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Chairat Shayakul Petr Jarolim Marie Zachlederova Daniel Prabakaran Dionisio Cortez-Campeao Dana Kalabova Alan K Stuart-Tilley Hiroshi Ideguchi Christlieb Haller Seth L Alper 《Nephrology, dialysis, transplantation》2004,19(2):371-379
BACKGROUND: Mutations in the human SLC4A1 (AE1/band 3) gene are associated with hereditary spherocytic anaemia and with distal renal tubular acidosis (dRTA). The molecular diagnosis of AE1 mutations has been complicated by the absence of highly polymorphic genetic markers, and the pathogenic mechanisms of some dRTA-associated AE1 mutations remain unclear. Here, we characterized a polymorphic dinucleotide repeat close to the human AE1 gene and performed an immunocytochemical study of kidney tissue from a patient with inherited dRTA with a defined AE1 mutation. METHODS: One CA repeat region was identified in a phage P1-derived artificial chromosome (PAC) clone containing most of the human AE1 gene and the upstream flanking region. We determined its heterozygosity value in multiple populations by PCR analysis. Genotyping of one family with dominant dRTA identified the AE1 R589H mutation, and family member genotypes were compared with the CA repeat length. AE1 and vH(+)-ATPase polypeptides in kidney tissue from an AE1 R589H patient were examined by immunocytochemistry for the first time. RESULTS: This CA repeat, previously reported as D17S1183, is approximately 90 kb upstream of the AE1 gene and displayed considerable length polymorphism, with small racial differences, and a heterozygosity value of 0.56. The allele-specific length of this repeat confirmed co-segregation of the AE1 R589H mutation with the disease phenotype in a family with dominant dRTA. Immunostaining of the kidney cortex from one affected member with superimposed chronic pyelonephritis revealed vH(+)-ATPase-positive intercalated cells in which AE1 was undetectable, and proximal tubular epithelial cells with apparently enhanced apical vH(+)-ATPase staining. CONCLUSIONS: The highly polymorphic dinucleotide repeat adjacent to the human AE1 gene may be useful for future studies of disease association and haplotype analysis. Intercalated cells persist in the end-stage kidney of a patient with familial autosomal dominant dRTA associated with the AE1 R589H mutation. The absence of detectable AE1 polypeptide in those intercalated cells supports the genetic prediction that the AE1 R589H mutation indeed causes dominant dRTA. 相似文献
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Emilie Balasse Gregory Gatouillat Dominique Patigny Marie Christine Andry Claudie Madoulet 《Vaccine》2009
Malignant melanoma causes significant health problems. The identification of tumour-associated antigens has led to novel approaches to increase T cell mediated anti-tumour immune response. Melan-A/MART-1 has been use as target antigen for several T cell based immunotherapeutic treatments. More recently, the critical role of CD4+ T cells in inducing and maintaining anti-tumour immunity has been increasingly recognized. In order to optimize tumour immunotherapy, greater efforts have been concentrated on the identification of tumour antigens presented by MHC class II molecules to CD4+ T cells. In a publication, Tiwari et al. (2004) [1] have identified by a computational approach the 15-mer amino-acid sequence 101–115 (PPAYEKLSAEQSPPP) of the Melan-A/MART-1 as a good target for a vigorous and safe immunotherapy. Therefore, we have investigated the in vivo anti-tumour activity of this peptide in a murine melanoma model. For the prophylactic treatment, 20 μg or 50 μg peptide was subcutaneously injected in mice once a week during 3 weeks before tumour induction. Treatment with 50 μg peptide significantly affected tumour development. Thus, our preliminary data demonstrate potential in vivo prophylactic activity of the 101–115 peptide-based vaccine to control melanoma growth. 相似文献
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Results of the Ross operation in a pediatric population 总被引:1,自引:0,他引:1
Mark G. Hazekamp Heynric B. Grotenhuis Paul H. Schoof Marie E.B. Rijlaarsdam Jaap Ottenkamp Robert A.E. Dion 《European journal of cardio-thoracic surgery》2005,27(6):975-979
Objective: To analyse the results of the mid-term clinical and echocardiographic follow-up of the pediatric Ross operation. Methods: Echo-Doppler follow-up of 53 consecutive pediatric Ross procedures performed between 1994 and 2003. Median age was 9.7 years at time of operation (2 weeks–17.7 years). Six patients were younger than 3 months. Median age at follow-up was 15.6 years. Aortic valve/left ventricular outflow tract (LVOT) anomalies were congenital in 49 (92%). Seventy percent had previous surgery or balloon valvuloplasty. Root replacement was used in all. Thirteen patients (25%) had LVOT enlargement. Mean cross-clamp time was 113 (69–189) minutes. Results: Early mortality occurred in 3 patients after emergency surgery following balloon failure (n=1) and extended Ross following interrupted arch/VSD repair (n=2). Late mortality was due to LV fibroelastosis in 2 patients and complicated pulmonary artery stenting in another. RVOT reoperations were required because of late homograft obstruction in 2 patients and because of pulmonary artery stenosis in another. Five patients (9.4%) were reoperated for pulmonary autograft dilatation (n=3) and for leaflet fibrosis or perforation (n=2). Autografts were repaired in two patients, while a mechanical valve was inserted in 3 cases. At 9 years the actuarial survival and event free survival were 89 and 74%, respectively. At last follow-up 90% of autograft diameters indexed to body surface area was above the 90th percentile of normal aortic root diameters. LVOT and RVOT gradients were low and autograft insufficiency was trivial to mild in 84% and mild to moderate in 16%. Autograft stenosis was not noticed. Conclusions: The pediatric Ross procedure remains an important tool but autograft dilatation also occurs in the pediatric population. The significance of this finding has yet to be determined. 相似文献
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Sukal Sean A. MD PhD † Tudisco Marie HT † Strippoli Barbara HT † Nehal Kishwer S. MD † 《Dermatologic surgery》2005,31(7):763-766
Background Processing multiple tissue sections in large Mohs cases is time consuming and labor intensive.
Objective To present innovative laboratory techniques to facilitate processing of large Mohs cases.
Methods A method for processing a large dermatofibrosarcoma protuberans Mohs case is outlined.
Results Modifications in tissue processing and equipment employed in a large Mohs case are presented.
Conclusion Innovative modifications to the standard Mohs laboratory technique can facilitate processing of large Mohs cases, resulting in high-quality, rapid frozen sections while optimizing efficiency. 相似文献
Objective To present innovative laboratory techniques to facilitate processing of large Mohs cases.
Methods A method for processing a large dermatofibrosarcoma protuberans Mohs case is outlined.
Results Modifications in tissue processing and equipment employed in a large Mohs case are presented.
Conclusion Innovative modifications to the standard Mohs laboratory technique can facilitate processing of large Mohs cases, resulting in high-quality, rapid frozen sections while optimizing efficiency. 相似文献
50.
George Lourenço PhD Sabine Meunier MD PhD Marie Vidailhet MD PhD Marion Simonetta‐Moreau MD PhD 《Movement disorders》2007,22(4):523-527
A decrease of heteronymous median nerve-evoked inhibition of corticospinal projections to forearm extensor muscles was reported in a group of 10 dystonic patients by Bertolasi and colleagues in 2003. Here we tested the excitability of corticomotoneuronal connections to both wrist extensor (ECR) and flexor (FCR) muscles after conditioning stimulation of median and also radial nerve at rest in a group of 25 patients with focal hand dystonia compared to 20 healthy subjects. We also investigated the effect of the wrist dystonic posture, either in flexion or in extension, on the afferent modulation of ECR and FCR motor evolved potentials (MEPs). The heteronymous (median-induced) but also homonymous (radial-induced) inhibitions (interstimuli intervals 13-21 ms) of ECR MEP size observed in healthy subjects were decreased in patients. In addition, homonymous (median-induced) facilitation of FCR MEP size was also decreased in patients while heteronymous inhibition (radial-induced) was not. Neither the involvement of the target muscle in the dystonic posture nor the origin of the afferent volley (from a dystonic muscle) influenced the degree of impairment of afferent modulation of the MEP. These findings support the view that a global abnormal somatosensory coupling in focal hand dystonia may contribute to an inadequate motor command to wrist muscles. 相似文献