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991.
Brian R Lawson Stanley M Belkowski John F Whitesides Paul Davis John W Lawson 《BMC complementary and alternative medicine》2007,7(1):20
Background
Rheumatoid arthritis (RA) and its accepted animal model, murine collagen-induced arthritis (CIA), are classic autoimmune inflammatory diseases which require proinflammatory cytokine production for pathogenesis. We and others have previously used N, N-dimethylglycine (DMG) and extracts from the New Zealand green-lipped mussel Perna canaliculus (Perna) as potent immunomodulators to modify ongoing immune and/or inflammatory responses. 相似文献992.
Antitumor immune response by CX3CL1 fractalkine gene transfer depends on both NK and T cells 总被引:6,自引:0,他引:6
Xin H Kikuchi T Andarini S Ohkouchi S Suzuki T Nukiwa T Huqun Hagiwara K Honjo T Saijo Y 《European journal of immunology》2005,35(5):1371-1380
The CX3C chemokine fractalkine (CX3CL1) exists as both a membrane-bound form promoting firm cell-cell adhesion and a soluble form chemoattracting leukocytes expressing its receptor CX3CR1. When adenoviral vector expressing mouse fractalkine (AdFKN) was transduced to the tumor cells, fractalkine was expressed as both membrane-bound form on the tumor cells and soluble form in the supernatant in vitro. Intratumoral injection of AdFKN (1 x 10(9)PFU/tumor) into C26 and B16F10 tumors resulted in marked reduction of tumor growth compared to control (C26: 86.5%, p<0.001; B16F10: 85.5%, p<0.001). Histological examination of tumor tissues revealed abundant infiltration of NK cells, dendritic cells, and CD8(+) T lymphocytes 3 and/or 6 days after treatment with AdFKN. Splenocytes from mice treated by AdFKN developed tumor-specific cytotoxic T cells, and thereby protected from rechallenging with parental tumor cells. Antitumor effects by AdFKN were completely abrogated in both NK cell-depleted mice and CD8(-/-) mice, and partially blocked in CD4(-/-) mice. These data indicated that fractalkine mediates antitumor effects by both NK cell-dependent and T cell-dependent mechanisms. This study suggests that fractalkine can be a suitable candidate for immunogene therapy of cancer because fractalkine induces both innate and adaptive immunity. 相似文献
993.
Patrick Tan 《BMC medicine》2008,6(1):27
Identifying the complete repertoire of genes and genetic variants that regulate the pathogenesis and progression of human
disease is a central goal of post-genomic biomedical research. In cancer, recent studies have shown that genome-wide association
studies can be successfully used to identify germline polymorphisms associated with an individual's susceptibility to malignancy.
In parallel to these reports, substantial work has also shown that patterns of somatic alterations in human tumors can be
successfully employed to predict disease prognosis and treatment response. A paper by Van Ness et al. published this month
in BMC Medicine reports the initial results of a multi-institutional consortium for multiple myeloma designed to evaluate the role of germline
polymorphisms in influencing multiple myeloma clinical outcome. Applying a custom-designed single nucleotide polymorphism
microarray to two separate patient cohorts, the investigators successfully identified specific combinations of germline polymorphisms
significantly associated with early clinical relapse. These results raise the exciting possibility that besides somatically
acquired alterations, germline genetic background may also exert an important influence on cancer patient prognosis and outcome.
Future 'personalized medicine' strategies for cancer may thus require incorporating genomic information from both tumor cells
and the non-malignant patient genome. 相似文献
994.
Pacemaker frequency is increased by sodium nitroprusside in the guinea pig gastric antrum 总被引:2,自引:1,他引:2
The basis of rhythmic activity observed at the dorsal column nuclei (DCN) is still open to debate. This study has investigated the electrophysiological properties of isolated DCN neurones deprived of any synaptic influence, using the perforated-patch technique. About half of the DCN neurones (64/130) were spontaneously active. More than half of the spontaneous neurones (36/64) showed a low threshold membrane oscillation (LTO) with a mean frequency of 11.4 Hz (range: 4.3–22.1 Hz, n = 20; I = 0). Cells showing LTOs also invariably showed a rhythmic 1.2 Hz clustering activity (groups of 2–5 action potentials separated by silent LTO periods). Also, more than one-third of the silent neurones presented clustering activity, always accompanied by LTOs, when slightly depolarised. The frequency of LTOs was voltage dependent and could be abolished by TTX (0.5 μM) and riluzole (30 μM), suggesting the participation of a sodium current. LTOs were also abolished by TEA (15 mM), which transformed clustering into tonic activity. In voltage clamp, most DCN neurones (85 %) showed a TTX-/riluzole-sensitive persistent sodium current ( I Na,p ), which activated at about -60 mV and had a half-maximum activation at −49.8 mV. An M-like, non-inactivating outward current was present in 95 % of DCN neurones, and TEA (15 mM) inhibited this current by 73.7 %. The non-inactivating outward current was also inhibited by barium (1 mM) and linopirdine (10 μM), which suggests its M-like nature; both drugs failed to block the LTOs, but induced a reduction in their frequency by 56 and 20 %, respectively. These results demonstrate for the first time that DCN neurones have a complex and intrinsically driven clustering discharge pattern, accompanied by subthreshold membrane oscillations. Subthreshold oscillations rely on the interplay of a persistent sodium current and a non-inactivating TEA-sensitive outward current. 相似文献
995.
Charcot-Marie-Tooth disease (CMT) is a heterogeneous disorder and is traditionally classified into two major types, CMT type 1 (CMT1) and CMT type 2 (CMT2). Most CMT1 patients are associated with the duplication of 17p11.2-p12 (CMT1A duplication) and small numbers of patients have mutations of the peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ), connexin 32 (Cx32/GJB1), and early growth response 2 (EGR2) genes. Some mutations of MPZ and Cx32 were also associated with the clinical CMT2 phenotype. We constructed denaturing gradient gel electrophoresis (DGGE) analysis as a screening method for PMP22, MPZ, and Cx32 mutations and studied 161 CMT patients without CMT1A duplication. We detected 27 mutations of three genes including 15 novel mutations; six of PMP22, three of MPZ, and six of Cx32. We finally identified 21 causative mutations in 22 unrelated patients and five polymorphic mutations. Eighteen of 22 patients carrying PMP22, MPZ, or Cx32 mutations presented with CMT1 and four of them with MPZ or Cx32 mutations presented with the CMT2 phenotype. DGGE analysis was sensitive for screening for those gene mutations, but causative gene mutation was not identified in many of the Japanese patients with CMT, especially with CMT1. Other candidate genes should be studied to elucidate the genetic basis of Japanese CMT patients. 相似文献
996.
Mohammad A. Karim Koji Suzuki Kazuyoshi Fukai Jangsuk Oh Deborah L. Nagle Karen J. Moore Ernest Barbosa Tzipora Falik‐Borenstein Alexandra Filipovich Yasushi Ishida Sirpa Kivrikko Christoph Klein Friedmar Kreuz Alex Levin Hiroaki Miyajima Jose R. Regueiro Carolyn Russo Eiichiro Uyama Outi Vierimaa Richard A. Spritz 《American journal of medical genetics. Part A》2002,108(1):16-22
Chediak‐Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by severe immunologic defects, reduced pigmentation, bleeding tendency, and progressive neurological dysfunction. Most patients present in early childhood and die unless treated by bone marrow transplantation. About 10–15% of patients exhibit a much milder clinical phenotype and survive to adulthood, but develop progressive and often fatal neurological dysfunction. Very rare patients exhibit an intermediate adolescent CHS phenotype, presenting with severe infections in early childhood, but a milder course by adolescence, with no accelerated phase. Here, we describe the organization and genomic DNA sequence of the CHS1 gene and mutation analysis of 21 unrelated patients with the childhood, adolescent, and adult forms of CHS. In patients with severe childhood CHS, we found only functionally null mutant CHS1 alleles, whereas in patients with the adolescent and adult forms of CHS we also found missense mutant alleles that likely encode CHS1 polypeptides with partial function. Together, these results suggest an allelic genotype–phenotype relationship among the various clinical forms of CHS. © 2002 Wiley‐Liss, Inc. 相似文献
997.
When a saccade occurs to an interesting object, visual fixation holds its image on the fovea and suppresses saccades to other objects. Electrical stimulation of the frontal eye field (FEF) has been reported to elicit saccades, and recently also to suppress saccades. This study was performed to characterize properties of the suppression of visually guided (Vsacs) and memory-guided saccades (Msacs) induced by electrical stimulation of the FEF in trained monkeys. For any given stimulation site, we determined the threshold for electrically evoked saccades (Esacs) at < or =50 microA and then examined suppressive effects of stimulation at the same site on Vsacs and Msacs. FEF stimulation suppressed the initiation of both Vsacs and Msacs during and about 50 ms after stimulation at stimulus intensities lower than those for eliciting Esacs, but did not affect the vector of these saccades. Suppression occurred for ipsiversive but not contraversive saccades, and more strongly for saccades with larger amplitudes and those with initial eye positions shifted more in the saccadic direction. The most effective stimulation timing for suppression was about 50 ms before saccade onset, which suggests that suppression occurred in the efferent pathway for generating Vsacs at the premotor rather than the motoneuronal level, most probably in the superior colliculus and/or the paramedian pontine reticular formation. Suppression sites of ipsilateral saccades were distributed over the classical FEF where saccade-related movement neurons were observed. The results suggest that the FEF may play roles in not only generating contraversive saccades but also maintaining visual fixation by suppressing ipsiversive saccades. 相似文献
998.
Tanimoto Y Hayakawa T Nemoto K 《Journal of biomedical materials research. Part B, Applied biomaterials》2005,72(2):310-315
The aim of this study was to investigate the extent of polymerization (Ep) in terms of polymerization rate of UDMA/TEGDMA resin mixtures and its composite resin, by using a differential scanning calorimeter (DSC) technique employing a photopolymerization apparatus. The resin mixtures used in this study consisted of urethane dimethacrylate (UDMA) as a base monomer and triethyleneglycol dimethacrylate (TEGDMA) as a low viscosity monomer. The concentration of TEGDMA in the mixed monomer was varied to 0, 20, 40, 60, 80, and 100 mol %. Additionally, using a base monomer consisting of 60 mol % UDMA and 40 mol % TEGDMA, four kinds of composites with silica filler of 0, 20, 40, 60, and 70 wt %, were prepared in this study. The general reaction profile and Ep values were obtained from the DSC curves. Increasing the concentration of TEGDMA resulted in a decrease in the viscosity of the UDMA/TEGDMA mixture, a delay in the time to maximum polymerization rate, and an increase in the Ep values of the resin mixtures. Furthermore, Ep values decreased with increasing filler content between 0 and 60 wt % but did not decrease further between 60 and 70 wt %. 相似文献
999.
We have known for some time that the epidemiology of human stroke is sexually dimorphic until late in life, well beyond the
years of reproductive senescence and menopause. Now, a new concept is emerging: the mechanisms and outcome of cerebral ischemic injury are influenced strongly by biological sex as well as the availability of sex steroids to the
brain. The principal mammalian estrogen (17 β estradiol or E2) is neuroprotective in many types of brain injury and has been
the major focus of investigation over the past several decades. However, it is becoming increasingly clear that although hormones
are a major contributor to sex-specific outcomes, they do not fully account for sex-specific responses to cerebral ischemia.
The purpose of this review is to highlight recent studies in cell culture and animal models that suggest that genetic sex
determines experimental stroke outcome and that divergent cell death pathways are activated after an ischemic insult. These
sex differences need to be identified if we are to develop efficacious neuroprotective agents for use in stroke patients. 相似文献
1000.
Cloning of a truncated Babesia equi gene encoding an 82-kilodalton protein and its potential use in an enzyme-linked immunosorbent assay 下载免费PDF全文
Hirata H Ikadai H Yokoyama N Xuan X Fujisaki K Suzuki N Mikami T Igarashi I 《Journal of clinical microbiology》2002,40(4):1470-1474
To isolate Babesia equi genes encoding immunodominant proteins, a cDNA expression library prepared from B. equi mRNA was immunoscreened with B. equi-infected horse serum. Eighteen positive cDNA clones were obtained, and the clone that showed the strongest immunoreactivity, designated Be82, was further characterized. The Be82 gene consisted of 1,953 bp and contained a partial open reading frame lacking the 5'-terminal sequence. As shown by Western blot analyses, immune sera from mice intraperitoneally injected with the Be82 gene product recognized the 82- and 52-kDa proteins of B. equi but not those of Babesia caballi. The glutathione S-transferase fusion protein expressed in Escherichia coli that was purified and used as the antigen in the enzyme-linked immunosorbent assay reacted specifically with B. equi-infected horse sera. These results suggest that the Be82 gene product is a potential diagnostic antigen candidate in the detection of B. equi infection in horses that will be useful both in the performance of epidemiological studies and in the granting of quarantine passes. 相似文献