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21.
Astrid LA. Kuijpers Rolph Pfundt Patrick LJM Zeeuwen Henri OF. Molhuizen Edwin CM. Mariman Peter CM. van de Kerkhof Joost Schalkwijk 《Clinical genetics》1998,54(1):96-101
Psoriasis is a multifactorial skin disease characterised by epidermal abnormalities and infiltration by lymphocytes and polymorphonuclear leukocytes (PMN). Skin-derived antileukoproteinase (SKALP), also known as elafin, is a potent inhibitor of human leukocyte elastase and proteinase 3, two PMN-derived proteinases implicated in tissue destruction and leukocyte migration. We have shown that, at least at the protein level, SKALP is significantly decreased in lesional skin of patients with pustular psoriasis compared with plaque-type psoriasis. This finding raised the possibility that SKALP could be one of the candidate genes for pustular forms of psoriasis. We therefore performed single strand conformation polymorphism (SSCP) analysis on the SKALP gene to screen for mutations/polymorphisms in the exons of 30 patients with plaque-type psoriasis, 15 patients with pustular psoriasis and 48 healthy controls. In exon 1 a polymorphism was detected at position + 43 relative to the translation start site, resulting in a substitution of threonine for alanine in the signal peptide. In the promoter region a dinucleotide repeat polymorphism was identified. Both polymorphisms were not associated with pustular psoriasis, or psoriasis in general. Our data indicate that the decrease in SKALP activity in pustular psoriasis is not caused by mutations in the coding region of the gene, and that there is no allelic association between pustular psoriasis and SKALP gene polymorphisms. 相似文献
22.
Association of DLG5 R30Q variant with inflammatory bowel disease 总被引:6,自引:0,他引:6
Daly MJ Pearce AV Farwell L Fisher SA Latiano A Prescott NJ Forbes A Mansfield J Sanderson J Langelier D Cohen A Bitton A Wild G Lewis CM Annese V Mathew CG Rioux JD 《European journal of human genetics : EJHG》2005,13(7):835-839
Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal system known as the inflammatory bowel diseases (IBD). Recently, Stoll and colleagues reported a novel finding of genetic variation in the DLG5 gene that is associated with IBD (CD and UC combined). We present here a study of the genetic variation described in that report in two well-powered, independent case-control cohorts and one family-based collection, and confirm the proposed association between IBD and the R30Q variant of DLG5 in two of the three studies. We are, however, unable to replicate the other proposed association to the common haplotype described in Stoll et al and suggest that this other finding could conceivably have been partially a statistical fluctuation and partially a result of LD with the replicated R30Q association. This study provides support for the hypothesis that DLG5 constitutes a true IBD risk factor of modest effect. 相似文献
23.
Five hundred allergy clinic patients were prick skin tested with papain, 1 mg/mL, in addition to usual local aeroallergens. Five of 475 subjects with seasonal allergic disease had positive skin tests to both papain and local pollens. None of the 25 individuals with negative skin test to pollens had skin reactivity to papain. The five subjects with positive skin tests to papain underwent double-blind placebo-papain challenges. All papain challenges were positive. Placebo challenges were negative. Papain-induced symptoms included palatal itching, watering itchy eyes, sneezing, rhinorrhea, abdominal cramps, diarrhea, and diaphoresis. Circulating papain-specific IgE was detected in all the papain-sensitive individuals, but not in control subjects. Confirmed papain sensitivity occurred in 1.05% of allergic subjects. In the papain-sensitive patients, cross-reacting antibodies with chymopapain were found. The small number of non-allergic subjects did not show any papain or chymopapain sensitivity in vitro. 相似文献
24.
Dal Zotto L; Quaderi NA; Elliott R; Lingerfelter PA; Carrel L; Valsecchi V; Montini E; Yen CH; Chapman V; Kalcheva I; Arrigo G; Zuffardi O; Thomas S; Willard HF; Ballabio A; Disteche CM; Rugarli EI 《Human molecular genetics》1998,7(3):489-499
We have recently reported isolation of the gene responsible for X- linked
Opitz G/BBB syndrome, a defect of midline development. MID1 is located on
the distal short arm of the human X chromosome (Xp22. 3) and encodes a
novel member of the B box family of zinc finger proteins. We have now
cloned the murine homolog of MID1 and performed preliminary expression
studies during development. Mid1 expression in undifferentiated cells in
the central nervous, gastrointestinal and urogenital systems suggests that
abnormal cell proliferation may underlie the defect in midline development
characteristic of Opitz syndrome. We have also found that Mid1 is located
within the mouse pseudoautosomal region (PAR) in Mus musculus , while it
seems to be X- specific in Mus spretus. Therefore, Mid1 is likely to be a
recent acquisition of the M. musculus PAR. Genetic and FISH analyses also
demonstrated a high frequency of unequal crossovers in the murine PAR,
creating spontaneous deletion/duplication events involving Mid1. These data
provide evidence for the first time that genetic instability of the PAR may
affect functionally important genes. In addition, we show that MID1 is the
first example of a gene subject to X-inactivation in man while escaping it
in mouse. These data contribute to a better understanding of the molecular
content and evolution of the rodent PAR.
相似文献
25.
Harry S. Spaulding Jr. M.D.COL MC Lyndon E. Mansfield M.D.LTC MC Mark R. Stein M.D. John C. Sellner M.D. Daniel E. Gremillion M.D. 《The Journal of allergy and clinical immunology》1982,69(6):516-521
A double-blind modification of the intraesophageal acid perfusion challenge (Bernstein procedure) was performed in asthmatic subjects with and without gastroesophageal reflux, nonasthmatic subjects with reflux, and normal subjects. Conventional spirometric functions and total respiratory resistance (Rrs) were measured prior to and after the infusion. There were no changes in pulmonary functions except in the asthmatic subjects who had had a positive add challenge. The greatest changes occurred in Rrs, which increased significantly with reflux symptoms (p < 0.01) and decreased toward baseline (p < 0.05) when these symptoms were relieved with antacids. The response was even greater in asthmatic subjects who associated reflux symptoms with attacks of asthma. These results support previous findings that acid reflux symptoms could cause a bronchoconstrictive response in certain asthmatic patients. 相似文献
26.
Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease 总被引:11,自引:4,他引:11
Cruts M; van Duijn CM; Backhovens H; Van den Broeck M; Wehnert A; Serneels S; Sherrington R; Hutton M; Hardy J; St George-Hyslop PH; Hofman A; Van Broeckhoven C 《Human molecular genetics》1998,7(1):43-51
Two closely related genes, the presenilins ( PS ), located at chromosomes
14q24.3 and 1q42.1, have been identified for autosomal dominant Alzheimer
disease (AD) with onset age below 65 years (presenile AD). We performed a
systematic mutation analysis of all coding and 5'-non-coding exons of PS -1
and PS -2 in a population-based epidemiological series of 101 unrelated
familial and sporadic presenile AD cases. The familial cases included 10
patients of autosomal dominant AD families sampled for linkage analysis
studies. In all patients mutations in the amyloid precursor protein gene (
APP ) had previously been excluded. Four different PS -1 missense mutations
were identified in six familial cases, two of which where autosomal
dominant cases. Three mutations resulted in onset ages above 55 years, with
one segregating in an autosomal dominant family with mean onset age 64
years (range 50-78 years). One PS -2 mutation was identified in a sporadic
case with onset age 62 years. Our mutation data provided estimates for PS
-1 and PS -2 mutation frequencies in presenile AD of 6 and 1% respectively.
When family history was accounted for mutation frequencies for PS -1 were
9% in familial cases and 18% in autosomal dominant cases. Further,
polymorphisms were detected in the promoter and the 5'-non-coding region of
PS -1 and in intronic and exonic sequences of PS -2 that will be useful in
genetic association studies.
相似文献
27.
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29.
L Ozzello CM De Rosa EW Blank K Cantell RL Ceriani DV Habif Sr 《Breast cancer research and treatment》1993,25(3):265-276
Summary An immunoconjugate composed of natural interferon (nIFN) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN on the injected tumors. Further enhancement was obtained when nIFN or nIFN together with Mc5 (at a dose 10 times larger than that present in nIFN/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of125I-nIFN/Mc5 by the tumors was greater and its elimination slower than for125I-nIFN alone or conjugated to irrelevant mouse IgG1. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy. 相似文献
30.
To find out the efficacy of sucralfate in preventing gastrointestinal side effects of non-steroidal anti-inflammatory drugs (NSAIDs) a prospective, randomised single blind study was conducted from 1989 to 1992. Patients with osteoarthritis, rheumatoid arthritis and other long standing painful conditions, who were expected to receive NSAIDs for over three months, were recruited into the study. All medicines were discontinued for a period of 10–15 days prior to initial endoscopic assessment. NSAID therapy was started and the patients were randomised to receive either placebo (group A) or sucralfate (group B) in addition. Patient were reassessed clinically every week and an endoscopic examination was repeated after 6–8 weeks of follow-up. A total of 176 patients were studied in group A (n=91) and group B (n=85). At the end of 8 weeks gastrointestinal symptoms were present in 30.6% and 26.4% patients of group A and B respectively. Endoscopic assessment showed superficial lesions in 36.5% and 18.7% while endoscopic ulcer in 2.4% and 1.1% patients of groups A and B respectively. Thus in patients receiving chronic NSAID therapy, simultaneous administration of sucralfate reduces the incidence of superficial gastric lesions but has no significant effect on symptoms or ulcer formation.KEY WORDS: Gastropathy, Sucralfate, Nonsteroidal anti-inflammatory drugs 相似文献