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51.
52.
M A Ostrowski J X Gu C Kovacs J Freedman M A Luscher K S MacDonald 《The Journal of infectious diseases》2001,184(10):1268-1278
The human immunodeficiency virus type 1 (HIV-1)-specific CD4(+) T cell response was investigated in 33 untreated HIV-1-infected individuals, using highly sensitive ELISPOT assays and intracellular flow cytometry. The median frequencies of interferon (IFN)-gamma-producing HIV-1 gag-specific CD4(+) T cells did not correlate significantly with control of viral replication or progression. HIV-1 gag-specific interleukin (IL)-4-producing cells were rarely detected. Circulating frequencies of CD4(+) T cells constitutively producing IL-10, however, were significantly higher in individuals with progression or active replication. In 17 of 30 HIV-1-infected individuals, gag antigen was observed to induce IL-10 production from CD4(+) T cells. In 2 individuals, early treatment of acute HIV-1 infection "rescued" low to undetectable gag-specific IFN-gamma-producing CD4(+) T cell responses and dramatically down-regulated constitutive IL-10 production from circulating CD4(+) T cells. The detection of HIV-1-specific IL-10-inducing CD4(+) T cells in HIV-1-infected individuals suggests that HIV-1 may directly subvert specific immune responses by IL-10 induction. 相似文献
53.
Warren A Chaberek S Ostrowski K Cogger VC Hilmer SN McCuskey RS Fraser R Le Couteur DG 《Microcirculation (New York, N.Y. : 1994)》2008,15(3):191-202
OBJECTIVES: In old age, there are marked changes in both the structure of the liver sinusoidal endothelial cell and liver perfusion. The objective of this study was to determine whether there are also aging changes in the microvascular architecture and vascular dispersion of the liver that might influence liver function. METHODS: Vascular corrosion casts and light micrographs of young (4 months) and old (24 months) rat livers were compared. Fractal and Fourier analyses and micro-computed tomography were used. Vascular dispersion was determined from the dispersion number for sucrose and 100-nm microspheres in impulse response experiments. RESULTS: Age did not affect sinusoidal dimensions, sinusoidal density, or dispersion number. There were changes in the geometry and complexity of the sinusoidal network as determined by fractal dimension and degree of anisotropy. CONCLUSIONS: There are small, age-related changes in the architecture of the liver sinusoidal network, which may influence hepatic function and reflect broader aging changes in the microcirculation. However, sinusoidal dimensions and hepatic vascular dispersion are not markedly influenced by old age. 相似文献
54.
Thrombopoietin (Tpo), the ligand for the c-Mpl receptor, is a major regulator of megakaryopoiesis. Treatment of mice with Tpo raises the platelet count fourfold within a few days. Conversely, c-mpl knock-out mice have platelet counts that are 15% that of normal. The subunit structure of the c-Mpl receptor is not fully understood. Some cytokines that stimulate megakaryopoiesis (IL-6, IL-11, leukemia inhibitory factor, and oncostatin M) bind to receptors that use gp130 as a signal transduction subunit. For these reasons, we determined whether gp130 function was required for Tpo-induced signal transduction. Murine marrow cells were cultured in semi-solid media in the presence of Tpo or IL-3, with or without a neutralizing anti-gp130 monoclonal antibody (RX187) or a soluble form of c-Mpl receptor (soluble Mpl) that blocks Tpo bioactivity, and the numbers of colony-forming unit-megakaryocyte (CFU-Meg) colonies were counted on day 5. Murine marrow cells were also cultured in suspension under serum-free conditions for 5 days, and megakaryocyte DNA content was measured by flow cytometry, as an index of nuclear maturation. The addition of RX187 did not block Tpo-induced CFU-Meg colony growth nor CFU-Meg nuclear maturation in suspension culture. However, IL-3-induced CFU-Meg colony growth and megakaryocyte nuclear maturation decreased in the presence of RX187. Soluble Mpl completely ablated Tpo-induced CFU-Meg growth, and partially blocked IL- 3-stimulated CFU-Meg growth. Thus the effects of Tpo on megakaryopoiesis in vitro do not depend on cytokines that signal through gp130. Furthermore, it is unlikely that gp 130 serves as a beta chain for the c-Mpl receptor, as Tpo signalling is unimpaired in the presence of RX187. In contrast, the effects of IL-3 on CFU-Meg growth are mediated in part through Tpo and through gp130-signalling cytokines. 相似文献
55.
We asked how processing of male signals in the auditory pathway of the bush cricket Ancistrura nigrovittata (Phaneropterinae, Tettigoniidae) changes from the ear to the brain. From 37 sensory neurons in the crista acustica single elements (cells 8 or 9) have frequency tuning corresponding closely to the behavioral tuning of the females. Nevertheless, one‐quarter of sensory neurons (approximately cells 9 to 18) excite the ascending neuron 1 (AN1), which is best tuned to the male's song carrier frequency. AN1 receives frequency‐dependent inhibition, reducing sensitivity especially in the ultrasound. When recorded in the brain, AN1 shows slightly lower overall activity than when recorded in the prothoracic ganglion close to the spike‐generating zone. This difference is significant in the ultrasonic range. The first identified local brain neuron in a bush cricket (LBN1) is described. Its dendrites overlap with some of AN1‐terminations in the brain. Its frequency tuning and intensity dependence strongly suggest a direct postsynaptic connection to AN1. Spiking in LBN1 is only elicited after summation of excitatory postsynaptic potentials evoked by individual AN1‐action potentials. This serves a filtering mechanism that reduces the sensitivity of LBN1 and also its responsiveness to ultrasound as compared to AN1. Consequently, spike latencies of LBN1 are long (>30 ms) despite its being a second‐order interneuron. Additionally, LBN1 receives frequency‐specific inhibition, most likely further reducing its responses to ultrasound. This demonstrates that frequency‐specific inhibition is redundant in two directly connected interneurons on subsequent levels in the auditory system. J. Comp. Neurol. 518:3101–3116, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
56.
Pulmonary lymphangiomyomatosis: correlation of CT with radiographic and functional findings 总被引:3,自引:0,他引:3
In 14 patients with biopsy-proved lymphangiomyomatosis, disease extent at computed tomography (CT) was correlated with findings at chest radiography and pulmonary-function testing. The CT scans and chest radiographs were read independently by two chest radiologists. Disease extent was assessed on CT scans by using a visual score (0%-100% involvement of the lung parenchyma) and on radiographs by using an adaptation of the International Labour Office classification of the pneumoconioses. There was good concordance between the two observers for CT and radiographic scores (Kendall tau greater than or equal to .86, P less than .01). A significant but relatively low correlation was present between CT findings and radiographic severity of disease (r = .59, P less than .05). Impairment in gas exchange as assessed with the diffusing capacity correlated better with disease extent seen on CT scans (r = .69) than with chest radiographic findings (r = .59). Three patients had evidence of parenchymal disease on the CT scans but not on the radiographs. In one patient CT findings were negative despite a positive finding on chest radiographs. The authors conclude that CT is superior to chest radiography in the assessment of patients with lymphangiomyomatosis. 相似文献
57.
58.
Steroid withdrawal at 3 months after kidney transplantation: a comparison of two tacrolimus-based regimens 总被引:3,自引:0,他引:3
Zbigniew Wlodarczyk Janusz Walaszewski Ferenc Perner Stefan Vitko Marek Ostrowski Petr Bachleda Franciszek Kokot Marian Klinger Pal Szenohradszky Pavel Studenik Pavel Navratil Laszlo Asztalos Boleslaw Rutkowski Karoly Nagy Kalmar David Hickey 《Transplant international》2005,18(2):157-162
The 6 month prospective, randomized study compared the steroid-sparing potential of two tacrolimus-based regimens after renal transplantation. A total of 489 patients were randomized (1:1) to receive tacrolimus/mycophenolate mofetil (MMF)/steroids (n = 243; group Tac/MMF/S) or tacrolimus/azathioprine/steroids (n = 246; group Tac/Aza/S). At 3 months, steroids were tapered off in 267 (54.6%) patients free from steroid-resistant acute rejection and with serum creatinine concentrations <160 micromol/l. The incidence of biopsy-confirmed acute rejection at month 3 was lower in group Tac/MMF/S compared with group Tac/Aza/S (18.1% vs. 26.0%,P = 0.035). Moreover, more patients in the Tac/MMF/S group met the criteria for steroid withdrawal than in the Tac/Aza/S group (60.5% vs. 48.8%; P < 0.01). The incidence of acute rejection during months 4-6 was low in all groups, both for patients on steroid-free dual therapy (Tac/MMF: 2.7%, Tac/Aza: 0.8%) and for patients who continued steroid maintenance therapy (Tac/MMF/S: 3.5%, Tac/Aza/S: 7.1%). Moreover, kidney function was well preserved in steroid-free patients with month 6 median serum creatinine levels of 119.5 micromol/l (Tac/MMF), and 115.1 micromol/l (Tac/Aza). For patients who continued to receive steroids, month 6 median creatinine levels were 130.5 micromol/l (Tac/MMF/S) and 132.8 micromol/l (Tac/Aza/S). The criteria for the selection of patients to discontinue steroids were adequate. Both tacrolimus-based regimens allowed the safe discontinuation of steroids in low-risk patients at month 3. The Tac/MMF combination was superior in the prevention of acute rejections and more patients met the chosen criteria for steroid withdrawal. 相似文献
59.
Mieczysaw Pokorski Zdzisaw Matysiak Magdalena Marczak Robert P. Ostrowski Andrzej Kapuciski Iwona Matuszewska Marianna Kaska Zbigniew Czarnocki 《Drug development research》2003,60(3):217-224
N‐acyl‐dopamines are a novel class of biologically active lipids that have recently been identified in the brain and have the potential to interact with neural signaling pathways. This study seeks to determine the ability of N‐oleoyl‐dopamine, a synthetic amide of oleic acid and dopamine, to cross the blood brain barrier. We determined the tissue content of radioactivity in selected brain regions, in a short‐run study design, following injections of [3H]N‐oleoyl‐dopamine (0.4 µCi) into the internal carotid artery in the rat. These results were compared with intracarotid injections of [3H]dopamine and with intravenous injections of both radiolabeled compounds. The level of radioactivity was determined using liquid scintillation and was expressed as the percentage of its total dose injected per gram of tissue. We found that the 15‐min brain uptake of radioactivity, with no distinct regional variations, amounted to about 6% following the intracarotid [3H]N‐oleoyl‐dopamine, which was a significant 3–4‐fold increase over that following similar administration of [3H]dopamine. Intravenous injections of [3H]N‐oleoyl‐dopamine gave a much smaller yield of radioactivity in brain tissue samples which was still severalfold greater than that for intravenous [3H]dopamine. Qualitative thin‐layered chromatography screening showed the presence of unchanged N‐oleoyl‐dopamine in the brain following injections. We conclude that N‐oleoyl‐dopamine has an appreciable ability to cross the blood‐brain barrier, which contrasts the limited transfer of dopamine alone. N‐oleoyl‐dopamine might exert physiological effects due to its known affinity for the central vanilloid receptors or to better satisfying the brain tissue demand for dopamine. The study suggests a potential pharmacological role for N‐oleoyl‐dopamine delivered exogenously in helping regulate the brain function. Drug Dev. Res. 60:217–224, 2003. © 2003 Wiley‐Liss, Inc. 相似文献
60.
Calorie restriction in nonhuman primates: mechanisms of reduced morbidity and mortality 总被引:1,自引:0,他引:1
Long term chronic calorie restriction (CR) of adult nonhuman primates
significantly reduces morbidity and increases median age of death. The
present review is focused upon an ongoing study of sustained adult- onset
calorie restriction, which has been underway for 15 years. Monkeys,
initially calorie restricted at about 10 years of age, are now
approximately 25 years old. The median life span of these restricted
monkeys is increasing, now exceeding that of ad libitum (AL)-fed monkeys.
In our laboratory, maximum life span for AL-fed monkeys appears to be about
40 years. Thus, whether CR can also increase maximal life span, as it does
in rodents, cannot be determined for at least another 15 years. The
earliest detectable positive benefit on morbidity in these monkeys was
previously reported as the prevention of obesity. Current evidence, as
reviewed here, suggests that much obesity- associated morbidity is also
mitigated by sustained calorie restraint in nonhuman primates. Furthermore,
probably because of the prevention of obesity, diabetes has also been
prevented. Recent findings include the identification of extraordinary
changes in the glycogen synthesis pathway, and on the phosphorylation of
glycogen synthase in response to insulin. This calorie restriction-induced
prevention of morbidity does not require excessive leanness, but is clearly
present when body fat is within the normal range of 10 to 22%, and this is
likely to be true in humans as well.
相似文献