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81.
Yu WH Zhao KW Ryazantsev S Rozengurt N Neufeld EF 《Molecular genetics and metabolism》2000,71(4):573-580
The Sanfilippo syndrome type B (MPS III B) is an autosomal recessive disease caused by deficiency of alpha-N-acetylglucosaminidase (EC 3. 2.1.50), one of the lysosomal enzymes required for the degradation of heparan sulfate. The disease is characterized by profound neurodegeneration but relatively mild somatic manifestations, and is usually fatal in the second decade. A mouse model had been generated by disruption of the Naglu gene in order to facilitate the study of pathogenesis and the development of therapy for this currently untreatable disease. Recombinant human alpha-N-acetylglucosaminidase (rhNAGLU) was prepared from secretions of Lec1 mutant Chinese hamster ovary cells. The enzyme, which has only unphosphorylated high-mannose carbohydrate chains, was endocytosed by mouse peritoneal macrophages via mannose receptors, with half-maximal uptake at ca. 10(-7) M. When administered intravenously to 3 month-old mice, rhNAGLU was taken up avidly by liver and spleen but marginally if at all by thymus, lung, kidney, heart, and brain (in order of diminishing uptake). The half-life of the enzyme was 2.5 days in liver and spleen. Immunohistochemistry and electron microscopy showed that only macrophages were involved in enzyme uptake and correction in these two organs, yet the storage of glycosaminoglycan was reduced to almost normal levels. The results show that the macrophage-targeted rhNAGLU can substantially reduce the body burden of glycosaminoglycan storage in the mouse model of Sanfilippo syndrome III B. 相似文献
82.
Newman JT Surman SR Riggs JM Hansen CT Collins PL Murphy BR Skiadopoulos MH 《Virus genes》2002,24(1):77-92
A complete consensus sequence was determined for the genomic RNA of human parainfluenza virus type 1 (HPIV1) strain Washington/20993/1964 (HPIV1 WASH/64), a clinical isolate that previously was shown to be virulent in adults. The sequence exhibited a high degree of relatedness to both Sendai virus, a PIV1 virus recovered from mice, and human PIV3 (HPIV3) with regard to cis-acting regulatory regions and protein-coding sequences. This consensus sequence was used to generate a full-length antigenomic cDNA and to recover a recombinant wild-type HPIV1 (rHPIV1). Interestingly, the rHPIV1 could be rescued from full-length antigenomic rHPIV1 cDNA using HPIV3 support plasmids, HPIV1 support plasmids, or a mixture thereof. The replication of rHPIV1 in vitro and in the respiratory tract of hamsters was similar to that of its biologically derived parent virus. The similar biological properties of rHPIV1 and HPIV1 WASH/64 in vitro and in vivo, together with the previous demonstration of the virulence of this specific isolate in humans, authenticates the rHPIV1 sequence as that of a wild-type virus. This rHPIV1 can now be used to study the biological properties of HPIV1 and as a substrate to introduce attenuating mutations for the generation of live-attenuated HPIV1 vaccine candidates.An erratum to this article can be found at 相似文献
83.
Oxidative capacity interacts with oxygen delivery to determine maximal O2 uptake in rat skeletal muscles in situ 总被引:2,自引:1,他引:2
When intracellular recordings were made from the antral region of murine stomach, cells with three different patterns of electrical activity were detected. One group of cells generated follower potentials, the second group generated pacemaker potentials and the third group generated slow waves that consisted of primary and secondary components. Slow waves recorded in different regions of the gastric antrum had similar amplitudes but different characteristic shapes. At the greater curvature, slow waves had large initial components. Midway between the greater and lesser curvature, the amplitude of the initial component was reduced and at the lesser curvature an initial component was difficult to detect. When the distributions of myenteric (ICC-MY) and intramuscular interstitial cells of Cajal (ICC-IM) were determined, using an antibody to Kit, ICC-MY were found to be present at the greater curvature but were greatly reduced in density at the lesser curvature. In contrast, ICC-IM were found in the circular layer of each region. When recordings were made from the antrum of W/WV mice, which lack ICC-IM, incomplete slow waves were detected and their amplitudes fell from the greater to the lesser curvature. Again, a corresponding fall in the density of ICC-MY was detected. The observations indicate that the contribution of ICC-MY and ICC-IM to the generation of slow waves varies in different regions of the mouse gastric antrum. 相似文献
84.
Tumor Vascularity Is Not a Prognostic Factor for Malignant Melanoma of the Skin 总被引:1,自引:4,他引:1
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Klaus J. Busam Marianne Berwick Karen Blessing Katrin Fandrey Sewon Kang Themis Karaoli Judy Fine Alistair J. Cochran Wain L. White Jason Rivers David E. Elder Duan-Ren Po Wen Bradley H. Heyman Raymond L. Barnhill 《The American journal of pathology》1995,147(4):1049-1056
Tumor vascularity has been proposed as a prognostic indicator for a number of solid tumors. Although a correlation between microvessel number and metastatic behavior has also been suggested for cutaneous melanoma, the small number of cases studied to date allows one to draw only preliminary conclusions. In this study, we have assessed tumor vascularity in cutaneous melanoma by comparing 60 cases of metastasizing and non-metastasizing tumors matched for tumor thickness, age, sex, and anatomic site. Ulex europaeus agglutinin I appeared to be the most suitable vascular marker for this study. Our results indicate that there was no statistically significant difference between the two groups with regard to tumor vascularity. Even after identifying 15 cases of thin (<1.0 mm thick) melanoma, there was no significant difference in the number of microvessels between metastasizing and non-metastasizing tumors. Comparison of patterns of vascular microarchitecture also failed to discriminate between the two groups. Thus, our results indicate that tumor vascularity may not be an independent prognostic factor for cutaneous melanoma. 相似文献
85.
Jason LA Jordan KM Richman JA Rademaker AW Huang CF McCready W Shlaes J King CP Landis D Torres S Haney-Davis T Frankenberry EL 《Journal of health psychology》1999,4(1):9-26
Previous estimates of the prevalence of fatigue and chronic fatigue have derived largely from treated populations and have been biased by differential access to health-care treatment linked with gender, racial/ethnic and social class status. This study involves a community-based prevalence study of prolonged fatigue and chronic fatigue. It addresses: (1) the rate of prolonged fatigue and chronic fatigue in a socioeconomically and ethnically diverse sample of 28,673 adults in Chicago; and (2) establishes the relative prevalence of prolonged fatigue and chronic fatigue across race/ethnicity, socio-economic status and gender. Univariate and multivariate statistical techniques were utilized to delineate the overall rate of prolonged fatigue and chronic fatigue in the Chicago population and its relative prevalence by gender, race/ethnicity, and social class. Findings indicated that fatigue is common in urban populations, but that prolonged fatigue and chronic fatigue occur in about 5.00 to 7.68 percent and 2.72 to 4.17 percent, respectively, of the sample of the population. Highest levels of fatigue were consistently found among women and those with lower levels of education and occupational status. 相似文献
86.
Anjali Ramaswamy Nina N. Brodsky Tomokazu S. Sumida Michela Comi Hiromitsu Asashima Kenneth B. Hoehn Ningshan Li Yunqing Liu Aagam Shah Neal G. Ravindra Jason Bishai Alamzeb Khan William Lau Brian Sellers Neha Bansal Pamela Guerrerio Avraham Unterman Victoria Habet Carrie L. Lucas 《Immunity》2021,54(5):1083-1095.e7
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87.
DeBruyne J Hurd MW Gutiérrez L Kaneko M Tan Y Wells DE Cahill GM 《Journal of neurogenetics》2004,18(2):403-428
Widespread use of zebrafish (Danio rerio) in genetic analysis of embryonic development has led to rapid advances in the technology required to generate, map and clone mutated genes. To identify genes involved in the generation and regulation of vertebrate circadian rhythmicity, we screened for dominant mutations that affect the circadian periodicity of larval zebrafish locomotor behavior. In a screen of 6,500 genomes, we recovered 8 homozygous viable, semi-dominant mutants, and describe one of them here. The circadian period of the lager and lime (lag(dg2)) mutant is shortened by 0.7 h in heterozygotes,and 1.3 h in homozygotes. This mutation also shortens the period of the melatonin production rhythm measured from cultured pineal glands, indicating that the mutant gene product affects circadian rhythmicity at the tissue level, as well as at the behavioral level. This mutation also alters the sensitivity of pineal circadian period to temperature, but does not affect phase shifting responses to light. Linkage mapping with microsatellite markers indicates that the lag mutation is on chromosome 7. A zebrafish homolog of period1(per1) is the only known clock gene homolog that maps near the lag locus. However, all sequence variants found in per1 cDNA from lag(dg2) mutants are also present in wild type lines, and we were unable to detect any defect in per1 mRNA splicing, so this mutation may identify a novel clock gene. 相似文献
88.
Effects of a brisk walk on lipoprotein lipase activity and plasma triglyceride concentrations in the fasted and postprandial states 总被引:3,自引:0,他引:3
This study aimed to determine whether changes in plasma heparin-releasable lipoprotein lipase (LPL) activity following a brisk
walk were associated with decreases in fasting and/or postprandial triglyceride (TG) concentrations. Two groups of pre-menopausal
women participated. In one group (fasting study group, n=10), TG concentrations and post-heparin plasma LPL activity were measured in the fasted state on two occasions: ~18 h after
a 2-h treadmill walk at 50% maximal oxygen uptake (exercise trial); and after a day of no exercise (control trial). The other
group (postprandial study group, n=9) undertook two oral fat tolerance tests (blood samples taken fasting and for 6 h after a high-fat meal), with plasma LPL
activity measured 6 h after meal ingestion. Pre-conditions were the same as for the fasting study group (i.e. control and
prior exercise). Prior exercise reduced fasting TG concentrations by 23 (7)% (fasting study group) [mean (SEM)] and by 18
(9)% (postprandial study group) (both P<0.05), and the postprandial TG response by 23 (6)% (postprandial study group) (P<0.01). Plasma LPL activity was not significantly increased by exercise in either the fasting or postprandial study groups.
However, exercise-induced changes in both fasting and postprandial LPL activity were significantly correlated with the respective
exercise-induced changes in fasting TG concentration and the postprandial TG response (r=−0.70 and −0.77 respectively, P<0.05 for both). These data suggest that increased LPL activity may contribute to the hypotriglyceridaemic effect of moderate
exercise, although other mechanisms are also likely to be involved.
Electronic Publication 相似文献
89.
Effects of Colloidal Resuscitation Fluids on Reticuloendothelial Function and Resistance to Infection after Hemorrhage 总被引:3,自引:0,他引:3
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Ed A. M. van Rijen Jason J. Ward Roderick A. Little 《Clinical and Vaccine Immunology : CVI》1998,5(4):543-549
The effects of three resuscitation fluids, hydroxyethyl starch (HES), Haemaccel, and fresh autologous blood, on reticuloendothelial system phagocytic and catabolic functions and resistance to infection after 40% hemorrhages in BALB/c mice were studied. The mice, anesthetized with isoflurane, were bled over a 10-min period, left hypovolemic for 30 min, and then resuscitated with their shed blood or the same volume of asanguineous fluid. Normothermia was maintained throughout the experiments. The uptake and catabolism of intravenously injected double-labelled sheep erythrocytes (51Cr-125I-SRBC) in liver and spleen were determined at 1 and 48 h after hemorrhage. No significant changes in the uptake or catabolism of SRBC in liver or spleen were found at 1 h after hemorrhage and resuscitation with any of the fluids. However, at 48 h a significant increase in liver uptake of SRBC was seen in animals resuscitated with either Haemaccel or HES compared to that in animals resuscitated with shed blood or in animals subjected to a sham operation. The increase in liver uptake was accompanied by a small decrease in spleen uptake in animals resuscitated with Haemaccel but not with HES. No great changes in catabolic activity were seen at 48 h, although activity levels tended to be higher in animals resuscitated with Haemaccel. Separate groups of animals were challenged by an intraperitoneal injection with live Escherichia coli at 1 or 48 h after hemorrhage and resuscitation. Sixty-four percent of the animals resuscitated with shed blood survived the challenge with E. coli at 1 h after hemorrhage, whereas only 10 and 0% survival was seen for animals resuscitated with Haemaccel and HES, respectively. At 48 h survival was 80% for shed-blood-resuscitated animals and 60 and 70% for Haemaccel- and HES-resuscitated animals, respectively. 相似文献
90.
Henrik Toft-Hansen Alicia A Babcock Jason M Millward Trevor Owens 《Journal of neuroinflammation》2007,4(1):24