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11.
Arbour NC; Zlotogora J; Knowlton RG; Merin S; Rosenmann A; Kanis AB; Rokhlina T; Stone EM; Sheffield VC 《Human molecular genetics》1997,6(5):689-694
Achromatopsia is an autosomal recessive disease of the retina,
characterized clinically by an inability to distinguish colors, impaired
visual acuity, nystagmus and photophobia. A genome-wide search for linkage
was performed using an inbred Jewish kindred from Iran. To facilitate the
genome-wide search, we utilized a DNA pooling strategy which takes
advantage of the likelihood that the disease in this inbred kindred is
inherited by all affected individuals from a common founder. Equal molar
amounts of DNA from all affected individuals were pooled and used as the
PCR template for short tandem repeat polymorphic markers (STRPs). Pooled
DNA from unaffected members of the kindred was used as a control. A
reduction in the number of alleles in the affected versus control pool was
observed at several loci. Upon genotyping of individual family members,
significant linkage was established between the disease phenotype and
markers localized on chromosome 2. The highest LOD score observed was 5.4
(theta = 0). When four additional small unrelated families were genotyped,
the combined peak LOD score was 8.2. Analysis of recombinant chromosomes
revealed that the disease gene lies within a 30 cM interval which spans the
centromere. Additional fine-mapping studies identified a region of
homozygosity in all affected individuals, narrowing the region to 14 cM. A
candidate gene for achromatopsia was excluded from this disease interval by
radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an
essential first step in the identification of the disease-causing gene.
相似文献
12.
13.
Assessment of the mutagenicity of dichloroacetic acid in lacI transgenic B6C3F1 mouse liver 总被引:2,自引:0,他引:2
Dichloroacetic acid (DCA) is a chlorination byproduct found in finished
drinking water. When administered in drinking water this chemical has been
shown to produce hepatocellular adenomas and carcinomas in B6C3F1 mice over
the animal's lifetime. In this study, we investigated whether mutant
frequencies were increased in mouse liver using treatment protocols that
yielded significant tumor induction. DCA was administered continuously at
either 1.0 or 3.5 g/l in drinking water to male transgenic B6C3F1 mice
harboring the bacterial lacI gene. Groups of five or six animals were
killed at 4, 10 or 60 weeks and livers removed. At both 4 and 10 weeks of
treatment, there was no significant difference in mutant frequency between
the treated and control animals at either dose level. At 60 weeks, mice
treated with 1.0 g/l DCA showed a 1.3-fold increase in mutant frequency
over concurrent controls (P = 0.05). Mice treated with 3.5 g/l DCA for 60
weeks had a 2.3-fold increase in mutant frequency over the concurrent
controls (P = 0.002). The mutation spectrum recovered from mice treated
with 3.5 g/l DCA for 60 weeks contained G:C-->A:T transitions (32.79%)
and G:C-->T:A transversions (21.31%). In contrast, G:C-->A:T
transitions comprised 53.19% of the recovered mutants among control
animals. Although only 19.15% of mutations among the controls were at T:A
sites, 32.79% of the mutations from DCA-treated animals were at T:A sites.
This is consistent with the previous observation that the proportion of
mutations at T:A sites in codon 61 of the H-ras gene was increased in
DCA-induced liver tumors in B6C3F1 mice. The present study demonstrates
DCA-associated mutagenicity in the mouse liver under conditions in which
DCA produces hepatic tumors.
相似文献
14.
Female sterilisation is an important component of National Family Welfare Programme. The target group is best motivated during the puerperium for such a procedure. However laparoscopic sterilisation which has got some distinct advantages, is not technically feasible at this time. The authors have used a technique where the advantages of cosmetic appearance, reduced post operative morbidity and reversibility can be conferred on the puerperal women.After trying out the method individually in some cases, a formal case control study design has been made and an evaluation study has been performed in 122 cases. The technique has been found to be cosmetically more acceptable, both at clientele and peer evaluation levels (p<0.001). Though all the four parameters of post operative morbidity have shown better results for the technique evaluated as against the conventional technique, statistical significance has been achieved in two of the parameters (p<0.05).KEY WORDS: Cosmetics, Female sterilisation, Post operative morbidity 相似文献
15.
Maria B Sukkar Md Ashik Ullah Wan Jun Gan Peter AB Wark Kian Fan Chung J Margaret Hughes Carol L Armour Simon Phipps 《British journal of pharmacology》2012,167(6):1161-1176
Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous inflammatory disorders of the respiratory tract characterized by airflow obstruction. It is now clear that the environmental factors that drive airway pathology in asthma and COPD, including allergens, viruses, ozone and cigarette smoke, activate innate immune receptors known as pattern-recognition receptors, either directly or indirectly by causing the release of endogenous ligands. Thus, there is now intense research activity focused around understanding the mechanisms by which pattern-recognition receptors sustain the airway inflammatory response, and how these mechanisms might be targeted therapeutically. One pattern-recognition receptor that has recently come to attention in chronic airways disease is the receptor for advanced glycation end products (RAGE). RAGE is a member of the immunoglobulin superfamily of cell surface receptors that recognizes pathogen- and host-derived endogenous ligands to initiate the immune response to tissue injury, infection and inflammation. Although the role of RAGE in lung physiology and pathophysiology is not well understood, recent genome-wide association studies have linked RAGE gene polymorphisms with airflow obstruction. In addition, accumulating data from animal and clinical investigations reveal increased expression of RAGE and its ligands, together with reduced expression of soluble RAGE, an endogenous inhibitor of RAGE signalling, in chronic airways disease. In this review, we discuss recent studies of the ligand–RAGE axis in asthma and COPD, highlight important areas for future research and discuss how this axis might potentially be harnessed for therapeutic benefit in these conditions. 相似文献
16.
Hand‐foot‐skin reaction related to use of the multikinase inhibitor sorafenib and hard orthotics
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Ayan Kusari MA Jenna Borok MAS Allison M. Han AB Alix Jessika Valderrama MD Sheila Fallon Friedlander MD 《Pediatric dermatology》2018,35(4):e206-e209
Hand‐foot‐skin reaction is a distinct clinical condition arising in association with the use of multikinase inhibitors, including sorafenib. Because multikinase inhibitors are increasingly being used in children with cancer, recognition of this previously unfamiliar condition is of importance to pediatric dermatologists. We describe the diagnosis and successful treatment of a case of hand‐foot‐skin reaction in a child taking sorafenib for an unresectable desmoid tumor. 相似文献
17.
Cytogenetic and molecular analysis in Philadelphia negative CML 总被引:2,自引:0,他引:2
van der Plas DC; Hermans AB; Soekarman D; Smit EM; de Klein A; Smadja N; Alimena G; Goudsmit R; Grosveld G; Hagemeijer A 《Blood》1989,73(4):1038-1044
18.
A new variant of type II von Willebrand disease with aberrant multimeric structure of plasma but not platelet von Willebrand factor (type IIF) 总被引:2,自引:0,他引:2
A patient with a lifelong bleeding disorder was diagnosed as having Type II von Willebrand disease. The larger multimers of von Willebrand factor were absent from her plasma but present in platelets. A high- resolution electrophoretic technique was used to study the complex structure of individual von Willebrand factor multimers. In normal plasma, each multimer could be resolved into five bands: a more intense central one and four less intense, two moving faster and two slower than the central band. In normal platelets, each multimer could also be resolved into five bands. The central one had a mobility similar to that in plasma, whereas the four satellite bands had a mobility that differed from that of the corresponding plasma bands. In the patient, platelet von Willebrand factor antigen content and ristocetin cofactor activity were normal, and von Willebrand factor showed the same structure of individual multimers as seen in normal platelets. On the other hand, plasma von Willebrand factor antigen and ristocetin cofactor activity were decreased, and the structure of individual von Willebrand factor multimers was different from that of normal plasma and similar to that seen in normal and patient's platelets. After infusion of 1-deamino-8-D-arginine vasopressin, the largest von Willebrand factor multimers, as well as new satellite bands with a mobility similar to those in normal plasma, appeared in the patient plasma, and the levels of von Willebrand factor antigen and ristocetin cofactor activity became normal. Yet no relevant change in the prolonged bleeding time was observed. This new variant of von Willebrand disease, therefore, is characterized by the presence of a dysfunctional von Willebrand factor molecule that exhibits unique structural abnormalities in plasma but appears to be normal in platelets. The designation of Type IIF is proposed for this type of von Willebrand disease in accordance with the terminology that has been previously used. 相似文献
19.
Dr. Erica A. Brotschi MD Carol L. Hilbinger BA Elizabeth A. Kahl AB William A. Vaules AB Nicholas A. Midis AB J. Krzysztof Blusztajn PhD Stephen H. Zeisel MD PhD 《Digestive diseases and sciences》1995,40(9):1982-1989
Acetylcholine may be released from gallbladder intrinsic nerves in response to cholecystokinin stimulation. This study characterized metabolites of [14C]choline produced in the gallbladder and released during incubation, with or without cholecystokinin-octapeptide. Radiolabeled [14C]choline was applied to the mucosal or muscle surface of intact guinea pig gallbladders in an organ bath. After radiolabeling, gallbladders were incubated with or without the contractile agonist cholecystokinin-octapeptide. Metabolites of [14C]choline were identified in gallbladder tissue and incubation buffers using HPLC and thin-layer chromatography. The major metabolites of [14C]choline were betaine and phosphocholine. [14C]Phosphocholine was incorporated slowly into [14C]phosphatidylcholine. [14C]Choline was released into buffers during incubation. [14C]Acetylcholine constituted less than 1% of radiolabel in the gallbladder. There was no identifiable [14C]acetylcholine released in buffers. Cholecystokinin-octapeptide did not affect choline metabolism. These studies showed that choline in the gallbladder is metabolized along pathways similar to those in the liver. Gallbladders released mostly choline, rather than acetylcholine, even during hormonally induced contraction.This project was supported by the Research and Development Office of the Department of Veterans Affairs. 相似文献
20.
Association of granulocyte-macrophage colony-stimulating factor with the crystalloid granules of human eosinophils 总被引:3,自引:1,他引:3
Levi-Schaffer F; Lacy P; Severs NJ; Newman TM; North J; Gomperts B; Kay AB; Moqbel R 《Blood》1995,85(9):2579-2586
We have previously shown that normal-density human peripheral blood eosinophils transcribe and translate mRNA for granulocyte-macrophage colony-stimulating factor (GM-CSF) and that the intracellular distribution was granular as assessed by light microscopy immunocytochemistry. The present study was conducted to confirm this apparent association between GM-CSF and the crystalloid granule using a subcellular fractionation method for human eosinophils and immunogold electron microscopy (EM). Highly purified (> 99%, by negative selection using anti-CD16 immunomagnetic microbeads) human peripheral blood eosinophils were obtained from four asthmatic subjects (not taking systemic medication), homogenized and density fractionated (5 x 10(7) cells/subject) on linear Nycodenz gradients. Twenty-four fractions were collected from each cell preparation and analyzed for marker enzyme activities as well as total protein. Dot blot analysis with specific monoclonal antibodies (MoAbs) was used to detect the eosinophil granule proteins major basic protein (MBP) and eosinophil cationic protein (ECP). An anti-CD9 MoAb was used as an eosinophil plasma membrane marker. Lactate dehydrogenase (LDH) was used as a cytosolic marker. Immunoreactivity for GM-CSF was detected by a specific enzyme-linked immunosorbent assay using a polyclonal antihuman GM-CSF antibody and confirmed by dot blot. GM-CSF coeluted with the cellular fractions containing granule markers (MBP, ECP, eosinophil peroxidase, hexosaminidase, and arylsulphatase), but not those containing cytoplasm (LDH+) or membrane (CD9+) markers. EM examination of pooled fractions associated with the peak of GM-CSF immunoreactivity confirmed that they contained crystalloid and small granules, but not plasma membrane. In addition, quantification, using immunogold labeling with an anti/GM-CSF MoAb, indicated preferential localization of gold particles over the eosinophil granule cores of intact cells. Thus, our results indicate that GM-CSF resides as a granule-associated, stored mediator in unstimulated human eosinophils. 相似文献