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51.
Autologous immune complex glomerulopathy (AICG) is induced by immunizing rats with a crude brushborder fraction of rat kidney tubules (Fx1A) or with the purified GP 330 antigen. In these animals, anti-brushborder antibodies develop, leading to subepithelial immune complexes along the glomerular capillary wall. In rats with AICG, thymocytes sensitized against Fx1A as well as thymocytes recognizing anti-Fx1A are present. These latter cells might play a role in the specific tolerance against the pathogenetic antigen GP 330. To substantiate this notion, immunofluorescence studies were performed in which the number of anti-GP 330 binding cells was quantified in thymus cell suspensions of rats with AICG, in control rats and in naive rats with different genetic background. It is shown that increased numbers of anti-GP 330-binding thymocytes in rats with AICG are associated with a decline in the serum anti-brushborder titer. Furthermore, it appears that the number of anti-GP 330-binding thymocytes in naive rats of the non-responder Brown Norway strain is significantly higher as compared to the PVG/c and Lewis strains, which are susceptible for AICG. The correlation between the numbers of anti-GP 330-binding thymocytes and the susceptibility for AICG suggests a role for these cells in maintaining the tolerance against the Fx1A (GP 330) antigen. 相似文献
52.
Organization and expression of genes involved in the production of the K88ab antigen 总被引:27,自引:7,他引:27
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Escherichia coli K-12 minicells were used to study the expression of the genes located on plasmid pFM205, which contains the genetic determinant of the K88ab antigen. Plasmid pFM205 is composed of a 4,3-megadalton large deoxyribonucleic acid fragment derived from the wild-type K88ab plasmid pRI8801 (51 megadaltons) and the cloning vehicle pBR322. The K88ab deoxyribonucleic acid of pFM205 appeared to express six polypeptides with apparent molecular masses of 81, 30, 29, 27, 26, and 17 kilodaltons, respectively. These polypeptides account for approximately 85% of the coding capacity of the cloned deoxyribonucleic acid. The 26-kilodalton polypeptide was found to react with specific anti-K88ab antibodies and therefore represents the K88ab subunit. The K88ab subunit and at least two other polypeptides (81 and 17 kilodaltons) were translated into precursors which were about 2 kilodaltons larger than the mature proteins. Plasmid pFM205 was used to construct deletion mutants. By analyzing these mutants in minicells the genes of the six polypeptides could be located on the physical map of pFM205. It appeared that deletion of the gene of the 81-kilodalton polypeptide resulted in an altered conformation of the K88ab antigen. 相似文献
53.
Antibodies to HTLV-I in populations of the southwestern Pacific 总被引:6,自引:0,他引:6
D M Asher J Goudsmit K L Pomeroy R M Garruto M Bakker S G Ono N Elliot K Harris H Askins Z Eldadah 《Journal of medical virology》1988,26(4):339-351
Sera collected from 1,102 individuals in 14 populations of the southwestern Pacific between 1956 and 1979 were tested by ELISA for antibodies to human T-cell leukemia virus type I (HTLV-I). Selected sera were also tested by particle agglutination and immunoblotting. Six of the populations had prevalences of antibodies greater than 4%, two populations had prevalences greater than 15%. Six populations had antibody prevalences of 2% or less. Three populations from the coast and northern islands of New Guinea had high prevalences of antibodies, while three New Guinea highland groups had virtually none. One population from the Solomon Islands had a high prevalence, while two others had very low prevalences. Two populations from small remote islands in Vanuatu both had high prevalences. Pacific sera did not neutralize a standard strain of virus readily neutralized by Japanese, European, and American sera. We conclude that infections with HTLV-I, some acquired more than 20 years ago, are widespread throughout the southwestern Pacific, even in several very isolated populations, although others have been spared. Some strains of HTLV-I in populations of the Pacific may have substantially different envelope proteins from prototype strains of America, Europe, and Japan. 相似文献
54.
Diagnostic, predictive, and prenatal testing for facioscapulohumeral muscular dystrophy: diagnostic approach for sporadic and familial cases. 总被引:3,自引:1,他引:3
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E Bakker M J Van der Wielen E Voorhoeve P F Ippel G W Padberg R R Frants C Wijmenga 《Journal of medical genetics》1996,33(1):29-35
Facioscapulohumeral muscular dystrophy (FSHD) is one of the common inherited neuromuscular disorders. The major gene involved, FSHD1, has been localised to chromosome 4q35. This 4q35 locus, detected by pE13-11 (D4F104S1), shows a mutation frequency of about 10% of the incidence. New mutants are characterised by de novo deletions of tens to hundreds of kilobases of DNA. Although these deletion fragments are very useful as a molecular genetic tool, their use in diagnostic DNA testing is hampered by multiple factors, particularly in familial cases. In this report we describe a protocol that can be used for DNA testing in well defined familial cases or proven de novo cases, and in the differential diagnosis of muscular dystrophy patients clinically suspected of having FSHD. In addition, we describe a prenatal diagnosis performed for FSHD1. 相似文献
55.
Wang Q Verhoef S Tempelaars AM Bakker PL Vrtel R Hesseling-Janssen AL Nellist M Oranje AP Stroink H Lindhout D Halley DJ van den Ouweland AM 《Human mutation》1998,11(4):331-332
Important symptoms of tuberous sclerosis complex (TSC), an autosomal dominant disorder, are hamartomata in several organs, mental retardation and epilepsy. Either one of two loci can be involved (TSC1 and TSC2), of which the TSC2 gene has been cloned. To date, only 35 mutations in the TSC2 gene have been described ranging from large deletions to point mutations. Southern blot analysis using cDNA clones of the TSC2 gene was performed on a cohort of 160 unrelated TSC patients and revealed a 10 kb insertion. The insertion was also present in DNA of the affected father. Both patients showed renal angiomyolipoma, hypomelanotic macules and epilepsy. SSCP analysis of exons 1,2,3,9,12,14,30a and 36 identified two mutations in exon 30a: 3671del8 and S1221X. Symptoms of the sporadic patient with the 3671del8 mutation are cortical tubers, subependymal nodules, facial angiofibroma, ungual fibroma, renal angiomyolipoma, hypomelanotic macules, epilepsy and mental retardation. Clinical symptoms of the patient with the S1221X mutation are facial angiofibroma, ungual fibroma, hypomelanotic macules, epilepsy and mental retardation. His parents were negative for the S1221X mutation, although a germline mosaicism can not be excluded. Besides the previously described polymorphism 1596C->T, two rare variants were observed, a substitution of C->T at position 1294 and at position 1299 C->A. 相似文献
56.
Teun P De Boer Bart Kok Kirsten I E Neuteboom Nicole Spieker Jochum De Graaf Olivier H J Destrée Martin B Rook Toon A B Van Veen Habo J Jongsma Marc A Vos Jacques M T De Bakker Marcel A G Van Der Heyden 《Developmental dynamics》2005,233(3):864-871
Connexin-containing gap junctions play an essential role in vertebrate development. More than 20 connexin isoforms have been identified in mammals. However, the number identified in Xenopus trails with only six isoforms described. Here, identification of a new connexin isoform from Xenopus laevis is described. Connexin40.4 was found by screening expressed sequence tag databases and carrying out polymerase chain reaction on genomic DNA. This new connexin has limited amino acid identity with mammalian (<50%) connexins, but conservation is higher (approximately 62%) with fish. During Xenopus laevis development, connexin40.4 was first expressed after the mid-blastula transition. There was prominent expression in the presomitic paraxial mesoderm and later in the developing somites. In adult frogs, expression was detected in kidney and stomach as well as in brain, heart, and skeletal muscle. Ectopic expression of connexin40.4 in HEK293 cells, resulted in formation of gap junction like structures at the cell interfaces. Similar ectopic expression in neural N2A cells resulted in functional electrical coupling, displaying mild, asymmetric voltage dependence. We thus cloned a novel connexin from Xenopus laevis, strongly expressed in developing somites, with no apparent orthologue in mammals. 相似文献
57.
Hofstra RM Mulder IM Vossen R de Koning-Gans PA Kraak M Ginjaar IB van der Hout AH Bakker E Buys CH van Ommen GJ van Essen AJ den Dunnen JT 《Human mutation》2004,23(1):57-66
Duchenne and Becker muscular dystrophy (DMD and BMD) are caused by mutations in the dystrophin gene. Large rearrangements in the gene are found in about two-thirds of DMD patients, with approximately 60% carrying deletions and 5-10% carrying duplications. Most of the remaining 30-35% of patients are expected to have small nucleotide substitutions, insertions, or deletions. To detect these subtle changes within the coding and splice site determining sequences of the dystrophin gene, we established a semiautomated denaturing gradient gel electrophoresis (DGGE) mutation scanning system. The DGGE scan covers the dystrophin gene with 95 amplicons, PCRed either individually or in a multiplex setup. PCR and pooling were performed semiautomatically, using a pipetting robot and 384-well plates, enabling concurrent amplification of DNA of four patients in one run. Amplification of individual fragments was performed using one PCR program. The products were pooled just before gel loading; DGGE requires only a single gel condition. Validation was performed using DNA samples harboring 39 known DMD variants, all of which could be readily detected. DGGE mutation scanning was applied to analyze 135 DMD/BMD patients and potential DMD carriers without large deletions or duplications. In DNA from 25 out of 44 DMD patients (57%) and from 5 out of 39 BMD patients (13%), we identified clear pathogenic changes. All mutations were different, with the exception of one DMD mutation, which occurred twice. In DNA from 10 out of 44 potential DMD carriers, including four obligate carriers, we detected causative changes, including one pathogenic change in every obligate carrier. In addition to these pathogenic changes, we detected 15 unique unclassified variants, i.e., changes for which a pathogenic nature is uncertain. 相似文献
58.
Expression of Ep-CAM in cervical squamous epithelia correlates with an increased proliferation and the disappearance of markers for terminal differentiation. 总被引:7,自引:3,他引:7
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S. V. Litvinov W. van Driel C. M. van Rhijn H. A. Bakker H. van Krieken G. J. Fleuren S. O. Warnaar 《The American journal of pathology》1996,148(3):865-875
Ep-CAM, an epithelial adhesion molecule, is absent in normal squamous epithelia but can be detected in some squamous carcinomas. Using a panel of monoclonal antibodies to keratinocyte differentiation and proliferation markers, we investigated the association of EP-CAM expression with differentiation-related and/or neoplastic changes in cervical epithelium. Normal endocervical glandular epithelium (Both columnar and reserve cells) appeared strongly positive for EP-CAM, whereas ectocervical squamous epithelial cells did not express this molecule. Expression of Ep-CAM (in basal cells) was sometimes observed in morphologically normal ectocervical tissue but only in areas bordering cervical intraepithelial neoplasia (CIN) lesions. At the early stages of neoplasia the expression of Ep-CAM was regularly present in squamous epithelium, in general consistent with the areas of atypical, undifferentiated cells. Thus, in CIN grades I and II, the basal/suprabasal layers of the epithelia were positive, whereas in CIN grade III lesions, up to 100% of the cells over the whole thickness of the epithelium sometimes excluding the very upper layers, expressed Ep-CAM. A clear increase, not only in number of positive cells but also in levels of Ep-CAM expression (intensity) was observed during progression from CIN I to CIN III. Expression of Ep-CAM in ectocervical lesions did not coincide with a reappearance of the simple epithelium cytokeratins (CK8 and CK18). On the other hand, expression of Ep-CAM in atypical cells of CIN lesions correlated with the disappearance of CK13, which normally marks cells undergoing squamous differentiation. As was shown with Ki-67, a marker for proliferating cell populations, the areas of Ep-CAM expression were also the areas of enhanced proliferation. Cells expressing Ep-CAM did not express involucrin, a marker for cells committed to terminal differentiation. In the majority of both squamous and adenocarcinomas of the cervix a strong expression of Ep-CAM was observed, although some decrease in the expression (both the intensity and the number of positive cells), as compared with CIN III lesions, was observed in the areas of squamous differentiation. This study demonstrates that the expression of Ep-CAM in cervical squamous epithelium is associated with abnormal proliferation of cell populations that are not committed to terminal differentiation. 相似文献
59.
Roewer L; Kayser M; Dieltjes P; Nagy M; Bakker E; Krawczak M; de Knijff P 《Human molecular genetics》1996,5(7):1029-1033
The analysis of seven Y-chromosome-specific microsatellite loci revealed a
high level of polymorphism in two closely related human populations (Dutch,
n = 89, and German, n = 70). Four of these loci were found to generate at
least 77 different haplotypes, only 15 of which were shared by the two
populations. These results demonstrate that highly informative PCR-based
DNA typing of the Y chromosome is now feasible. Assuming a stepwise
mutation model, a network comprising all minimum spanning evolutionary
trees connecting the haplotypes was constructed. Analysis of molecular
variance based upon this network indicated that the within-population
heterogeneity with respect to haplotype descent was significantly smaller
than the between-population heterogeneity, suggesting that males were more
closely related to males from their own population as opposed to males from
the other population. These findings suggest that Y-chromosomal
microsatellites might be very useful not only for forensic purposes but
also in association studies of multifactorial traits, allowing the
characterization of the level of genetic distinctiveness of supposedly
inbred or isolated populations and discrimination even between closely
related populations.
相似文献
60.
B. Ilmer A. E. M. Reijs J. H. C. Reiber W. Bakker P. Fioretti 《The international journal of cardiovascular imaging》1990,6(2):135-141
Uptake of thallium (Tl)-201 in the lungs has been proposed as a measure of left ventricular dysfunction. In this study we were interested in pursuing two goals: 1) to assess possible relationships between the post-exercise Tl-201 lung-heart (LH-) ratio determined from the anterior view during SPECT-acquisition, myocardial ischemia and the extent of coronary artery disease; and 2) to explore the effects of coronary revascularisation procedures on the LH-ratio. The study group consisted of 145 patients with early and late postexercise Tl-201 tomograms, including 32 PTCA-patients with pre- and post-PTCA studies and 20 patients who underwent coronary artery bypass surgery (CABG) with corresponding pre- and post-CABG studies. Ischemia was defined as evoked angina during the exercise test in combination with ≥1 mm horizontal or downsloping ST-depression on the ECG. The severity of coronary obstructions was assessed from coronary angiograms with a PC-based digital caliper technique; a stenosis was defined to be significant when its severity exceeded 50% diameter stenosis. The LH-ratio was defined by the ratio of the mean pulmonary counts and the mean myocardial counts assessed from corresponding regions of interest (ROI's) positioned over the left lung and the heart, respectively in the anterior view of a tomographic data acquisition procedure. Our results made clear that the LH-ratio was not significantly different between patients with and without ischemia during exercise, and between patients with single vs. multiple vessel disease. However, the interventions had a significant effect of the LH-ratio:
LH-ratio mean ± s.d. 相似文献
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