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21.
A genetic linkage map for zebrafish: comparative analysis and localization of genes and expressed sequences 下载免费PDF全文
Gates MA Kim L Egan ES Cardozo T Sirotkin HI Dougan ST Lashkari D Abagyan R Schier AF Talbot WS 《Genome research》1999,9(4):334-347
Genetic screens in zebrafish (Danio rerio) have isolated mutations in hundreds of genes with essential functions. To facilitate the identification of candidate genes for these mutations, we have genetically mapped 104 genes and expressed sequence tags by scoring single-strand conformational polymorphisms in a panel of haploid siblings. To integrate this map with existing genetic maps, we also scored 275 previously mapped genes, microsatellites, and sequence-tagged sites in the same haploid panel. Systematic phylogenetic analysis defined likely mammalian orthologs of mapped zebrafish genes, and comparison of map positions in zebrafish and mammals identified significant conservation of synteny. This comparative analysis also identified pairs of zebrafish genes that appear to be orthologous to single mammalian genes, suggesting that these genes arose in a genome duplication that occurred in the teleost lineage after the divergence of fish and mammal ancestors. This comparative map analysis will be useful in predicting the locations of zebrafish genes from mammalian gene maps and in understanding the evolution of the vertebrate genome. 相似文献
22.
Liu JQ; Bai XF; Shi FD; Xiao BG; Li HL; Levi M; Mustafa M; Wahren B; Link H 《International immunology》1998,10(8):1139-1148
Induction of mucosal tolerance by inhalation of soluble peptides with
defined T cell epitopes is receiving much attention as a means of
specifically down-regulating pathogenic T cell reactivities in autoimmune
and allergic disorders. Experimental autoimmune encephalomyelitis (EAE)
induced in the Lewis rat by immunization with myelin basic protein (MBP)
and Freund's adjuvant (CFA) is mediated by CD4+ T cells specific for the
MBP amino acid sequences 68-86 and 87-99. To further define the principles
of nasal tolerance induction, we generated three different MBP peptides
(MBP 68-86, 87-99 and the non- encephalitogenic peptide 110-128), and
evaluated whether their nasal administration on day -11, -10, -9, -8 and -7
prior to immunization with guinea pig MBP (gp-MBP) + CFA confers protection
to Lewis rat EAE. Protection was achieved with the encephalitogenic
peptides MBP 68-86 and 87-99, MBP 68-86 being more potent, but not with MBP
110-128. Neither MBP 68-86 nor 87-99 at doses used conferred complete
protection to gp-MBP-induced EAE. In contrast, nasal administration of a
mixture of MBP 68-86 and 87-99 completely blocked gp-MBP-induced EAE even
at lower dosage compared to that being used for individual peptides. Rats
tolerized with MBP 68-86 + 87-99 nasally showed decreased T cell responses
to MBP reflected by lymphocyte proliferation and IFN-gamma ELISPOT assays.
Rats tolerized with MBP 68-86 + 87-99 also had abrogated MBP-reactive
IFN-gamma and tumor necrosis factor-alpha mRNA expression in lymph node
cells compared to rats receiving MBP 110-128 nasally, while similar low
levels of MBP-reactive transforming growth factor-beta and IL-4 mRNA
expressing cells were observed in the two groups. Nasal administration of
MBP 68-86 + 87-99 only slightly inhibited guinea pig spinal cord
homogenate-induced EAE, and passive transfer of spleen mononuclear cells
from MBP 68-86 + 87-99-tolerized rats did not protect naive rats from EAE.
Finally, we show that nasal administration of MBP 68-86 + 87-99 can reverse
ongoing EAE induced with gp-MBP, although higher doses are required
compared to the dosage needed for prevention. In conclusion, nasal
administration of encephalitogenic MBP peptides can induce antigen-specific
T cell tolerance and confer incomplete protection to gp-MBP-induced EAE,
and MBP 68-86 and 87-99 have synergistic effects. Non-regulatory mechanisms
are proposed to be responsible for tolerance development after nasal
peptide administration.
相似文献
23.
Characterization of a gene encoding survival motor neuron (SMN)-related protein, a constituent of the spliceosome complex 总被引:2,自引:3,他引:2
Talbot K; Miguel-Aliaga I; Mohaghegh P; Ponting CP; Davies KE 《Human molecular genetics》1998,7(13):2149-2156
Mutations in the gene encoding the Survival Motor Neuron (SMN) protein are
responsible for autosomal recessive proximal spinal muscular atrophy (SMA).
SMN orthologues have been identified in the nematode worm Caenorhabditis
elegans and the yeast Schizosaccharomyces pombe but, to date, no human
paralogues have been described. Here we describe identification and
characterization of an SMN-related protein (SMNrp) gene that encodes a
novel protein of 239 amino acids, which has recently been identified as a
constituent of the spliceosome complex and designated SPF30. Significant
similarity to the SMN protein is apparent only within a central region of
SMNrp that represents a tudor domain. The SMNrp/SPF30 gene has been mapped
to chromosome 10q23. It is differentially expressed, with abundant levels
in skeletal muscle. An exclusively nuclear localization for SMNrp in
cultured cells and muscle sections was revealed using GFP fusion constructs
and thereafter confirmed with a polyclonal antibody raised against SMNrp.
Overexpression of SMNrp as a fusion protein in HeLa cells in culture
induced dose-dependent apoptosis with positive TUNEL staining. In addition
to a possible role for this protein as a pro-apoptotic factor, SMN and its
related protein share significant similarities in sequence and cellular
function.
相似文献
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A case of signet-ring cell lymphoma affecting bone marrow is reported. The tumour presented as multiple lytic lesions in the lumbosacral spine. A bone biopsy specimen showed the typical appearances of signet-ring cell lymphoma, and the cells stained positively with antiserum to CD20, though neither immunoglobulin light or heavy chains could be shown within the vacuoles. The patient subsequently responded to chemotherapy. 相似文献
27.
Balanos GM Talbot NP Robbins PA Dorrington KL 《Pflügers Archiv : European journal of physiology》2005,450(6):372-380
In healthy humans, changes in cardiac output are commonly accommodated with minimal change in pulmonary artery pressure. Conversely, exposure to hypoxia is associated with substantial increases in pulmonary artery pressure. In this study we used non-invasive measurement of an index of pulmonary artery pressure, the maximum systolic pressure difference across the tricuspid valve (Pmax), to examine the pulmonary vascular response to changes in blood flow during both air breathing and hypoxia. We used Doppler echocardiography in 33 resting healthy humans breathing air over 6–24 h to measure spontaneous diurnal variations in Pmax and cardiac output. Cardiac output varied by up to ~2.5 l/min; Pmax varied little with cardiac output [0.61±0.74 (SD) mmHg min l–1]. Eight of the volunteers were also exposed to eucapnic hypoxia (end-tidal
) for 8 h. In this group Pmax rose progressively from 21 mmHg to 37 mmHg over 8 h. By comparing diurnal variations in Pmax during air breathing with changes in Pmax during hypoxia in the same eight individuals, we concluded that only approximately 5% of the changes in Pmax during hypoxia could be attributed to concurrent changes in cardiac output. The low sensitivity of Pmax to changes in cardiac output makes it a useful index of hypoxic pulmonary vasoconstriction in healthy humans. 相似文献
28.
Paul Workman Richard A. S. White Kathleen Talbot 《Cancer chemotherapy and pharmacology》1986,16(1):1-8
Summary Although it has been the subject of considerable interest for 15 years, originally as a cytotoxic agent and more recently as a radiosensitizer, there is very little pharmacokinetic information on CB 1954 (2,4-dinitro-5-aziridinylbenzamide). We have developed a rapid high-performance liquid chromatography assay for the drug and its metabolites and applied it to detailed examination of the pharmacokinetics of CB 1954 in mice and dogs. With IV administration a dose of 50 mg/kg gave peak blood concentrations of 100 g/ml in mice, while 25 mg/kg gave peak palsma concentrations of 27 g/ml in dogs. Peak concentrations were 3 to 5-fold lower for the IP route in mice and the oral route in dogs, and the bioavailabilities were 85% and 40%, respectively. Elimination t1/2 values were 1.4–2 h in mice and 2.5–4 h in dogs and were independent of route of administration. Plasma protein binding was 57% but tissue penetration in mice was generally good. Tumour: plasma ratios were 50%–90%, while brain: plasma ratios were lower, at 37%–50%. The parent drug and several metabolites were identified and quantified in mouse urine, the total recovery being 24%–29%, of which 16%–25% was parent drug. The metabolites were also found in the circulation and in tissues. No changes in pharmacokinetics were seen with repeated dosing in mice or with administration of the protective agent phenyl AIC. Phenobarbitone pretreatment produced a small reduction in elimination t1/2, mainly by accelerating aziridine ring removal. Allopurinol increased the blood levels of the 5-amino nitroreduction product. These studies provide a pharmacokinetic basis for interpreting the antitumour activity and toxicity of CB 1954, as well as for the development of new mixed-function sensitizers. 相似文献
29.
30.
Plutonium-237 decays mainly by electron capture with a half-life of 45 d. Alpha particles are emitted in only 5 x 10(-3)% of its disintegrations. This nuclide can now be produced with relatively small amounts of alpha-emitting contaminants so that, in principle, 237Pu can be used for studies of Pu biokinetics in man. However, because of its high specific activity, there was some doubt that its metabolism would be the same as that of the alpha- and beta-emitting isotopes of Pu normally encountered in the nuclear industry. In this study, the biokinetics of nearly "pure," high specific activity 237Pu are compared with those of lower specific activity, "impure" 237Pu containing significant amounts of alpha-emitting Pu, following administration to rats by intravenous injection as the citrate. Both the distribution and excretion of the "pure" and "impure" 237Pu used in the two studies were similar and also in good agreement with the results of previously reported studies using 239Pu and 241Pu citrate, thus validating the use of 237Pu for studies of Pu metabolism in man. Data on the biokinetics of 237Pu nitrate are also included. 相似文献