julilili42/papers huggingface dataset:
Quantitative, phenotypic, and functional evaluation of basophils in myelodysplastic syndromes
2001-10-01

Background The myelodysplastic syndromes (MDS) are a group of clonal haematological disorders characterized by cytopenia(s), reduced differentiation‐capacity of myeloid cells, and impaired leukocyte function. However, little is known so far about basophil granulocytes in MDS. Design We have compared the numbers, phenotype and function of basophils in MDS patients with those in healthy subjects. A total numer of 23 patients with MDS (refractory anaemia, n = 8; refractory anaemia with ringsideroblasts, n = 7; refractory anaemia with excess of blasts/refractory anaemia with excess of blasts in transformation, n = 8) and 20 healthy donors were included. Results The numbers of blood basophils in MDS patients (34·6 ± 62·9 μL −1 ) was lower compared to healthy controls (58·6 ± 64·9 μL −1 ). Correspondingly, whole blood histamine levels were lower in MDS patients (MDS 34·1 ± 29·1 ng mL −1 vs. normal donors 72·0 ± 36·9 ng mL −1 ). Like ‘normal’ basophils, basophils in MDS expressed interleukin‐3 receptor α (CD123), E‐NPP3 (CD203c), CR1 (CD35), CR3 (CD11b), CR4 (CD11c), membrane co‐factor protein (CD46), decay‐accelerating factor (CD55) and membrane attack complex inhibitory factor (CD59), as well as receptors for C3a, C5a (CD88), and IgE. Recombinant human (rh) C5a and anti‐IgE induced significant release of histamine from basophils in both groups of donors without significant differences between MDS and healthy controls. Conclusions The absolute numbers of basophils in MDS patients are lower than in normal donors. However, basophils in MDS do not differ from their ‘normal counterparts’ in terms of complement receptor expression, IgE‐receptor expression, or functional responses to respective ligands.
Dopamine mediates striatal malonate toxicity via dopamine transporter‐dependent generation of reactive oxygen species and D2 but not D1 receptor activation
2001-10-01

Intrastriatal injection of the reversible succinate dehydrogenase inhibitor malonate results in both chemically induced hypoxia and striatal lesions that are similar to those seen in Huntington's disease and cerebral ischaemia. The mechanisms leading to neuronal death involve secondary excitotoxicity, the release of dopamine from nigrostriatal fibres and the generation of reactive oxygen species (ROS) including nitric oxide (NO) and hydroxyl radicals. Here, we further investigated the contribution and mechanism of dopamine on malonate‐induced striatal lesions. Prior lesions of the nigrostriatal pathway with 6‐OHDA or the depletion of striatal dopamine stores by pretreatment with reserpine, an inhibitor or the vesicular monoamine transporter type‐2 (VMAT2), in combination with α‐methyl‐p‐tyrosine resulted in a significant reduction of malonate‐induced striatal lesion volumes. This was paralleled by block or reduction of the malonate‐induced generation of ROS, as measured by the conversions of salicylate to 2,3‐dihydroxybenzoic acid (2,3‐DHBA) using microdialysis. Systemic or intrastriatal application of l ‐DOPA or dopamine, respectively, reconstituted malonate toxicity and the generation of ROS in 6‐OHDA‐lesioned rats. Block of the dopamine transporter by GBR12909 did not result in a reduction of malonate‐induced dopamine release, but significantly reduced the generation of hydroxyl radicals. The D2 receptor agonist lisuride and the mixed D1 and D2 receptor agonist apomorphine, but not the D1 receptor agonist SKF38393, partially restored malonate toxicity in 6‐OHDA‐lesioned rats without increasing the generation of ROS. In line with these results sulpiride, an inhibitor of D2 receptors, reduced the malonate‐induced lesion volume, whereas SCH23390, an inhbitor of D1 receptors, was ineffective. Our data suggest that malonate‐induced dopamine toxicity to energetically impaired neurons is mediated by two independent pathways: (i) dopamine transporter uptake‐dependent, dopamine receptor‐independent generation of ROS, and (ii) excessive stimulation of D2 receptors.
Cationic Amino Acids Involved in Dicarboxylate Binding of the Flounder Renal Organic Anion Transporter
2001-10-01

Three conserved cationic amino acids in predicted transmembrane domains 1, 8, and 11, respectively, of the flounder renal organic anion transporter, fROAT, were changed by site-directed mutagenesis and the resulting mutants functionally characterized in Xenopus laevis oocytes. Uptake of p-aminohippurate (PAH) in oocytes that expressed mutant H34I, K394A, or R478D was markedly reduced compared with oocytes that expressed wild-type fROAT, but was still several-fold higher than that in water-injected control oocytes. Immunocytochemically, no decrease in cell surface expression of the mutants could be detected. Only mutant R478D appeared to have a lower PAH affinity than the wild type. Similar to wild-type-dependent PAH transport, uptake induced by mutant H34I was sensitive to glutarate (GA) cis-inhibition. In contrast, mutants K394A and R478D could not be significantly affected by up to 10 mM GA, although the cRNA-dependent PAH uptake could still be almost completely suppressed by probenecid. Moreover, again in contrast to the wild type, neither PAH influx nor PAH efflux mediated by these two mutants could be trans-stimulated by GA, nor did they induce GA transport. These data suggest that amino acids K394 and R478 in fROAT are required for dicarboxylate binding and PAH/dicarboxylate exchange.
Non-cycloplegic screening for amblyopia via refractive findings with the Nikon Retinomax hand held autorefractor in 3 year old kindergarten children
2001-10-01

Non-cycloplegic refractive screening with the Retinomax led to many false positive referrals due to instrument myopia and "inconclusive" results. Hence specificity, accuracy, and the likelihood ratio were too low to conduct screening effectively.
Tertiary N-glucuronides of clozapine and its metabolite desmethylclozapine in patient urine.
2001-10-01

In experiments with expressed human UDP-glucuronosyltransferase 1A4 (UGT1A4), the antipsychotic clozapine proved to be conjugated to two different glucuronides, one of which was identified as the quaternary ammonium glucuronide derivatized at the N-methylpiperazine group; this compound had previously been isolated from patient urine. An additional glucuronide produced in larger quantity was assumed to be conjugated at the secondary nitrogen of the central ring to form 5-N-glucuronide, but this was not proven. The analogous olanzapine 10-N-glucuronide was found to make a major contribution to urinary metabolites in human volunteers. In the present investigation, tertiary 5-N-glucuronides were isolated from incubations of clozapine and desmethylclozapine with human liver microsomes fortified with UDP-glucuronic acid, and their structures were confirmed by mass and (1)H NMR spectrometry. The same conjugates could also be purified from patient urine. Their approximate quantities in urine from four patients ranged between 0.1 and 0.5% of the dose, as did those of the quaternary ammonium glucuronide of clozapine. Analogous to olanzapine 10-N-glucuronide, the tertiary clozapine 5-N-glucuronide was resistant toward enzymatic hydrolysis but was labile under acidic conditions.
Neural and Mechanical Factors in Eye Control
2001-10-01

Soft tissue “pulleys” in the orbit alter the paths of the eye muscles in a way that may simplify the brain's work in implementing Listing's law, i.e., in holding ocular torsion at zero. But Listing's law does not apply to some oculomotor systems, such as the vestibuloocular reflex (VOR), which shows a different kinematic pattern. To explain this different pattern, some authors have assumed that the pulleys must adopt a different configuration, retracting along their muscles when the eye switches from Listing's law to VOR mode. The proposed retraction has not so far been observed, although the pulleys do move in other ways. We show that the hypothetical retraction of the pulleys would not in fact explain the full kinematic pattern seen in the VOR. But this pattern can be explained entirely on the basis of pulley positions and motions that have actually been observed. If one takes into account the neural processing within the VOR, specifically the fact that the reflex is weak in the torsional dimension, then a single mode of pulley action can serve both vestibuloocular kinematics and Listing's law.
Points to Consider for Ethics Committees in Human Gene Therapy Trials
2001-10-01

Recent political developments and disclosures of serious adverse events in human gene therapy (HGT) with the death of 18‐year old Jesse Gelsinger in the USA have shown that the clinical application of HGT raises some severe ethical issues. These have either been neglected or not yet been discussed to a satisfactory extent. In this paper, we will address this deficiency and develop strategies for a safer application of HGT. Such a study must first look closely at the science of HGT itself. We will evaluate the latest preclinical research, especially data on the viruses that are used as vectors and on modes of administration of vectors. We will put forward new arguments concerning the toxicity assessment of so‐called ‘gene drugs‘, the tissue and cell type specificity of the vectors, and the duration and on‐set of gene expression. Secondly, we will look at procedural aspects of applied research ethics on the way to clinical application of HGT. There, informed consent (IC) and the patient‐researcher relationship are of utmost concern. Furthermore, we will explore the problem of expertise in risk assessment and will show how current regulations foster conflicts of interests that create dilemma situations even for those researchers who act in the best interest of the patients. We will conclude the article with a set of questions for ethicists who have to decide about the quality of HGT protocols. This may contribute to the safety of patients participating in HGT trials and to achieving the aim of efficient application of HGT.
Inhibition of Ret Oncogene Activity by the Protein Tyrosine Phosphatase SHP1
2001-10-01

Abstract Germline mutations in the Ret protooncogene give rise to the inherited endocrine cancer syndromes MEN types 2A and 2B and familiar medullary thyroid carcinoma. Although it is well accepted that the constitutive active tyrosine kinase of Ret oncogenes ultimately leads to malignant transformation, it is not clear whether a decrease in the autophosphorylation of oncogenic Ret forms can affect the mitogenic and transforming activities of Ret. Potential modulators of the tyrosine kinase activity of Ret could be tyrosine phosphatases that are expressed in human thyroid tissue. Therefore, we investigated the impact of the tyrosine phosphatases SHP1 and SHP2 on the intrinsic tyrosine kinase activity and oncogenic potency of Ret with a 9-bp duplication in the cysteine-rich domain (codons 634–636), which was described in a patient with MEN type 2A recently. SHP1 and SHP2 were stably overexpressed in NIH3T3 fibroblasts together with Ret-9bp. Coexpression of SHP1 with Ret-9bp reduced the autophosphorylation of Ret-9bp by 19 ± 7% (P = 0.01, n = 4), whereas no effect was seen with SHP2. Furthermore, Ret-9bp could be coimmunoprecipitated with SHP1 but not with SHP2 antibodies. Suppression of the Ret-9bp tyrosine kinase activity by SHP1 caused a decrease in activation of Erk2 (extracellular signal-regulated kinase) and abolished PKB/Akt (protein kinase B) phosphorylation. In addition, diminished Ret-9bp autophosphorylation led to reduced phosphorylation of the transcription factor jun-D. Finally, the inhibitory effect on Ret-9bp signaling resulted in a 40–60% reduction of[ 3H]thymidine incorporation and in reduced ability of NIH3T3 cells to form colonies in soft agar. In conclusion, the data suggest that SHP1 caused a moderate reduction of Ret autophosphorylation, which led to a strong suppression of the Ret oncogene activity.
Flow cytometric and histologic evaluation in a large cohort of patients with ulcerative colitis
2001-10-01

Because DNA aneuploidy represents an early alteration during neoplastic transformation in ulcerative colitis, flow cytometry is a valuable tool in the surveillance of those patients. Primary sclerosing cholangitis represents an additional risk factor for the development of DNA aneuploidy and dysplasia.
Remarks about the depth resolution of heterodyne interferometers in cochlear investigations
2001-10-01

Criteria of depth resolution of interferometric vibration measurements in the cochlea are discussed. Depending on the aim of the measurement, attention should be directed to the outer flank of the interference visibility curve, in contrast to the usual criterion of full width at half maximum. The depth at 30 dB suppression is proposed as a more appropriate criterion, when the measurement site is to be viewed through tissue.
Aesthetic Creativity, Reflexivity and the Play with Meaning: a VideoCulture case study
2001-10-01

ABSTRACT This article presents a case study of a video film called Die Liebe (Love, ) which was produced by two young girls from migrant family backgrounds in Ludwigsburg (Germany) as part of the VideoCulture project. In terms of production, the article describes the role played by the relatively open‐ended pedagogic style; the importance of aesthetic ‘discovery'; the uses of non‐linear editing; and the young people's sense of audience. In terms of reception, it describes the various responses of audience groups, focusing particularly on questions to do with the interpretation of symbolism and the balance between ‘openness’ and ‘closure’
Synthesen, Kristallstrukturen und magnetische Eigenschaften von [Li(12-Krone-4)2][Li(12-Krone-4)(OH2)]2[Nb6Cl18], [Li(15-Krone-5)2(OH2)]3[Nb6Cl18] und [(18-Krone-6)2(O2H5)]3[Nb6Cl18] / Syntheses, Crystal Structures and Magnetic Behaviour of [Li(12-Krone-4)2][Li(12-Krone-4)(OH2)]2[Nb6Cl18], [Li(15-Krone-5)2(OH2)]3[Nb6Cl18] and [(18-Krone-6)2(O2H5)]3[Nb6Cl18]
2001-10-01

The title compounds were prepared through reactions of Li 2 Nb 6 Cl 16 with the corresponding crown ethers in acetone. All three compounds were obtained as dark brown crystals. Their structures were solved with the means of single-crystal X-ray diffraction. [Li(12-crown-4) 2 ][Li(12-crown-4)(OH 2 )] 2 [Nb 6 Cl 18 ]: space group P2 1 /n, Z =2, a = 1320.4(1), b = 1879.1(1), c = 1321.7(1) pm, ß = 92.515(6)°, R 1 = 0.0297 (I&gt;2σ(I)). The crystal structure contains Li + sandwiched by two 12-crown-4-ethers plus Li + coordinated by one 12-crown-4- ether and one water molecule. [Li(15-crown-5) 2 (OH 2 )] 3 [Nb 6 Cl 18 ]: space group R3̅, Z = 3, a = b = 2081.7(1), c = 1991.7(1) pm, R 1 = 0.0395 (I &gt; 2σ(I)). In the crystal structure Li + and one water molecule are sandwiched by two 15-crown-5-ethers. [(18-crown-6) 2 (O 2 H 5 )] 3 [Nb 6 Cl 18 ]: space group P1̅, Z = 1 ,a = 1405.1(1), b = 1461.1(2), c = 1492.2(2) pm; α = 98.80(1)°, ß = 98.15(1)°, γ = 97.41(1)°, R 1 = 0.0538 (I &gt; 2σ(I)). H 5 O 2 + was found in the structure refinement sandwiched between two 18-crown-6-ethers. All compounds reported contain [Nb 6 Cl 18 ] clusters with Nb-Nb distances between 299 and 301 pm. The paramagnetic behaviour expected for [Nb 6 Cl 18 ] 3- in all three compounds was confirmed by magnetic measurements.
Developing a stage lighting system from scratch
2001-10-01

Lula is a system for computer-assisted stage lighting design and control. Whereas other systems for the same purpose are usually the results of long chains of incremental improvements of historic concepts, Lula represents a complete redesign. Whereas other systems focus on control aspects of lighting, Lula focuses on design and generates control information from it. This approach gives significantly more flexibility to the lighting designer and shortens the design process itself. Lula's design and implementation draw from a number of disciplines in advanced programming. It is written in Scheme and runs atop PLT Scheme, and benefits from its high-level GUI library. Lula uses an algebraic model for lighting looks based on just three combinators. It employs Functional Reactive Programming for all dynamic aspects of lighting, and is programmable via a functional reactive domain-specific language. Lula is an actual product and has users who have neither interest in nor knowledge of functional programming.
Total Implantation of the Active Hearing Implant Tica for Middle Ear Disease: A Temporal Bone Study
2001-10-01

A subpopulation of hearing-impaired patients has conductive hearing loss that cannot be improved by classic tympanoplasty. Other patients have a mixed hearing loss and cannot be helped by present forms of ear surgery or by hearing aids. Possible help for some patients may come from current implantable hearing devices if these are modified for the patient's specific anatomic situation. The TICA LZ 3001 is a hearing implant for total implantation used to treat moderate to severe sensorineural hearing loss. Most patients who use it have a normal ossicular chain that allows coupling of the implant to the incus. The present temporal bone study demonstrates that the TICA can also be used in patients with an interrupted ossicular chain. If the incus long process shows a defect, the TICA may be coupled to the incus body, and connection between the stapes and the long process of the incus can be achieved with a commercially available titanium-angle prosthesis or liquid ionomeric cement. In cases of an absent incus, the coupling axis of the transducer may be coupled to the stapes head via a modified coupling element. With an absent stapes, the coupling axis may be coupled directly to the perilymph by a coupling element similar to a gold stapes prosthesis.
Bcl-2 is not required in retinal ganglion cells surviving optic nerve axotomy
2001-10-01

Axotomy of the optic nerve in rodents induces the majority of retinal ganglion cells (RGCs) to undergo apoptosis: Only 10-15% survive 14 days past lesion. The molecular mechanism allowing this survival is not known. To test whether expression of the anti-apoptotic proto-oncogene bcl-2 gene is required in those RGCs, we examined the effect of optic nerve axotomy in bcl-2-/- mice. 7 days and 14 days post-lesion, the same number of surviving RGCs was detected in mutant and wild type retinas. Thus, the bcl-2 gene is not necessary for the survival of the subpopulation of retinal ganglion cells resisting axotomy-induced apoptosis in adult mice, nor does its normal expression delay retinal ganglion cell degeneration.
Ultrafast Reflection Control based on Photoinduced Complex Refractive Index Changes in Guided Mode Thin Films Containing Indium Phthalocyanine
2001-10-01

Abstract Ultrafast all-optical reflection control was achieved by complex refractive index changes upon photoexcitation of indium phthalocyanine in a guided mode geometry device. It gave a few microseconds response mostly characteristic to the lifetime of the excited triplet state.
Analysis of heat‐shock transcription factor–DNA binding in Arabidopsis suspension cultures by UV laser crosslinking
2001-10-01

Summary Crosslinking techniques are important in examining protein–DNA interactions in living cells. Formaldehyde and UV light emitted by conventional lamps are the most commonly used crosslinking agents. The crosslinking step is followed by immunoprecipitation of specific protein–DNA adducts, and by analysis and quantification of the co‐immunoprecipitated DNA. There are a few reported cases of fruitful in vivo protein–DNA crosslinking experiments, but not in plants. In this report, we analyse the binding of heat‐shock transcription factor (HSF) to heat‐shock promoters in intact Arabidopsis cells. Efficient protein–DNA crosslinking by irradiation of Arabidopsis suspension culture tissue was achieved using UV laser pulses. In addition, methods for immunoprecipitation and detection of the co‐immunoprecipitated DNA are reported. Our results suggest that Arabidopsis HSFs immunoreactive for HSF1 antibodies bind constitutively to the HSP18.2 gene.
Induction of differentiation and tetraploidy by long-term treatment of C6 rat glioma cells with erucylphosphocholine
2001-10-01

Induction of differentiation represents a promising concept for chemotherapy of malignant gliomas, which are often refractory even to the combined treatment with surgery, irradiation and chemotherapy. Since anti-neoplastic alkylphosphocholines can induce differentiation of leukemic cell lines, the effects of the intravenously applicable alkylphosphocholine-derivative erucylphosphocholine (ErPC) on proliferation, morphology and differentiation of the rat glioma cell line C6 was examined in vitro. Short-term exposure to ErPC induced accumulation of the cells in the G2/M-phase of the cell cycle and apoptotic cell death. In contrast, continuous exposure of C6 rat glioma cells to sublethal ErPC doses (30 and 50 microM) caused both the formation of a slower growing tetraploid cell population and astrocytic differentiation. No resistance to in vivo obtainable ErPC concentrations was observed during this treatment. We conclude that ErPC-induced differentiation might be beneficial for a long-term adjuvant chemotherapy of low grade glioma.
NUCLEON FORM FACTORS IN THE COVARIANT DIQUARK–QUARK MODEL
2001-10-01

The nucleon is described as a bound state of a quark and an extended diquark. Hereby the notion ``diquark'' refers to the modelling of separable correlations in the two-quark Green's functions. Binding of quarks and diquarks takes place via an exchange interaction and is therefore related to the Pauli principle for three-quark states. Fully Poincare covariant nucleon amplitudes are calculated for free constituent propagators as well as for dressed propagators which parameterise confinement. The corresponding results for space-like form factors differ quantitatively but not qualitatively for various ans\\"atze for the propagators. These results do not allow to draw definite conclusions on the permissibility of different dressing functions. Results for kaon photoproduction, on the other hand, exclude a whole class of constituent propagators.
Viviparus ater Hemocyanin: Investigation of the Dioxygen-Binding Site and Stability of the Oxy- and Apo-Forms
2001-10-01

Abstract The active site of Viviparus ater (mollusc) hemocyanin was investigated using the fact that the binding of dioxygen to the binuclear copper-containing sites of hemocyanins is connected with the appearance of specific dichroic bands which are very sensitive to changes in the structrure and polarity of the environment. Oxy-Viviparus ater hemocyanin exhibits near UV and visible circular dichroism spectra different from those of other molluscan and arthropo-dan hemocyanins. These differences are due probably to variations in the geometry or charge distribution in the dioxygen binding sites of the compared proteins. The thermostability of Viviparus ater hemocyanin and the significance of the copper-dioxy-gen system for the stability were also investigated. “Melting” temperatures, T m , of 77 °C for the oxy-hemocyanin and 57 °C for the apo-protein were calculated from the denaturation curves which demonstrates the considerable role of the binuclear active site for the thermostability. Viviparus ater hemocyanin is more thermostable than other hemocyanins for which data are published.