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21.
Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease. 总被引:1,自引:0,他引:1
Collins CE Benson MJ Burnham WR Rampton DS 《Alimentary pharmacology & therapeutics》1996,10(3):315-320
BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease. 相似文献
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The feasibility of a state policy to permit home care agencies to hire kin as caregivers was explored by examining existing data on a state program that allowed relatives to be hired. Of 444 clients, 22% had kin as paid caregivers. Co-residence and kinship were associated with higher disability levels and a higher level of eligibility for services as determined by a functional assessment tool used by the state to determine care plans. The limited number of clients with paid caregivers who were kin suggests that there may be a natural limit to the demand for such an option. 相似文献
24.
With regard to cadmium toxicity, Drosophila strains v;bw and Austin represent extremes in resistance and sensitivity, respectively. Both strains produced metallothionein (MT) in response to Cd ions in their diet. Austin produced more metallothionein than v;bw at Cd ion levels below 0.2 mM, when both strains were allowed lifetime development on Cd2+-containing media. When the rate of MT appearance was measured for 4 days in young adults the results showed no clear trend with time within a strain or between strains. The plot of LC50 vs. MT levels for identical developmental conditions revealed that for v;bw small increases in MT corresponded to large increases in resistance whereas for the sensitive Austin even large increases in MT had comparatively little effect on increasing LC50. Results given here suggest that differences in total MT content do not explain the genetically demonstrable difference in Cd2+-resistance between v;bw and Austin. However, since two MT genes are identified in Drosophila, differences in resistance could be reflective of greater relative amounts of one "more important" MT in the resistant fly. 相似文献
25.
Relative carriage rates of nuclear dehydrogenating clostridia in two populations of different colorectal cancer risk
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Carriage of nuclear dehydrogenating clostridia has been associated with colon cancer and implicated in its aetiology. This study has compared the carriage of these organisms in a British population at high risk for the development of colon cancer with a low risk Nigerian population. Clostridia were found in all of the stools from both populations. Nuclear dehydrogenating clostridia were only found in the stools of the British subjects (32%). These results support the suggestion that the carriage rate of nuclear dehydrogenating clostridia in a population is related to the risk of colon cancer. 相似文献
26.
Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability 总被引:1,自引:15,他引:1
La Spada AR; Peterson KR; Meadows SA; McClain ME; Jeng G; Chmelar RS; Haugen HA; Chen K; Singer MJ; Moore D; Trask BJ; Fischbeck KH; Clegg CH; McKnight GS 《Human molecular genetics》1998,7(6):959-967
X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG
repeat expansion in the first exon of the androgen receptor (AR) gene.
Disease-associated alleles (37-66 CAGs) change in length when transmitted
from parents to offspring, with a significantly greater tendency to shift
size when inherited paternally. As transgenic mice carrying human AR cDNAs
with 45 and 66 CAG repeats do not display repeat instability, we attempted
to model trinucleotide repeat instability by generating transgenic mice
with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions
in their genomic context. Studies of independent lines of AR YAC transgenic
mice with CAG 45 alleles reveal intergenerational instability at an overall
rate of approximately 10%. We also find that the 45 CAG repeat tracts are
significantly more unstable with maternal transmission and as the
transmitting mother ages. Of all the CAG/CTG repeat transgenic mice
produced to date the AR YAC CAG 45 mice are unstable with the smallest
trinucleotide repeat mutations, suggesting that the length threshold for
repeat instability in the mouse may be lowered by including the appropriate
flanking human DNA sequences. By sequence-tagged site content analysis and
long range mapping we determined that one unstable transgenic line has
integrated an approximately 70 kb segment of the AR locus due to
fragmentation of the AR YAC. Identification of the cis - acting elements
that permit CAG tract instability and the trans -acting factors that
modulate repeat instability in the AR YAC CAG 45 mice may provide insights
into the molecular basis of trinucleotide repeat instability in humans.
相似文献
27.
Paul Kruszka Tommy Hu Sungkook Hong Rebecca Signer Benjamin Cogné Betrand Isidor Sarah E. Mazzola Jacques C. Giltay Koen L. I. van Gassen Eleina M. England Lynn Pais Charlotte W. Ockeloen Pedro A. Sanchez‐Lara Esther Kinning Darius J. Adams Kayla Treat Wilfredo Torres‐Martinez Maria F. Bedeschi Maria Iascone Stephanie Blaney Oliver Bell Tiong Y. Tan Marie‐Ange Delrue Julie Jurgens Brenda J. Barry Elizabeth C. Engle Sarah K. Savage Nicole Fleischer Julian A. Martinez‐Agosto Kym Boycott Elaine H. Zackai Maximilian Muenke 《American journal of medical genetics. Part A》2019,179(10):2075-2082
Zinc finger protein 462 (ZNF462) is a relatively newly discovered vertebrate specific protein with known critical roles in embryonic development in animal models. Two case reports and a case series study have described the phenotype of 10 individuals with ZNF462 loss of function variants. Herein, we present 14 new individuals with loss of function variants to the previous studies to delineate the syndrome of loss of function in ZNF462. Collectively, these 24 individuals present with recurring phenotypes that define a multiple congenital anomaly syndrome. Most have some form of developmental delay (79%) and a minority has autism spectrum disorder (33%). Characteristic facial features include ptosis (83%), down slanting palpebral fissures (58%), exaggerated Cupid's bow/wide philtrum (54%), and arched eyebrows (50%). Metopic ridging or craniosynostosis was found in a third of study participants and feeding problems in half. Other phenotype characteristics include dysgenesis of the corpus callosum in 25% of individuals, hypotonia in half, and structural heart defects in 21%. Using facial analysis technology, a computer algorithm applying deep learning was able to accurately differentiate individuals with ZNF462 loss of function variants from individuals with Noonan syndrome and healthy controls. In summary, we describe a multiple congenital anomaly syndrome associated with haploinsufficiency of ZNF462 that has distinct clinical characteristics and facial features. 相似文献
28.
J. M. England M. J. Panella G. C. Kopen T. W. Wisner M. S. Halpern 《Virchows Archiv : an international journal of pathology》1994,424(1):83-88
The observation that v-src-induced tumors contain tumor cells of differing morphology, notably fibroblastoid or polygonal, raised the question as to whether the tumor cells are also heterogeneous with respect to expression of markers of cellular differentiation. Of the markers tested here, consistent reactivity for tumor tissue was noted only for antibody probes reactive to muscle actin (HHF35, sm-1) or to procollagen type I (SP1. D8); for any given tumor, whether induced by v-src DNA or by Rous sarcoma virus, each of these markers was found only in a subpopulation of tumor cells. The observation of marker heterogeneity in the one v-src DNA-induced tumor examined here that typed as monoclonal suggests that v-src-induced transformation is consonant with a degree of plasticity in the phenotypes of the clonal progeny of a single transformant. 相似文献
29.
30.
Long Jin Jiangyue Song William F. Chandler Barry G. England James B. Smart Ariel Barkan Ricardo V. Lloyd 《Endocrine pathology》1990,1(1):25-36
The effects of the hypothalamic hormones, thyrotropin-releasing hormone (TRH), and somatostatin (SRIH), and of phorbol 12-myristate
13-acetate (PMA) on PRL and GH secretion and messenger RNA (mRNA) levels were analyzed in 10 GH and/or PRL producing adenomas
after culturing the tumor cells in the presence of these secretagogues for 7 days. The expression of chromogranin A and B
mRNAs was also examined. All four of the clinically diagnosed GH adenomas expressed or secreted both GH and PRL while four
of six clinically diagnosed prolactinomas produced or secreted both PRL and GH. Prolactinomas had less than 10% of tumor cells
expressing chromogranin A mRNA while more than 40% of the adenoma cells expressed chromogranin B mRNA. TRH stimulated PRL
secretion and increased PRL mRNA levels while SRIH decreased GH secretion and mRNA expression in some cases. Unexpectedly,
PMA stimulated PRL mRNA levels four- to sevenfold above control levels in two adenomas and generally stimulated chromogranin
A and B mRNA expression but not GH mRNA, as determined by Northern hybridization and in situ hybridization analyses.
These results indicate that cultured prolactinoma cells express significantly more chromogranin B mRNA than chromogranin A
mRNA, and that PMA increases PRL mRNA expression in some prolactinomas, although the effect of PMA on various adenomas reflects
the heterogeneity of these tumors with respect to protein kinase C stimulation. 相似文献