both high transgene expression and minimal side effects. To investigate whether naked DNA can be used for antiangiogenic cancer therapy, an expression plasmid was generated that encodes a soluble form of fetal liver kinase-1 (Flk-1) gene, a receptor for vascular endothelial growth factor (VEGF). Hydrodynamic injection of this plasmid resulted in close to 0.1 mg/ml of soluble Flk-1 protein in mouse serum and blocked VEGF-driven angiogenesis in matrigel in vivo. The same delivery significantly suppressed the growth of two different pre-existing subcutaneous tumors, Renca renal cell carcinoma and 3LL lung carcinoma. CD31 immunohistochemistry revealed that the tumor-associated angiogenesis was also highly attenuated in soluble Flk-1-treated mice. Thus, expression of genes by hydrodynamics-based gene delivery of naked DNA appears to be a promising approach for antiangiogenic cancer gene therapy.


Subject(s)
DNA/genetics , Genetic Therapy/methods , Neoplasms, Experimental/therapy , Vascular Endothelial Growth Factor Receptor-2/genetics , Animals , Cell Line , Cell Line, Tumor , Enzyme-Linked Immunosorbent Assay/methods , Female , Gene Transfer Techniques , Genetic Vectors/genetics , Humans , Immunohistochemistry , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Neoplasms, Experimental/blood supply , Neoplasms, Experimental/pathology , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/therapy , Plasmids/genetics , Platelet Endothelial Cell Adhesion Molecule-1/analysis , Vascular Endothelial Growth Factor A/genetics
13.
Acta Neurochir Suppl ; 89: 55-61, 2004.
Article in English | MEDLINE | ID: mdl-15335101

ABSTRACT

Histopathologic and NMR imaging studies show that focally ischemic brain lesions tend to increase in size over time. In animal models of stroke as well as in patients presenting with hemispheric stroke, considerable lesion growth was observed. In focal cerebral ischemia, lesions predominantly enlarge early (<12 hrs postinsult) and show complete ischemic injury due to pan necrosis in the vast majority of affected tissue. In global cerebral ischemia--a condition that is present after cardiac arrest--lesions appear late (>12 hrs) in selectively vulnerable brain regions and neurons are damaged by apoptosis. The short resuscitation time of the brain explains why periods of global ischemia result in widespread and global loss of energy metabolites combined with diffuse brain edema and global damage. Mechanisms involved in lesion growth include excitotoxicity, peri-infarct depolarizations, lactacidosis, microcirculatory disturbances, and flow-metabolism uncoupling among others. Problems involved in the subject under focus are related to maturation phenomena of injury and the different imaging modalities (metabolic imaging, NMR imaging, positron emission tomography) that require a subtly differentiated interpretation of the alterations observed.


Subject(s)
Brain Ischemia/pathology , Brain Ischemia/physiopathology , Brain/pathology , Brain/physiopathology , Neurons/pathology , Animals , Apoptosis , Brain/blood supply , Cerebrovascular Circulation , Disease Progression , Humans
14.
Nervenarzt ; 75(10): 991-9, 2004 Oct.
Article in German | MEDLINE | ID: mdl-15197452

ABSTRACT

BACKGROUND: Stroke care has a high impact on health costs. Therefore, the costs and reimbursements of integrated stroke care were calculated in a German neurological university hospital. PATIENTS AND METHODS: Patient cohorts of 2002 and 2003 were considered. All patients were included who presented with ischemic stroke, intracerebral hemorrhage, or transient ischemic attacks. G-DRG reimbursements were calculated by using the 3M grouper versions 2.2.0 for 2003 and 3.1 for 2004. RESULTS: There were no significant differences between the two patient cohorts. Compared to the former reimbursement system based on fixed daily charges, a base rate of EUR 3,204 was required for a neutral budget in 2002. The actual base rate was EUR 3,169. Assuming this base rate, an average reimbursement of EUR 4,201 (grouper 2.2.0) and of EUR 3,657 (grouper 3.1) was achieved per patient in 2002. An average reimbursement of EUR 4,107 (grouper 2.2.0) and of EUR 3,351 (grouper 3.1) was achieved per patient in 2003. CONCLUSION: The development of reimbursements by the G-DRGs shows a clear downward trend and shows that the high resource use in stroke unit care is inadequately reflected by the G-DRGs.


Subject(s)
Costs and Cost Analysis/methods , Diagnosis-Related Groups/economics , Health Care Costs/statistics & numerical data , Health Resources/economics , Insurance, Health, Reimbursement/economics , Stroke/economics , Stroke/therapy , Aged , Cohort Studies , Diagnosis-Related Groups/statistics & numerical data , Diagnosis-Related Groups/trends , Female , Germany/epidemiology , Health Care Costs/trends , Health Resources/statistics & numerical data , Health Resources/trends , Humans , Insurance, Health, Reimbursement/statistics & numerical data , Insurance, Health, Reimbursement/trends , Male , Retrospective Studies , Stroke/classification , Stroke/epidemiology
16.
Apoptosis ; 8(2): 151-60, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12766475

ABSTRACT

Lewis lung carcinoma (3LL) cells were constitutively resistant to Fas-mediated apoptosis, but overexpression of Fas on 3LL cells allowed Fas-mediated apoptosis after crosslinking with agonist anti-Fas antibody (Jo2) in vitro. Surprisingly, Fas-overexpressing 3LL cells showed enhanced in vivo tumor progression, whereas no promotion of in vivo tumor growth was observed for dominant negative (DN) Fas-overexpressing 3LL transfectants in which the cytoplasmic death domain was deleted. In addition, the promotion of in vivo tumor growth by Fas-overexpression was reduced in gld (FasL-mutation) mice compared to normal mice. These data indicate that intact Fas/FasL cell signaling is required for the promotion of in vivo tumor growth by Fas overexpression in 3LL cells. In contrast to the efficient Fas-mediated killing induced in vitro by crosslinking with anti-Fas antibody, Fas-overexpressing 3LL cells were resistant in vitro to Fas-mediated apoptosis by activated T cells or transient FasL transfection. These data suggest that agonist anti-Fas antibody and natural FasL can transmit qualitatively different signals, and crosslinking of Fas with natural FasL on 3LL cells does not deliver the expected death signal. Thus, our results demonstrate that in some cases overexpression of Fas can result in a survival advantage for tumor cells in vivo.


Subject(s)
Apoptosis , Carcinoma, Lewis Lung/pathology , Membrane Glycoproteins/physiology , Animals , Cell Division , Cross-Linking Reagents/pharmacology , Cytoplasm/metabolism , DNA/metabolism , Disease Progression , Fas Ligand Protein , Flow Cytometry , Genetic Vectors , Interferon-gamma/metabolism , Membrane Glycoproteins/metabolism , Mice , Mice, Inbred C57BL , Mutation , Neoplasms/pathology , Protein Structure, Tertiary , Signal Transduction , T-Lymphocytes/metabolism , Time Factors , Transfection , Up-Regulation
17.
Phytochemistry ; 58(7): 1043-7, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11730867

ABSTRACT

The bioactivity of 25-hydroxybrassinolide, (25S)- and (25R)-26-hydroxybrassinolide, (25S)- and (25R)-25,26-dihydroxybrassinolide, and of (25R)-25,26-epoxybrassinolide was tested in the rice leaf lamina inclination assay. The 25- and (25S)-26-hydroxy derivatives are known metabolites of the naturally-occurring phytohormone brassinolide, whereas the other compounds are novel, but closely related, congeners. When tested alone, all showed either no activity or only weak activity at relatively high doses. When coapplied with indole-3-acetic acid (IAA), an auxin that synergizes the effects of brassinosteroids, enhanced bioactivity was observed for each compound. However, even when applied together with IAA, none of the compounds proved more bioactive than brassinolide with or without IAA. We conclude from these results that enzymatic hydroxylation of endogenous brassinolide at C-25 and/or C-26 does not enhance brassinosteroid activity, and so does not comprise an activation pathway in brassinolide biosynthesis. Instead, these hydroxylations result in modest to appreciable metabolic deactivation.


Subject(s)
Cholestanols/metabolism , Oryza/metabolism , Steroids, Heterocyclic/metabolism , Brassinosteroids , Cholestanols/chemistry , Plant Leaves/metabolism , Steroids, Heterocyclic/chemistry
18.
J Org Chem ; 66(25): 8599-605, 2001 Dec 14.
Article in English | MEDLINE | ID: mdl-11735543

ABSTRACT

The palladium-catalyzed heteroannulation of o-iodoanilines with dienyl sulfones provides a convenient route to vinylogous 2-sulfonylindolines 3. The reaction proceeds in DMF/water in the presence of potassium carbonate and catalytic palladium(II) acetate and is compatible with both electron-donating and -withdrawing substituents in the para position of the aniline, and with an alkyl substituent at C-2 of the dienyl sulfone. The indolines underwent oxidation with DDQ to afford the corresponding indoles 4. The latter were then employed as dienes in Diels-Alder reactions with dimethyl acetylenedicarboxylate (DMAD), methyl propiolate, or methyl acrylate. In the case of the latter two dienophiles, the cycloadditions were highly regioselective, affording the corresponding 1,3-products (with respect to the relative positions of the sulfone and ester groups), exclusively. The cycloadducts from acetylenic dienophiles were converted to the corresponding carbazoles by elimination of the sulfone moiety with DBU, and that from methyl acrylate was subjected to reductive desulfonylation and oxidation to the corresponding carbazole with DDQ. The method thus provides access to carbazoles with various substituents at the 3-, 4-, and 6-positions.

19.
Neuroreport ; 12(18): 3943-6, 2001 Dec 21.
Article in English | MEDLINE | ID: mdl-11742216

ABSTRACT

Rats submitted to middle cerebral artery (MCA) clot embolism were treated with tissue plasminogen activator (TPA) 1.5 and 3.5 h post-occlusion. Reperfusion patterns were monitored by measuring cortical laser-Doppler flow; the direct current potential was measured to detect peri-infarct depolarizations (PID), a known mechanism of ischemic injury. TPA treatment induced reperfusion in 58% of treated animals that was delayed by 41 +/- 7 min (mean +/- s.e.m.) from treatment onset. The probability of reperfusion did not differ significantly between the two treatment groups. TPA treatment led to a 3-fold reduced frequency of PID if administered early or if successful reperfusion was observed (each p < 0.001). Early thrombolysis inhibits, but does not block, PID as an important mechanism of ischemic injury in embolic stroke.


Subject(s)
Cortical Spreading Depression/physiology , Infarction, Middle Cerebral Artery/physiopathology , Infarction, Middle Cerebral Artery/therapy , Thrombolytic Therapy , Animals , Cerebrovascular Circulation/physiology , Electroencephalography , Electrophysiology , Fibrinolytic Agents/pharmacology , Laser-Doppler Flowmetry , Male , Rats , Rats, Wistar , Tissue Plasminogen Activator/pharmacology
20.
In Vivo ; 15(4): 255-63, 2001.
Article in English | MEDLINE | ID: mdl-11695215

ABSTRACT

A significant splenomegaly and lymphadenopathy develops during the progressive growth of Lewis Lung (3LL) tumors in mice. Enlarged spleen and lymph nodes occur because of a pronounced increase in granulocytes in these organs. This granulocytosis in spleen and lymph node was not simply due to recruitment of granulocytes from peripheral blood to spleen and lymph nodes, but also a result of development and/or differentiation of granulocytes from the bone marrow. There was a marked increase in development of myeloid lineage cells, whereas lymphoid populations including T cells and B cells, were dramatically decreased in bone marrow and peripheral blood of 3LL tumor-bearing mice. These data demonstrate that host hematopoiesis shifts from lymphoid to granulocytic development in the 3LL tumor-bearing mice. Interestingly, a somatic mutation of N-Ras gene was found in 3LL tumor cells at codon 61, suggesting that mutated N-Ras may contribute to induction of granulocytosis in 3LL tumor-bearing mice.


Subject(s)
Carcinoma, Lewis Lung/pathology , Granulocytes/pathology , Hematopoiesis , Lymphocytes/pathology , Animals , Carcinoma, Lewis Lung/complications , Carcinoma, Lewis Lung/genetics , Carcinoma, Lewis Lung/metabolism , Cell Differentiation/genetics , Cell Lineage , Chemokines/biosynthesis , Chemokines/genetics , Codon/genetics , Gene Expression Regulation, Neoplastic , Genes, ras , Immunophenotyping , Interferon-gamma/deficiency , Interferon-gamma/genetics , Lymphatic Diseases/etiology , Lymphatic Diseases/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, SCID , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Neoplasm Transplantation , Neutrophils/pathology , Specific Pathogen-Free Organisms , Splenomegaly/etiology , Splenomegaly/pathology
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