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961.
1. Whether bradykinin (BK), which is known as an endogenous pain-producing substance, induces augmentation of the discharges of polymodal receptors evoked by heat stimulation was investigated in in vitro canine testis-superior spermatic nerve preparations. 2. The heat response was significantly augmented by pretreatments with BK at concentrations greater than 0.094 nM, whereas BK induced significant increases in the mean discharge rates at concentrations above 9.4 nM. Both effects increased in a concentration-dependent manner. The augmenting effect of BK on the heat response diminished within 10 min after application of BK, regardless of concentration. 3. When 9.4 nM BK was applied in a mixture with 940 nM NPC349, a B2 receptor antagonist, the averaged mean discharge rate evoked by BK and the averaged augmenting effect were both significantly suppressed compared with those induced by BK given alone. 4. The augmenting effect of BK on the heat response of polymodal receptors could be observed even in the absence of BK-evoked discharges per se in several cases in which low concentrations of BK or BK plus B2 antagonists were given. 5. These findings suggest that the augmenting effects of BK on the heat response depend on B2 receptor-mediated intracellular processes acting in parallel to, but not directly on, the impulse-generation mechanism of the heat response of the polymodal receptor. 相似文献
962.
963.
964.
H Imoto Y Sakamura K Ohkouchi R Atsumi Y Takakura H Sezaki M Hashida 《Cancer research》1992,52(16):4396-4401
Disposition characteristics of model macromolecules with different physicochemical characteristics and macromolecular prodrugs of mitomycin C, namely mitomycin C-dextran conjugates, were studied in tissue-isolated tumor preparations of Walker 256 carcinoma with the use of a single-pass vascular perfusion technique. In constant infusion experiments, all radiolabeled macromolecules accumulated in the tumor tissue, but the degree and pattern of distribution greatly varied, depending on their electric charges. Positively charged macromolecules were markedly accumulated compared with those that were neutral or negatively charged. In addition, their concentrations were significantly higher in viable than in necrotic regions, while neutral and negative compounds were distributed in necrotic rather than in viable regions. Pharmacokinetic analysis of tissue concentration-time courses of positively charged diethylaminoethyl and neutral dextrans showed that their movement occurred by convective fluid flow, and that high tissue accumulation of positively charged macromolecules could be explained by strong binding due to electrostatic interaction. For neutral and anionic macromolecules with negligible affinity to the tissue, it was suggested that the final concentration gradient between the viable and necrotic regions was decided by their tissue fluid content. Thus, the present study revealed the basic disposition characteristics of macromolecules in tumor tissue relative to their physicochemical properties. 相似文献
965.
A lipopolysaccharide (LPS)-resistant mutant isolated from a macrophagelike cell line, J774.1, exhibits an altered activated-macrophage phenotype in response to LPS.
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A bacterial lipopolysaccharide (LPS)-resistant mutant was isolated from murine macrophagelike cell line J774.1. The mutant showed selective resistance to LPS and lipid A and was almost 10(5)- to 10(6)-fold more resistant than the parent; it grew even in the presence of 1 mg of Escherichia coli O55:B5 LPS per liter, whereas the parent did not grow with less than 10 ng of LPS per milliliter. We next examined the mutant for activation of various functions of macrophages on LPS treatment. This LPS-resistant mutant secreted interleukin-1 and tumor necrosis factor almost as effectively as the parent did. The mutant cells also changed transiently from a round to a spread form; however, they became round again afterwards. The mutant cells secreted less arachidonic acid in response to LPS. These results also suggest that this LPS-resistant mutant responds to LPS and shows activation of some macrophage functions. However, this mutant did not exhibit elevation of O2- generation or H2O2 generation after LPS treatment. Also, treatment of the mutant cells with murine recombinant gamma interferon was partly able to correct the defect in O(2-)-generating activity in response to LPS, suggesting that this defect is probably due to some of the LPS signal pathways. This implies that there is some correlation between O2- metabolism in LPS-activated macrophages and decreases in cell growth and viability. 相似文献
966.
T Y Nakagawa H Von Grafenstein J E Sears J Williams C A Janeway R A Flavell 《European journal of immunology》1991,21(11):2851-2855
CD4+ T cells recognize processed exogenous antigen in the form of peptides bound to syngeneic major histocompatibility complex class II molecules on antigen-presenting cells. We have developed a novel and convenient method to synthesize and map CD4+ T cell epitopes of cloned antigens using polymerase chain reaction (PCR)-directed construction of genes expressing recombinant protein fragments. Unique restriction sites incorporated into the PCR primers were employed for the unidirectional cloning of gene fragments into a bacterial expression vector that can be induced to high-level expression. The bacterial lysate could be used directly in T cell proliferation assays. Overlapping recombinant fragments spanning the entire protein were generated and tested. The length of the sequence containing the epitope was further reduced by utilizing PCR to generate 3' truncations. Finally, a small number of overlapping peptides spanning a sequence of 39 amino acids were synthesized to identify a thirteen-amino acid peptide epitope within chicken transferrin that stimulates the T helper cell clone D10.G4.1. PCR-directed construction of fragments of antigen allows for optimal design of strategies for the mapping and analysis of CD4+ T cell epitopes. 相似文献
967.
Antibody-dependent cellular cytotoxicity (ADCC) activity against pseudorabies virus-infected target cells has been found to be lower in young pig peripheral blood leukocytes (PBLs) than in adults. Experiments were designed to investigate the reason(s) for low activity in the young, which are more at risk of fatal infection than adults. The percentage of polymorphonuclear leukocytes (PMNs), the major ADCC effector cell, in the whole leukocyte population did not have a bearing on the deficiency. Enrichment for PMNs did not alleviate differences in activity between young and adult pigs. Additionally, no suppressor cell(s) or factor(s) could be demonstrated to account for the ADCC deficiency. The source of the ADCC deficiency in the young was found to be related to the decreased ability of young pig effector cells to bind antibody-sensitized targets. This deficiency relative to adults was associated with decreased antibody binding to high affinity Fc receptors on young pig neutrophils. 相似文献
968.
Z-Y Sun J Wei L Xie Y Shen S-Z Liu G-Z Ju J-P Shi Y-Q Yu X Zhang Q Xu G P Hemmings 《European psychiatry》2004,19(6):354-357
The present study was designed to detect three single nucleotide polymorphisms (SNPs) located on 22q11 that was thought as being of particularly importance for genetic research into schizophrenia. We recruited a total of 176 Chinese family trios of Han descent, consisting of mothers, fathers and affected offspring with schizophrenia for the genetic analysis. The transmission disequilibrium test (TDT) showed that of three SNPs, rs10314 in the 3'-untranslated region of the CLDN5 locus was associated with schizophrenia (chi(2) = 4.75, P = 0.029). The other two SNPs, rs1548359 present in the CDC45L locus centromeric of rs10314 and rs739371 in the 5'-flanking region of the CLDN5 locus, did not show such an association. The global chi-square (chi(2)) test showed that the 3-SNP haplotype system was not associated with schizophrenia although the 1-df test for individual haplotypes showed that the rs1548359(C)-rs10314(G)-rs739371(C) haplotype was excessively non-transmitted (chi(2) = 5.32, P = 0.02). Because the claudin proteins are a major component for barrier-forming tight junctions that could play a crucial role in response to changing natural, physiological and pathological conditions, the CLDN5 association with schizophrenia may be an important clue leading to look into a meeting point of genetic and environmental factors. 相似文献
969.
P Y Wang 《Biomaterials》1991,12(1):57-62
Sustained-release implants for insulin can be made by compressing a powder admixture with palmitic acid as the excipient. At less than 20%, insulin does not disperse uniformly in the admixture. The size distribution of the excipient particles obtained after grinding for 15 min does not affect the sustained release action. When tested in a 33 d period, an 1/8-size piece (approximately 25 mg) implant cut from a pellet disc containing 20% insulin which is 13 mm in diameter and 1.5 mm thick released 0.12-0.17 mg insulin/d in diabetic Wistar rats. The 1/8-size piece containing 20% insulin or a rod of similar weight with a diameter of 3 mm, which can be inserted by a trocar, was optimal for the implant to provide a service-life of 49 +/- 7 d. The service-life decreased with progressive reduction in implant size. The implant functioned just as well subcutaneously or intraperitoneally and was eroded subcutaneously by 33.6-53.1% in 33 d. The glycosylated haemoglobin contents of diabetic animals on implant therapy which had a blood glucose level of 4.7 +/- 2.5 mmol/l were in a range of 6.2-8.9% compared to the control value of greater than 13% with chronic hyperglycemia. The overall results indicated that the implant was a promising alternative to daily insulin injections. 相似文献
970.
There is compelling evidence that the etiology of Alzheimer’s disease (AD) involves characteristic amyloid-β (Aβ) deposition, oxidative stress, and anomalous metal–Aβ protein interaction. New studies have implicated redox active metals such as copper, iron, and zinc as key mediating factors in the pathophysiology of Alzheimer’s disease. There is also evidence that drugs with metal chelating properties could produce a significant reversal of amyloid-β plaque deposition in vitro and in vivo. This paper reviews current observations on the etiologic role of zinc in AD. We also discuss the interactions of zinc and copper with Aβ, a factor that purportedly facilitates disease processes. Finally, we review the protective role of zinc against Aβ cytotoxicity and hypothesize how the apparent effect of zinc on AD pathology may be paradoxical, The Zinc Paradox. Indeed, complex pathologic stressors inherent to the Alzheimer’s diseased brain dictate whether or not zinc will be neuroprotective or neurodegenerative. Further research on the zinc paradox in AD is needed in order to elucidate the exact role zinc plays in AD pathogenesis. 相似文献