Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With a view to developing improved mucosal immunisation strategies, we have quantitatively investigated the uptake of fluorescent polystyrene carboxylate microspheres (1.1 microm diameter), using histology and fluorescence-activated cell sorting, following intranasal delivery to BALB/c mice. To qualify these biodistribution data, antigen specific memory and effector responses in the spleens of mice immunised nasally with Yersinia pestis V antigen loaded poly(lactide) (PLA) microspheres (1.5 microm diameter) were assessed at 4, 7 and 11 days. Irrespective of administration vehicle volume (10 or 50 microl), appreciable numbers of fluorescent microspheres were detected within nasal associated lymphoid tissues (NALT) and draining cervical lymph nodes. Nasal administration of the particles suspended in 50 microl volumes of phosphate-buffered saline (PBS) served to deposit the fluorescent microspheres throughout the respiratory tract (P<0.05). In these animals, appreciable particle uptake into the mediastinal lymph node was noted (P<0.05). Also, spleens removed from mice 10 days after fluorescent particle application contained significantly more microspheres if the suspension had been nasally instilled using a 50 microl volume (P<0.05). Appreciable memory (and effector from day 7) responses were detected in mediastinal lymph nodes removed from mice immunised nasally with 50 microl volumes of microparticulated or soluble V antigen. Immunological responses in splenic tissue removed 7 days after intranasal immunisation corroborated the thesis that the spleen can act as an inductive site following bronchopulmonary deposition of particulated antigen: upon exposure to V in vitro, splenic T-cells from mice nasally immunised with 50 microl volumes of microspheres incorporated statistically greater (P<0.05) quantities of [3H]thymidine into newly synthesised DNA than did T-cells from cohorts nasally immunised with 50 microl volumes of V in solution. Similarly, significant numbers of anti-V IgG secreting cells were only detected in spleens from mice immunised intramuscularly or nasally with microparticles. These immunological and biodistribution data support the tenet that, following an appropriate method of mucosal delivery, microparticles can translocate to tissues in the systemic compartment of the immune system and thence provoke immunological reactions therein.
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PMID:Microsphere translocation and immunopotentiation in systemic tissues following intranasal administration. 1153 24

Substance P (SP) is a neuropeptide associated with sensory innervation of lymphoid tissue and a suspected modulator of lymphatic function in inflammation. Only a few studies have examined the effects of SP on lymphatic contraction, and it is not clear to what extent SP acts directly on the lymphatic muscle and/or endothelium or indirectly through changes in intraluminal filling pressure secondary to increases in capillary permeability/filtration. We tested the effects of SP on the spontaneous contractions of rat isolated mesenteric lymphatic vessels under isometric and isobaric conditions, hypothesizing that low concentrations would stimulate lymphatic pumping by enhancing lymphatic muscle contraction in a manner complementary to the effect of increased preload. Under isometric conditions, SP (10 nM) dramatically enhanced lymphatic chronotropy and inotropy. Unlike guinea pig lymphatics, SP actions were not blocked by cyclooxygenase or PLA(2) inhibition. In the absence of SP, ramp increases in isometric preload resulted in x approximately 1.6 increases in contraction amplitude (Amp) and x approximately 1.7 increases in frequency (Freq). SP increased Freq by x approximately 2.4, Amp by x approximately 1.9, and the Amp-Freq product (AFP) by x approximately 3.5. Under isobaric conditions, the pressure elevation from 0.5 to 10 cmH(2)O in the absence of SP decreased Amp by x approximately 0.6 and increased Freq by x approximately 1.8. SP caused a modest increase in Amp, a robust increase in Freq at all pressures, and shifted the AFP-pressure relationship upward and leftward. Therefore, SP has substantial positive inotropic and chronotropic effects on rat lymphatic muscle, improving pump efficiency independent of the effects of preload and broadening of the working range of the lymphatic pump.
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PMID:Modulation of lymphatic muscle contractility by the neuropeptide substance P. 1853 52

The skin represents one of the tissues that are most profoundly influenced by alterations in the quality of lipids (lipoquality). Lipids not only constitute cellular membranes, but also serve as bioactive lipid mediators and essential components of the skin barrier. Phospholipase A2 (PLA2) enzymes supply fatty acids and lysophospholipids from membrane phospholipids, thereby variably affecting cutaneous homeostasis. Accordingly, perturbation of particular PLA2-driven lipid pathways can be linked to various forms of skin disease. In this review article, we highlight the roles of several PLA2 subtypes in cutaneous pathophysiology, as revealed by transgenic/knockout studies in combination with comprehensive lipidomics. We focus mainly on secreted PLA2 group IIF (sPLA2-IIF), which is associated with epidermal hyperplasia through mobilization of a unique lipid metabolite. We also address the distinct roles of sPLA2-IIE in hair follicles and sPLA2-IID in lymphoid immune cells that secondarily affect cutaneous inflammation, and provide some insights into species differences in sPLA2s. Additionally, we briefly overview the patatin-like phospholipase PNPLA1, which belongs to the Ca2+-independent PLA2 (iPLA2) family, as a key regulator of skin barrier function through catalysis of a unique non-PLA2 reaction. These knowledges on lipid metabolism driven by various PLA2 subtypes will open novel opportunities for translated studies toward diagnosis and therapy of human skin diseases.
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PMID:Phospholipase A2 in skin biology: new insights from gene-manipulated mice and lipidomics. 3054 11

This paper aims to observe and analyze the safety and clinical efficacy of Fingolimod combined with alteplase intravenous thrombolysis in the treatment of acute ischemic stroke. 90 patients with acute ischemic stroke were randomly divided into two groups. 45 patients in the control group were given alteplase intravenous thrombolysis for injection. 45 cases in the trial group were treated with Fingolimod combined with alteplase. There was no significant difference in NIHSS score, mRS score and BI index between the two groups 14 days after treatment, but 90 days after treatment, NIHSS score and mRS score of the experimental group were significantly lower than that of the control group, and BI index was significantly higher (P<0.05). 24 hours after oral administration of Fingolimod (0.5 mg), the circulating blood CD4 + T, CD8 + T, CD19 + B and CD56 + natural killer cells of the patients in the combined treatment group decreased steadily to varying degrees. The results confirm the pharmacological effect of Fingolimod: it changes lymphocyte migration, promotes lymphocyte to enter lymphoid tissue, prevents lymphocyte from leaving lymphoid tissue to enter the peripheral circulation, and thus prevents these immune cells from infiltrating the central nervous system. The results showed that Fingolimod combined with alteplase intravenous thrombolysis is safe for patients with acute ischemic stroke. .
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PMID:Efficacy of fingolimod combined with alteplase in acute ischemic stroke and rehabilitation nursing. 3085 78


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