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101.
102.
Tristan Barnes Preston Parry Iris Hart Carol Jones Michele Minet David Patterson 《Somatic Cell and Molecular Genetics》1993,19(4):405-411
De novo UMP synthesis is a critical metabolic pathway for nucleic acid synthesis and for a variety of metabolic pathways. The pathway is a target for many widely used cancer chemotherapy agents, several of which are pyrimidine analogs. Humans and cattle have been described with mutations in UMP synthesis that lead to serious inborn errors of metabolism. Dihydroorotate dehydrogenase (EC 1.3.3.1) (DHODH) carries out the fourth committed step in the pathway and may also be important for mitochondrial electron transport and oxygen radical metabolism. We report here that the gene encoding this enzyme in humans is located in the chromosomal region 16q22. With the mapping of DHODH, the mapping of all the steps of UMP synthesis is complete. All three genes involved map to different human chromosomes. This information is important in consideration of regulation of UMP synthesis in mammals, including humans. 相似文献
103.
Anticipatory control of hand and eye movements in humans during oculo-manual tracking 总被引:2,自引:0,他引:2
Anticipatory activity of hand and eye has been examined during oculo-manual tracking of a constant velocity visual target with a hand cursor. Both target and cursor were presented briefly (< 480 ms), but repeatedly, at regular inter-stimulus intervals (ISI). In Expt 1, the build-up of hand and eye responses was examined for target velocities varying from 10–40 deg s−1 with an ISI of 2.4 s. The velocity 100 ms after target onset (i.e. prior to visual feedback) for both hand and eye ( V 100 ) progressively increased over the first four presentations but then attained a steady state (SS). SS V 100 values for eye and hand increased in proportion to target velocity and were thus predictive of forthcoming movement. Hand velocity exceeded eye velocity but both exhibited similar anticipatory trajectories. In Expt 2, target velocity was constant (40 deg s−1 ) but ISI varied from 0.48–3.74 s. Subjects made anticipatory eye movements for all ISIs but hand movements were often reactive at the longest ISI. If the target failed to appear as expected, subjects initiated predictive hand and eye responses with timing appropriate for the prevailing ISI. In Expt 3, predictive responses were compared with responses to randomised presentation. Peak hand velocity was greater in the randomised mode than in the predictive condition, whereas the converse was true for peak eye velocity. This difference is discussed in terms of the mechanisms of positional error correction in hand and eye. Results provide evidence of similar anticipatory mechanisms in hand and eye, using storage of velocity and timing to achieve rapid prediction of target motion. 相似文献
104.
M B Krockenberger P J Canfield J Barnes L Vogelnest J Connolly C Ley R Malik 《Medical mycology》2002,40(3):273-282
Cryptococcus neoformans var. gattii has been shown to have a strong association with eucalypts frequently used by koalas and, not surprisingly, it has been shown to colonize the nasal cavities of koalas. The progression from nasal colonization to tissue invasion is critical to understanding the pathogenesis of cryptococcosis in this species and provides a model for pathogenesis of cryptococcosis in other species. Cryptococcal antigenaemia was detected in twenty-eight healthy koalas from three different regions. This was interpreted as representing limited subclinical disease. One koala developed cryptococcal pneumonia 6 months after leaving the study, whereas another developed cryptococcal meningoencephalitis during the course of the study. Opportunistic necropsies on ten antigen-positive koalas resulted in discovery of small cryptococcal lesions in two (paranasal sinus and lung, respectively). Our data suggest that cryptococcal antigenaemia occurs commonly in koalas, especially in areas with a high environmental presence of C n. var. gattii. Subclinical disease appears most likely to manifest as a small focal lesion in the respiratory tract. Possible outcomes include elimination by an effective immune response, quiescence with possibility of later re-activation or direct progression to overt disease. Symptomatic and subclinical cases showed differences in levels of antigenaemia. The data presented have significant implications for koalas in captivity. 相似文献
105.
The effect of extracellular pH (pHe 6.9–8.1) and intracellular pH (pHi 6.4–8.1) on the non-inactivating voltage-sensitive M-like potassium current (IKx) was studied in patch-clamped salamander rod photoreceptors. The midpoint of the IKx activation curve shifted by 6.6 mV per pHe unit, with acidification producing positive shifts and alkalinization producing negative shifts. The time constant of IKx activation shifted with pHe in a manner consistent with the shifts in the activation curve. Maximum conductance and gating charge were unaffected by changes in pHe. IKx did not depend on pHi. Given the importance of IKx in rod function, these results suggest that pHe could affect the signal transmitted from rods by changing IKx activation parameters. 相似文献
106.
Ricciardolo FL Caramori G Ito K Capelli A Brun P Abatangelo G Papi A Chung KF Adcock I Barnes PJ Donner CF Rossi A Di Stefano A 《The Journal of allergy and clinical immunology》2005,116(5):1028-1035
BACKGROUND: Reactive nitrogen species, formed via the reaction of nitric oxide (NO) with superoxide anion and via (myelo)peroxidase-dependent oxidation of NO(2)(-), have potent proinflammatory and oxidizing actions. Reactive nitrogen species formation and nitrosative stress are potentially involved in chronic obstructive pulmonary disease (COPD) pathogenesis. OBJECTIVES: To investigate the expression of markers of nitrosative stress, including nitrotyrosine (NT), inducible NO synthase (iNOS), endothelial NO synthase (eNOS), myeloperoxidase (MPO), and xanthine oxidase (XO) in bronchial biopsies and bronchoalveolar lavage from patients with mild to severe stable COPD compared with control groups (smokers with normal lung function and nonsmokers). METHODS: The expression of NT, iNOS, eNOS, MPO and XO in the bronchial mucosa and bronchoalveolar lavage of patients was measured by using immunohistochemistry, Western blotting, and ELISA and correlated with the inflammatory cell profile. RESULTS: Patients with severe COPD in stable phase had higher numbers of NT(+) and MPO(+) cells in their bronchial submucosa compared with mild/moderate COPD, smokers with normal lung function, and nonsmokers (P < .01). iNOS(+) and eNOS(+) but not XO(+) cells were significantly increased in smokers with COPD or normal lung function compared with nonsmokers (P < .05 and P < .01, respectively). In patients with COPD, the number of MPO(+) cells was significantly correlated with the number of neutrophils (r = +0.61; P < .0025) in the bronchial submucosa. Furthermore, the number of NT(+) and MPO(+) cells was negatively correlated with postbronchodilator FEV(1). CONCLUSION: These data suggest that nitrosative stress, mainly mediated by MPO and neutrophilic inflammation, may contribute to the pathogenesis of severe COPD. 相似文献
107.
108.
Effect of topical capsaicin on the cutaneous responses to inflammatory mediators and to antigen in man 总被引:1,自引:0,他引:1
M T McCusker K F Chung N M Roberts P J Barnes 《The Journal of allergy and clinical immunology》1989,83(6):1118-1124
Topical capsaicin pretreatment is known to deplete cutaneous sensory nerves of neuropeptides. We have assessed the effect of topical capsaicin pretreatment on the responses to intradermal injections of histamine and platelet-activating factor (PAF) in six normal subjects, and of prostaglandin E2, histamine, and antigen in 10 atopic subjects. Capsaicin pretreatment caused significant inhibition of the immediate flare response to histamine in both normal (19.8 +/- 2.6 to 7.3 +/- 2.9 cm2 at 5 minutes; p less than 0.01) and atopic subjects (16.5 +/- 1.4 to 10.3 +/- 1.9 cm2 at 5 minutes; p less than 0.01). The PAF-induced flare was also inhibited from 12.2 +/- 2.9 to 2.7 +/- 1.6 cm2 at 5 minutes after injection (p less than 0.01). In contrast, capsaicin pretreatment did not significantly alter the flare responses to prostaglandin E2 or antigen in atopic subjects. The acute wheal responses to all stimuli were unchanged, as was the late-phase response to antigen. These results support the hypothesis that the cutaneous vasodilator effect of histamine and PAF may be mediated by a local axon reflex involving the release of neuropeptides from sensory nerves. A consistent effect of capsaicin pretreatment on the flare response induced by endogenous mediators released during a cutaneous IgE-mediated response was not observed. Increases in microvascular permeability and the late-phase response to antigen are independent of neuropeptide release from cutaneous nerves. 相似文献
109.
Kennedy LJ Carter SD Barnes A Bell S Bennett D Ollier B Thomson W 《Tissue antigens》1999,53(2):184-189
To date, DNA sequences for 29 dog DLA-DRB1 alleles have been reported. However, no data exists on the frequencies of these alleles within the general dog population, nor is there any indication of whether there is interbreed variation of allele distribution. We have addressed this by establishing a molecular based sequence-specific oligonucleotide probing (SSOP) method to identify all of the known broad DRB1 types and we have used this to type a random panel of dogs. A series of oligonucleotide probes were designed to detect known polymorphisms in the three DRB1 hypervariable regions, together with two distinctive motifs in other regions of exon 2. This set of probes enabled us to assign broad DRB1 types. Two hundred and eighteen dogs were SSOP typed for DRB1. All but 4 of the published DLA-DRB1 alleles were identified in these animals. Interbreed variation in both allele distributions and allele frequencies were observed, which may be useful in the study of genetic variation between breeds. This variation also has implications for the selection of control groups for studies aimed at identifying MHC associations with disease susceptibility in the dog. 相似文献
110.
Protective cytotoxic T lymphocyte responses against paramyxoviruses induced by epitope-based DNA vaccines: involvement of IFN-gamma 总被引:1,自引:0,他引:1
Hsu SC; Obeid OE; Collins M; Iqbal M; Chargelegue D; Steward MW 《International immunology》1998,10(10):1441-1447
Plasmid DNA vectors have been constructed with minigenes encoding a single
cytotoxic T lymphocyte (CTL) epitope from either the M2 protein of
respiratory syncytial virus (RSV) or from the nucleoprotein of measles
virus (MV) with or without a signal sequence (also called secretory or
leader sequence). Following intradermal immunization, plasmids in which the
CTL epitopes were expressed in-frame with the signal sequence were more
effective at inducing peptide- and virus- specific CTL responses than
plasmids expressing CTL epitopes without the signal sequence. This
immunization resulted in protection against MV-induced encephalitis and a
significant reduction in viral load following RSV challenge. The reduction
of viral load following RSV challenge was abrogated by prior injection with
anti-IFN-gamma antibodies. These results highlight the ability of
epitope-based DNA immunization to induce protective immune responses to
well-defined epitopes and indicate the potential of this approach for the
development of vaccines against infectious diseases.
相似文献