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71.
Commonly used organophosphate pesticide dichlorvos is known to cause neurologic lesions. However, the exact mechanism of its neurotoxicity is, as yet, unclear. Using dose-dependent inhibition of acetylcholinesterase activity as an index of its neurotoxicity, effects of three different doses of dichlorvos (0.6 mg, 1.5 mg, and 3.0 mg/kg body weight i.p. daily for 10 days) have been observed on the rate of lipid-peroxidation in the cerebrum, cerebellum and brain stem of albino rats. Simultaneously, electron microscopic study of the dichlorvos intoxicated rat cerebellum was also carried out. Dose-dependent increase in the rate of lipid peroxidation was found in all the brain regions, and increased incidence of lipofuscin-like pigment granules was discernible in the Purkinie cells of the cerebellar cortex. 相似文献
72.
Population-based studies of childhood disability in developing countries: rationale and study design
Durkin M Zaman S Thorburn M Hasan M Davidson L 《International journal of mental health》1991,20(2):47-60
Infant mortality level has been used for decades to indicate the health and socioeconomic status of populations. Given the relative availability of necessary data, this indicator has proved most viable. As the more glaring aspects of underdevelopment fade into history in some countries, other health status indices should be considered. Childhood disability is proposed as 1 such indicator. Disability is neither subsumed by nor necessarily correlated with declining infant mortality, and may thus be used to help identify solutions for both short- and longterm problems. To employ this indicator, one needs to know how various types of disabilities are spread through populations as well as the correlated risk factors. Methodology must be developed which is capable of rapidly identifying cases and assessing risk factors. A 2-stage method, comprised of screening and clinical evaluation, is described. 相似文献
73.
74.
Pigmented liver cell adenoma in two male patients 总被引:2,自引:0,他引:2
We report two cases of hepatocyte neoplasia with extensive deposition of Dubin-Johnson-like pigment in men without Dubin-Johnson syndrome. This pigment has previously been described in hepatocellular carcinoma but not in liver cell adenoma. The tumors of both patients showed some atypical cytologic features, but no frank histologic evidence of malignancy. Long-term follow up for several years showed no evidence of recurrence after limited surgical excision. We conclude that tumors with this structure may be cured by limited surgical excision and should be considered as pigmented liver cell adenomas. 相似文献
75.
B. Ortel N. Chen J. Brissette G. P. Dotto E. Maytin T. Hasan 《British journal of cancer》1998,77(11):1744-1751
A treatment regimen that takes advantage of the induction of intracellular porphyrins such as protoporphyrin IX (PPIX) by exposure to exogenous 5-amino-laevulinic acid (ALA) followed by localized exposure to visible light represents a promising new approach to photodynamic therapy (PDT). Acting upon the suggestion that the effectiveness of ALA-dependent PDT may depend upon the state of cellular differentiation, we investigated the effect of terminal differentiation upon ALA-induced synthesis of and the subsequent phototoxicity attributable to PPIX in primary mouse keratinocytes. Induction of keratinocyte differentiation augmented intracellular PPIX accumulation in cells treated with ALA. These elevated PPIX levels resulted in an enhanced lethal photodynamic sensitization of differentiated cells. The differentiation-dependent increase in cellular PPIX levels resulted from several factors including: (a) increased ALA uptake, (b) enhanced PPIX production and (c) decreased PPIX export into the culture media. Simultaneously, steady-state levels of coproporphyrinogen oxidase mRNA increased but aminolaevulinic acid dehydratase mRNA levels remained unchanged. From experiments using 12-o-tetradecanoylphorbol-13-acetate, transforming growth factor beta 1 and calcimycin we demonstrated that the increase in PPIX concentration in terminally differentiating keratinocytes is calcium- and differentiation specific. Stimulation of the haem synthetic capacity is seen in primary keratinocytes, but not in PAM 212 cells that fail to undergo differentiation. Interestingly, increased PPIX formation and elevated coproporphyrinogen oxidase mRNA levels are not limited to differentiating keratinocytes; these were also elevated in the C2C12 myoblast and the PC12 adrenal cell lines upon induction of differentiation. Overall, the therapeutic implications of these results are that the effectiveness of ALA-dependent PDT depends on the differentiation status of the cell and that this may enable selective targeting of several tissue types. 相似文献
76.
77.
Huupponen E Värri A Himanen SL Hasan J Lehtokangas M Saarinen J 《Journal of medical systems》2000,24(3):183-193
Spindles are one of the most important short-lasting waveforms in sleep EEG. They are the hallmarks of the so-called Stage 2 sleep. Visual spindle scoring is a tedious workload, since there are often a thousand spindles in one all-night recording of some 8 hr. Automated methods for spindle detection typically use some form of fixed spindle amplitude threshold, which is poor with respect to inter-subject variability. In this work a spindle detection system allowing spindle detection without an amplitude threshold was developed. This system can be used for automatic decision making of whether or not a sleep spindle is present in the EEG at a certain point of time. An Autoassociative Multilayer Perceptron (A-MLP) network was employed for the decision making. A novel training procedure was developed to remove inconsistencies from the training data, which was found to improve the system performance significantly. 相似文献
78.
79.
Thomas Elter Peter Borchmann Holger Schulz Marcel Reiser Sven Trelle Roland Schnell Markus Jensen Peter Staib Timo Schink?the Hartmut Stützer Jürgen Rech Martin Gramatzki Walter Aulitzky Ibrahim Hasan Andreas Josting Michael Hallek Andreas Engert 《Journal of clinical oncology》2005,23(28):7024-7031
PURPOSE: To determine the efficacy and safety of a newly developed concomitant administration of fludarabine and alemtuzumab (FluCam) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). PATIENTS AND METHODS: A total of 36 patients were treated in this phase II study (median age, 61.47 years; mean number of prior chemotherapies, 2.6; Binet stage C, n = 28). After an initial dose escalation of alemtuzumab over 3 days, alemtuzumab 30 mg and fludarabine 30 mg/m2 were administered on 3 consecutive days. Treatment was repeated after 28 days for up to six cycles. Restaging (following National Cancer Institute criteria) was carried out after cycles 2 and 4 and 1 month after the end of treatment. RESULTS: The overall response rate was 83% (11 complete responses, 19 partial responses, one stable disease, and five progressive diseases). Two patients with progressive disease developed fungal pneumonias, and one patient died as a result of Escherichia coli sepsis. Two subclinical cytomegalovirus reactivations occurred. CONCLUSION: The new FluCam regimen is effective and feasible in patients with relapsed and refractory B-CLL. 相似文献
80.
Jurjees Hasan Steven D Shnyder Andrew R Clamp Alan T McGown Roy Bicknell Marco Presta Michael Bibby John Double Steven Craig David Leeming Kenneth Stevenson John T Gallagher Gordon C Jayson 《Clinical cancer research》2005,11(22):8172-8179
BACKGROUND: In previous experiments, we showed that heparin oligosaccharides inhibit the angiogenic cytokine fibroblast growth factor-2. Here, we present the first in vivo study of size-fractionated heparin oligosaccharides in four models of angiogenesis that are progressively less dependent on fibroblast growth factor-2. EXPERIMENTAL DESIGN: Heparin oligosaccharides were prepared using size-exclusion gel filtration chromatography and characterized through depolymerization and strong anion exchange high-performance liquid chromatography. Size-defined oligosaccharides (20 mg/kg/d) were given to mice bearing s.c. sponges that were injected with fibroblast growth factor-2 (100 ng/d). After 14 days, octasaccharides and decasaccharides reduced the microvessel density to levels below control. In a second experiment, HEC-FGF2 human endometrial cancer cells that overexpress fibroblast growth factor-2 were implanted in a hollow fiber placed s.c. in vivo. Oligosaccharides were given at 20 mg/kg/d for 2 weeks and the data again showed that octasaccharides significantly reduced microvessel density around the fiber (P = 0.03). In a more complex model, where angiogenesis was induced by a broad spectrum of growth factors, including vascular endothelial growth factor, we implanted H460 lung carcinoma cells in hollow fibers and treated the animals with oligosaccharides at 20 mg/kg/d over 3 weeks. Octasaccharides reduced the microvessel density to that of control. Preliminary investigation of 6-O-desulfated heparins showed that these also had antiangiogenic activity. RESULTS: Finally, we examined the inhibitory potential of hexasaccharides and octasaccharides given at 20 mg/kg/d and these inhibited the growth of H460 lung carcinoma in vivo. At clinically attainable concentrations, significant anticoagulation (activated partial thromboplastin time, anti-factor Xa, and anti-factor IIa) was not observed in vitro unless species containing > or =16 saccharide residues were investigated. CONCLUSIONS: Thus, our preclinical data show that heparin octasaccharides represent novel antiangiogenic compounds that can be given without the anticoagulant effects of low molecular weight heparin. 相似文献