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Chain Gene (chain + gene)
Kinds of Chain Gene Terms modified by Chain Gene Selected AbstractsSuccessful Hepatorenal Transplantation in Hereditary Amyloidosis Caused by a Frame-Shift Mutation in Fibrinogen A,-Chain GeneAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2006C. Mousson Hereditary systemic amyloidosis comprises several autosomal dominant diseases caused by mutations in a number of plasma proteins, including the fibrinogen A,-chain. Four mutations in the fibrinogen A,-chain that are able to induce amyloidosis have been identified so far, the most common being the Glu526Val mutation. We have observed a family in which the father and his son reached end-stage renal failure because of renal amyloidosis induced by a frame-shift mutation in the fibrinogen A,-chain gene producing a novel amyloid protein. Two kidney transplantations in the father and one in the son resulted in fast graft loss caused by recurrence of amyloid deposition. We then performed hepatorenal transplantation in the son. Three years later, liver and kidney functions are normal without recurrence of amyloid deposition. This case, together with three others with the Glu526Val mutation in the extensive literature, suggests that liver transplantation can cure hereditary fibrinogen amyloidosis, whatever the mutation may be. [source] Further studies on knockout mice lacking a functional dynein heavy chain (MDHC7).CYTOSKELETON, Issue 2 2005Abstract Male mice had been previously generated in which the inner dynein arm heavy chain 7 gene (MDHC7) was disrupted. MDHC7,/, animals show asthenozoospermia and are sterile. Very few of their spermatozoa can achieve forward progression, but for those that can, we add here the information (1) that the three-dimensional aspects of their movement are normal; (2) that their maximum velocity is less than that of wild-type controls; and (3) that they are entirely unable to penetrate media of raised viscosity (25,4,000 cP). However, the large majority of the spermatozoa can achieve only a low amplitude vibration. In these sperm we find, using electron microscopy, that the outer dense fibres retain attachments to the inner surface of the mitochondria. Such attachments are present in normal epididymal mouse spermatozoa but are broken down as soon as the sperm become motile on release from the epididymis. The attachments are presumed to be essential during midpiece development and, afterwards, to require a threshold level of force to loosen them and so permit the sliding displacements necessary for normal bending. We presume that the disruption of the inner dynein arm heavy chain gene, MDHC7, means that there is insufficient force to overcome the attachments, for all but a few spermatozoa. Cell Motil. Cytoskeleton 61:74,82, 2005. © 2005 Wiley-Liss, Inc. [source] Electrophoretic variants of cardiac myosin heavy chain-, in Sprague Dawley ratsELECTROPHORESIS, Issue 3 2004Peter J. Reiser Abstract Analysis of cardiac myosin revealed differences in gel electrophoretic migration patterns of the ,-isoform of myosin heavy chain, but not the ,-isoform, in Sprague Dawley rats. No differences in the migration patterns of the ,-or ,-isoforms were observed in other rat strains. Three electrophoretic migration patterns of the ,-isoforms were observed in individual rats: a slower migrating isoform alone (4% of all rats tested), a faster migrating isoform alone (55%), and both isoforms (41%). The isoform expression pattern was identical in all myocardial regions in each rat. Frequency of expression patterns suggests multiple gene sequences for ,-cardiac myosin heavy chain in Sprague Dawley rats. Sequence analysis of amplified regions of the Sprague Dawley and Brown Norway rat ,-myosin genes, specifically the 5'-untranslated region, exons 1,3, and associated introns, showed numerous single nucleotide polymorphisms in coding and noncoding regions, including putative regulatory sites in Sprague Dawley rats, but not in Brown Norway rats. All Sprague Dawley rats varied from Brown Norway rats and no heterogeneity was observed in Brown Norway rats. Several deletions and dimorphic positions were also observed. Dimorphic positions were evident on automated sequencing comparisons. The data indicate that at least two ,-myosin heavy chain isoforms exist in Sprague Dawley rats and these rats exhibit sequence diversity within that portion of the ,-myosin heavy chain gene reported in this study. [source] Assessment of peripheral blood lymphocyte subsets in idiopathic myelofibrosisEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2000Francisco Cervantes Abstract: The objective of this study was to contribute to a better characterization of the immunological profile of idiopathic myelofibrosis (IM) at presentation by analysing the blood lymphocyte subsets and their possible correlations with other disease features. Absolute blood lymphocytes and lymphocyte subsets were assessed in 31 IM patients, compared with those from 34 healthy individuals, and correlated with the patients' main clinical, hematological and bone marrow histologic features. The mean lymphocyte count of the IM patients was 1.1 (SD 0.6)×109/L, versus 1.6 (SD 0.49)×109/L in controls (p=0.0006), with 24 of the 31 patients (77.4%) showing lymphocytopenia (<1.5×109/L). IM patients had significantly lower counts of CD3, CD4, CD8, and CD3,/CD56+ cells, and significantly higher CD3+/CD56+ lymphocyte counts. Although no significant differences were found between patients and controls with regard to CD19+/CD5+ cell counts, increased CD5+ B-cell lymphocytes were observed in three IM patients. In one of the latter patients, Ig gene rearrangement analysis of the heavy chain gene demonstrated such a subpopulation to be clonal, but the patient did not develop features of chronic lymphoid leukemia during a 5-yr follow-up. No correlation was found between the patients' blood lymphocyte counts and other disease features. We conclude that most IM patients have absolute lymphopenia, decreased T cells and increased cytotoxic T cells at diagnosis, and 10% of them show an increased CD5+ B-cell subpopulation. [source] Non-muscle myosin heavy chain (MYH9): A new partner fused to ALK in anaplastic large cell lymphomaGENES, CHROMOSOMES AND CANCER, Issue 4 2003Laurence Lamant In anaplastic large cell lymphoma, the ALK gene at 2p23 is known to be fused to NPM, TPM3, TPM4, TFG, ATIC, CLTC, MSN, and ALO17. All of these translocations result in the expression of chimeric ALK transcripts that are translated into fusion proteins with tyrosine kinase activity and oncogenic properties. We report a case showing a restricted cytoplasmic staining pattern of ALK and a novel chromosomal abnormality, t(2;22)(p23;q11.2), demonstrated by fluorescence in situ hybridization analysis. The result of 5, RACE analysis showed that the ALK gene was fused in-frame to a portion of the non-muscle myosin heavy chain gene, MYH9. Nucleotide sequence of the MYH9-ALK chimeric cDNA revealed that the ALK breakpoint was different from all those previously reported. It is localized in the same exonic sequence as MSN-ALK, but 6 bp downstream, resulting in an in-frame fusion of the two partner proteins. In contrast to the previously reported ALK fusion proteins, MYH9-ALK may lack a functional oligomerization domain. However, biochemical analysis showed that the new fusion protein is tyrosine phosphorylated in vivo but seems to lack tyrosine kinase activity in vitro. If further investigations confirm this latter result, the in vivo tyrosine phosphorylation of MYH9-ALK protein could involve mechanisms different from those described in the other ALK hybrid proteins. © 2003 Wiley-Liss, Inc. [source] Cd8+/v,5.1+ large granular lymphocyte leukemia associated with autoimmune cytopenias, rheumatoid arthritis and vascular mammary skin lesions: successful response to 2-deoxycoformycin.HEMATOLOGICAL ONCOLOGY, Issue 2 2002E. Granjo Abstract We report a case of CD8+/V,5.1+ T-cell large granular lymphocyte leukemia (T-LGL leukemia) presenting with mild lymphocytosis, severe autoimmune neutropenia, thrombocytopenia, polyarthritis and recurrent infections with a chronic disease course. Immunophenotyping showed an expansion of CD3+/TCR,,+/CD8+bright/CD11c+/CD57,/CD56, large granular lymphocytes with expression of the TCR-V,5.1 family. Southern blot analysis revealed a clonal rearrangement of the TCR ,-chain gene. Hematopoietic growth factors, high dose intravenous immunoglobulin and corticosteroids were of limited therapeutic benefit to correct the cytopenias. During the disease course, the patient developed a severe cutaneous leg ulcer and bilateral vascular mammary skin lesions. Treatment with 2-deoxycoformycin resulted in both clinical and hematological complete responses, including the resolution of vascular skin lesions. Combined immuno-staining with relevant T-cell associated and anti-TCR-V, monoclonal antibodies proved to be a sensitive method to assess the therapeutic effect of 2-deoxycoformicin and to evaluate the residual disease. Copyright © 2002 John Wiley & Sons, Ltd. [source] An intron enhancer activates the immunoglobulin-related Hemolin gene in Hyalophora cecropiaINSECT MOLECULAR BIOLOGY, Issue 5 2002K. Roxström-Lindquist Abstract Hemolin is the only insect member of the immunoglobulin (Ig) superfamily reported to be up-regulated during an immune response. In diapausing pupae of Hyalophora cecropia the gene is expressed in fat body cells and in haemocytes. Like the mammalian Ig , light chain gene, the Hemolin gene harbours an enhancer including a ,B motif in one of its introns. This motif binds the H. cecropia Rel factor Cif (Cecropia immunoresponsive factor). The Hemolin third intron also mediates transient reporter gene expression in immunoresponsive Drosophila mbn-2 cells. Co-transfections of Drosophila SL2 cells showed that the Drosophila Rel factor Dif (Dorsal-related immunity factor), transactivates reporter gene constructs through the intron. Moreover, a 4.8-fold synergistic activation was obtained when Dif is combined with the rat C/EBP (CCAAT/enhancer element-binding protein) and human HMGI (high mobility group protein I). This is the first report of an insect immune-related gene that is up-regulated by an enhancer activity conferred through an intron. [source] The value of molecular analysis by PCR in the diagnosis of cutaneous lymphocytic infiltratesJOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2002Niels Holm The diagnosis and classification of cutaneous lymphomas remain a challenge for the clinician and dermatopathologist. This diagnostic dilemma is mainly encountered in the distinction between an early malignant lymphoma and a benign reactive lymphocytic infiltrate (pseudolymphoma). Until the beginning of the 1980s, our diagnostic tools were limited to the clinical presentation, course, and histopathology in diagnosis and classification of lymphocytic infiltrates. Advances in immunology and, in particular, in molecular genetics with the introduction of the Southern blot technique and the polymerase chain reaction (PCR) have revolutionized the diagnosis of lymphocytic infiltrates by determination of clonality. In some series, more than 90% of cutaneous T-cell lymphomas have a clonal rearrangement of the T-cell receptor ,-chain gene, as opposed to very low percentages of rearrangement in T-cell pseudolymphomas. However, the presence of clonality does not necessarily imply malignancy. Cases of pseudolymphomas, lichen planus and pityriasis lichenoides et varioliformis acuta were reported with clonal lymphocytic proliferations. Therefore, care should be exercised in the evaluation of the results of molecular analysis, and these should always be correlated with the clinical, histological and immunophenotypic picture to arrive at the correct diagnosis. It may be expected that the molecular methods for diagnosis of lymphocytic infiltrates will be improved and refined in future, and that sensitivity and specificity will increase. [source] Large plaque parapsoriasis: clinical and genotypic correlationsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2000Martin Simon Twelve patients with large plaque parapsoriasis (LPP) were investigated for the presence of predominant T-cell clones, analyzing the T-cell receptor (TCR) ,-chain gene. The diagnostic and prognostic significance of TCR gene rearrangement status was assessed by a correlation with the long-term clinical follow-up. Six out of 12 patients showed a clonal T-cell population. Clinically, among the patients with clonal disease one developed clearcut mycosis fungoides (MF) after a follow-up of 8 years, in the other 5 patients no such diagnosis could be made after follow-up of 2,21 years (median: 9 years). In patients with polyclonal infiltrates the lesions remained virtually unchanged. These findings indicate that in LPP TCR gene rearrangement status has no prognostic significance and does not allow distinction of LPP and early MF. Both conditions show a clonal T-cell infiltrate with similar frequency, are very similar in clinical and histologic presentation and according to recent studies share the same low risk to develop overt MF. Therefore both terms refer to the identical clinical situation. This should be designated as early MF and efforts should concentrate on identifying those patients that are at risk to develop aggressive disease. [source] Are giant axons a pathological marker of charcot-marie-tooth neuropathy type 2E?JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004T Cavallaro Background: According to electrophysiological and pathological criteria Charcot Marie Tooth (CMT) disease includes primary demyelinating forms (CMT1) and neuropathies with primary axonal loss (CMT2). In CMT1, genetic analysis provided some associations between characteristic lesions and different proteins. In CMT2, four genes were identified recently (CMT2A, B, D, E); the molecular diagnosis is complex and phenotypical hallmarks are lacking. Objectives: To describe the nerve biopsy in three pedigrees with CMT2E caused by mutations of the neurofilament-light chain gene (NF-L): two pedigrees from Campania sharing a Pro22Ser substitution in the head domain of protein and one pedigree from Apulia with a novel Leu268Prol substitution in the central rod domain. In all three pedigrees electrophysiology was consistent with a mixed, demyelinating and axonal neuropathy. Results: The three patients analysed revealed a primary axonopathy characterized by giant axonal swelling filled with densely packed neurofilaments and some atrophic axons. Conclusions: We propose that, in the diagnostic work up of CMT2, giant axons may orientate towards CMT2E. The pathological alterations detected correlate intuitively with an altered function of the neurofilaments which constitute the axonal cytoskeleton and are critical for radial growth and for axonal transport. [source] Two novel fibrinogen variants found in patients with pulmonary embolism and their familiesJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2003M. M. L. Hanss Summary.,Background:,The occurrence of dysfibrinogen is quite rare in comparison with other hemostatic defects, specially in cases of venous thrombosis. Objectives:,Fibrinogen is known to have multiple functions, which are not evaluated by simple coagulation testing. We have used gel electrophoresis to search for new mutations. Patients and methods:,Specimens of purified fibrinogen from 217 consecutive patients with familial or recurrent or early thrombosis and from 490 control subjects were evaluated by electrophoresis. Plasma fibrinogen levels and coagulation-dependent tests (electromechanical and optical coagulometric determinations, immunological measurement, thrombin and Reptilase® times) were normal. Results:,Two novel familial variants were detected. For a 42-year-old patient, an in-frame 117 base pair insertion in the A,-chain gene caused a 5-kDa mobility shift of the A, chain. This corresponds to a 39 amino acid duplication in the connector domain (fibrinogen Champagne au Mont d'Or). This pattern was also found in the patient's mother and child. A second 31-year-old patient presented an extra band under non-reducing conditions, 30 kDa larger than HMW fibrinogen and reacting with antifibrinogen antibodies (fibrinogen Lozanne). A heterozygous 5909A,G mutation was found on the B,-chain gene leading to heterozygous B, Tyr236, stop codon. The predicted truncated B, chain could participate in chain assembly. Two family members were also affected, one of whom had suffered early venous thrombosis. Conclusions:,Electrophoretic testing of apparently normal fibrinogens can reveal new variants which may be clinically relevant. [source] Successful Hepatorenal Transplantation in Hereditary Amyloidosis Caused by a Frame-Shift Mutation in Fibrinogen A,-Chain GeneAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2006C. Mousson Hereditary systemic amyloidosis comprises several autosomal dominant diseases caused by mutations in a number of plasma proteins, including the fibrinogen A,-chain. Four mutations in the fibrinogen A,-chain that are able to induce amyloidosis have been identified so far, the most common being the Glu526Val mutation. We have observed a family in which the father and his son reached end-stage renal failure because of renal amyloidosis induced by a frame-shift mutation in the fibrinogen A,-chain gene producing a novel amyloid protein. Two kidney transplantations in the father and one in the son resulted in fast graft loss caused by recurrence of amyloid deposition. We then performed hepatorenal transplantation in the son. Three years later, liver and kidney functions are normal without recurrence of amyloid deposition. This case, together with three others with the Glu526Val mutation in the extensive literature, suggests that liver transplantation can cure hereditary fibrinogen amyloidosis, whatever the mutation may be. [source] Incorporation of fibrin molecules containing fibrinopeptide A alters clot ultrastructure and decreases permeabilityBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2007Veronica H. Flood Summary Previous studies have shown that a heterozygous mutation in the fibrinogen A, chain gene, which results in an A, R16C substitution, causes fibrinolytic resistance in the fibrin clot. This mutation prevents thrombin cleavage of fibrinopeptide A from mutant A, R16C chains, but not from wild-type A, chains. However, the mechanism underlying the fibrinolytic resistance is unclear. Therefore, this study investigated the biophysical properties of the mutant fibrin that contribute to fibrinolytic resistance. Fibrin clots made from the mutant fibrinogen incorporated molecules containing fibrinopeptide A into the polymerised clot, which resulted in a ,spiky' clot ultrastructure with barbed fibrin strands. The clots were less stiff than normal fibrin and were cross-linked slower by activated FXIII, but had an increased average fiber diameter, were more dense, had smaller pores and were less permeable. Protein sequencing showed that unclottable fibrinogen remaining in the supernatant consisted entirely of homodimeric A, R16C fibrinogen, whereas both cleaved wild-type , chains and uncleaved A, R16C chains were in the fibrin clot. Therefore, fibrinolytic resistance of the mutant clots is probably a result of altered clot ultrastructure caused by the incorporation of fibrin molecules containing fibrinopeptide A, resulting in larger diameter fibers and decreased permeability to fibrinolytic enzymes. [source] Developmental expression and comparative genomic analysis of Xenopus cardiac myosin heavy chain genesDEVELOPMENTAL DYNAMICS, Issue 4 2005Robert J. Garriock Abstract Myosin heavy chains (MHC) are cytoskeletal motor proteins essential to the process of muscle contraction. We have determined the complete sequences of the Xenopus cardiac MHC genes, ,-MHC and ventricular MHC (vMHC), and have characterized their developmental expression profiles. Whereas ,-MHC is expressed from the earliest stages of cardiac differentiation, vMHC transcripts are not detected until the heart has undergone chamber formation. Early expression of vMHC appears to mark the cardiac conduction system, but expression expands to include the ventricle and outflow tract myocardium during subsequent development. Sequence comparisons, transgenic expression analysis, and comparative genomic studies indicate that Xenopus ,-MHC is the true orthologue of the mammalian ,-MHC gene. On the other hand, we show that the Xenopus vMHC gene is most closely related to chicken ventricular MHC (vMHC1) not the mammalian ,-MHC. Comparative genomic analysis has allowed the detection of a mammalian MHC gene (MyH15) that appears to be the orthologue of vMHC, but evidence suggests that this gene is no longer active. Developmental Dynamics 233:1287,1293, 2005. © 2005 Wiley-Liss, Inc. [source] Clonally rearranged T-cell receptor , chain genes in HTLV-I carriers with abnormal, non-flower-like, lymphocytesEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2005Maria M. Sales Abstract:,Background:,The diagnosis of Adult T-cell leukemia/lymphoma ATLL subtypes in human T-lymphotropic virus type I (HTLV-I) carriers based in morphology and immunophenotype of lymphocytes can be challenger. We propose that polymerase chain reaction (PCR) amplification of the rearranged TCR gene in HTLV-I healthy carriers would be a convenient method for establishing the nature of the circulating T lymphocytes in asymptomatic HTLV-I carriers, presenting only mild and inconclusive signals of deviation from normality. Methods:,Using PCR, we analyzed the genetic recombination pattern of the T-cell , -chain receptor gene (TCR - ,) in order to identify clonal expansion of peripheral blood T lymphocytes in 17 HTLV-I-positive healthy carriers and in nine normal HTLV-I-negative blood donors. To evaluate the performance of PCR in detection of clonality, we also analyzed 18 patients with post-thymic/mature T-cell malignancies presenting circulating abnormal lymphocytes. Results:,Seven of the 17 HTLV-I positive individuals presented circulating abnormal lymphocytes; monoclonal or oligoclonal expansion of T-cells was detected in five of the 17 HTLV-I-positive individuals, all of them presenting abnormal lymphocytes. Clonal expansion was not detected in any of the negative controls or in any of the 12 remaining healthy carriers. All patients in the positive control group tested positive by PCR and Southern blots. Southern blots were negative for all 17 healthy carriers. Conclusions:,PCR amplification of segments of rearranged TCR- , is reliable for allowing early detection of small populations of clonal T cells in blood samples from asymptomatic HTLV-I carriers, providing an additional alert in the follow-up of carriers with abnormal circulating lymphocytes. [source] Intra- and inter-allelic ordering of T cell receptor , chain gene assemblyEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2005Bernard Khor Abstract Allelic exclusion at the TCR, locus mandates that gene assembly be regulated in a manner that permits feedback inhibition of further complete TCR, rearrangements upon pre-TCR expression. Here we show that assembly of TCR, chain genes from V,, D, and J, gene segments is intra-allelically ordered, proceeding primarily through DJ,, and not VD,, intermediates. This ensures that V, to DJ, rearrangement, which can be feedback inhibited, is the final step in the assembly process. A newly assembled VDJ, rearrangement must be tested to determine if it is in-frame before V, to DJ, rearrangement is permitted on the alternate allele. This inter-allelic ordering may occur through a general inefficiency of V, to DJ, rearrangement and/or through static differences in accessibility of the two TCR, alleles. However, we find that within the regulatory context of allelic exclusion, V, to DJ, rearrangement proceeds to completion on both alleles. Furthermore, all possible VDJ, rearrangements are not completed on one allele before V, to DJ, rearrangement is initiated on the alternate allele. Together, these data support a dynamic model of inter-allelic accessibility that permits the ordered and efficient assembly of complete variable region genes on both TCR, alleles during T cell development. [source] Genetic organization of A chain and B chain of ,-bungarotoxin from Taiwan banded krait (Bungarus multicinctus)FEBS JOURNAL, Issue 15 2000A chain genes, B chain genes do not share a common origin ,-Bungarotoxin, the main presynaptic neurotoxin purified from the venom of Bungarus multicinctus, consists of two dissimilar polypeptide chains, the A chain and the B chain, cross-linked by an interchain disulfide bond. In this study, A and B chain genes isolated from the liver of B. multicinctus encoded the A and B chain precursors, respectively. Analyses of the coding regions of the A and B chain genes revealed that both consist of three exons and two introns. The sequences of all exon/intron junctions agree with the GT/AG rule. However, sequence alignment and phylogenetic analysis did not support that the evolution of A and B chain genes are closely related. Comparative analysis of A chain genes with Viperinae and Crotalinae phospholipase A2 genes indicated that genetic divergence of the A chain and phospholipase A2s was in accordance with their family. Moreover, evolutionary divergence of the intron and exon regions of the A chain, as observed for phospholipase A2 genes, was not consistent. Noticeably, the transcription of A and B chain genes may be regulated under different transcription factors as revealed by analyses of their promoter sequences. In terms of the finding that A and B chains are encoded separately by different genes, this strongly supports the view that the intact ,-bungarotoxin molecules should be derived from the pairing of A and B chains after their mRNAs are translated. [source] High sensitivity of chemiluminescent methodology for detection of clonal CDR3 sequences in patients with acute lymphoblastic leukemiaHEMATOLOGICAL ONCOLOGY, Issue 2 2004E. Leal Abstract Detection of minimal residual disease (MRD) in patients with B-cell acute lymphoblastic leukemia (B-ALL) has been achieved using several radioactive labelling methodologies; however, limited information exists about the use of chemiluminescent labelling. Although many malignant disorders are related to cytogenetic alterations, there is not a consistent chromosomal translocation that could serve as a tumour marker for the monitoring of MRD. ALL are derived from B-lymphocytes in 80% of cases. In the early stages of their maturation, the immunoglobulin heavy chain genes (IgH) undergo rearrangements among their V, D, and J segments, giving rise to the Complementary Determining Regions (CDR). Among these, CDR3 is considered unique for each lymphocyte and used as a tumour-specific marker in B-ALL patients. In this study, the CDR3 was labelled with digoxigenin and used as a patient-specific probe to test its sensitivity for further detection of MRD. Fourteen pretreatment samples of bone marrow (BM) or peripheral blood (PB) from B-ALL patients were included. Tumour-specific probes were designed from each clonal product by elimination of the consensus sequences. Ten digoxigenin-labelled probes were hybridized with a mixture of their respective clonal DNA and the polyclonal product from a normal healthy donor, in serial dilutions from 1:1 up to 1:107. A sensitivity range of 1:103,1:106 was obtained, with an average of 1:105. Crossed tests performed in four patients, showed right probe specificity in all cases. We propose that the design of allele-specific probes with chemiluminescent labelling, represents a reliable, sure and sensitive alternative methodology for MRD detection in patients with B-cell lymphoproliferative disorders. Copyright © 2004 John Wiley & Sons, Ltd. [source] Regulation of immunoglobulin heavy-chain gene rearrangementsIMMUNOLOGICAL REVIEWS, Issue 1 2004Dipanjan Chowdhury Summary:, Regulated assembly of antigen receptor gene segments to produce functional genes is a hallmark of B- and T-lymphocyte development. The immunoglobulin heavy-chain (IgH) and T-cell receptor ,-chain genes rearrange first in B and T lineages, respectively. Both loci require two recombination events to assemble functional genes; D-to-J recombination occurs first followed by V-to-DJ recombination. Despite similarities in overall rearrangement patterns, each locus has unique regulatory features. Here, we review the characteristics of IgH gene rearrangements such as developmental timing, deletion versus inversion, DH gene segment utilization, ordered recombination of VH gene segments, and feedback inhibition of rearrangement in pre-B cells. We summarize chromatin structural features of the locus before and during recombination and, wherever possible, incorporate these into working hypotheses for understanding regulation of IgH gene recombination. The picture emerges that the IgH locus is activated in discrete, independently regulated domains. A domain encompassing DH and JH gene segments is activated first, within which recombination is initiated. VH genes are activated subsequently and, in part, by interleukin-7. These observations lead to a model for feedback inhibition of IgH rearrangements. [source] Acral pseudolymphomatous angiokeratoma of children: immunohistochemical and clonal analyses of the infiltrating cellsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 5 2002Yoshitaka Hagari Background:, Acral pseudolymphomatous angiokeratoma of children (APACHE) is a disorder characterized clinically by red nodules and histopathologically by a massive subepidermal lymphohistiocytic infiltrate. Although it was initially thought to be a vascular nevus, it has never been regarded as a pseudolymphoma. Case report: We report a 7-year-old-girl with small red nodules on the dorsum of the right foot and a 73-year-old man with asymptomatic brown-red nodules on the lower extremities. Results:, Histopathologic examination revealed a massive lymphohistiocytic infiltrate with plasma cells, some eosinophils, or a multinucleated giant cell immediately beneath the epidermis. Thick-walled vessels were observed in the infiltrate. These characteristics are identical to those of acral pseudolymphomatous angiokeratoma of children. The infiltrate was composed mainly of equal numbers of CD4+ or CD8+ T cells and equal numbers of B cells stained for , or , light chains. PCR amplification of rearranged immunoglobulin heavy chain genes or T-cell receptor , genes showed no evidence of clonality, suggesting that these infiltrates were polyclonal both for B and T cells. Conclusions:, Our data support the idea that this disorder represents a reactive process. The modified term ,papular angiolymphoid hyperplasia' would define this disorder more appropriately. [source] Two modes of mitochondrial dysfunction lead independently to lifespan extension in Caenorhabditis elegansAGING CELL, Issue 3 2010Wen Yang Summary In Caenorhabditis elegans, longevity is increased by a partial loss-of-function mutation in the mitochondrial complex III subunit gene isp-1. Longevity is also increased by RNAi against the expression of a variety of mitochondrial respiratory chain genes, including isp-1, but it is unknown whether the isp-1(qm150) mutation and the RNAi treatments trigger the same underlying mechanisms of longevity. We have identified nuo-6(qm200), a mutation in a conserved subunit of mitochondrial complex I (NUDFB4). The mutation reduces the function of complex I and, like isp-1(qm150), results in low oxygen consumption, slow growth, slow behavior, and increased lifespan. We have compared the phenotypes of nuo-6(qm200) to those of nuo-6(RNAi) and found them to be distinct in crucial ways, including patterns of growth and fertility, behavioral rates, oxygen consumption, ATP levels, autophagy, and resistance to paraquat, as well as expression of superoxide dismutases, mitochondrial heat-shock proteins, and other gene expression markers. RNAi treatments appear to generate a stress and autophagy response, while the genomic mutation alters electron transport and reactive oxygen species metabolism. For many phenotypes, we also compared isp-1(qm150) to isp-1(RNAi) and found the same pattern of differences. Most importantly, we found that, while the lifespan of nuo-6, isp-1 double mutants is not greater than that of the single mutants, the lifespan increase induced by nuo-6(RNAi) is fully additive to that induced by isp-1(qm150), and the increase induced by isp-1(RNAi) is fully additive to that induced by nuo-6(qm200). Our results demonstrate that distinct and separable aspects of mitochondrial biology affect lifespan independently. [source] Laminins and their roles in mammalsMICROSCOPY RESEARCH AND TECHNIQUE, Issue 5 2008Jeffrey H. Miner Abstract Laminins are ,-,-, heterotrimeric components of all basement membranes. Laminins are now known to play the central role in organizing and establishing the basement membrane. The diversity of laminins allows them to impart special structural and signaling properties to the basement membrane. Of the 12 known laminin chain genes, 10 have been either found to be mutated in humans or experimentally mutated in mice. This has led to great progress over the last several years towards understanding both the functions of laminins and the reasons for their great diversity. In this review, I will summarize the in vivo studies in mice and humans that have contributed to this new knowledge. Microsc. Res. Tech., 2008. © 2008 Wiley-Liss, Inc. [source] Richter syndrome in B-cell chronic lymphocytic leukemiaPATHOLOGY INTERNATIONAL, Issue 4 2003Naoya Nakamura Richter syndrome (RS) is well known as a secondary high-grade lymphoma, mostly diffuse large B-cell lymphoma (DLBCL) developed in patients with B-cell chronic lymphocytic leukemia (B-CLL). In this review, we describe clinicopathological, histological, immunophenotypical and genetic findings of RS. The patients with RS, regardless of transformation of pre-existing clone or de novo malignant clone, were resistant to conventional combined chemotherapy and died within months of diagnosis. Molecular techniques can provide convincing results for the clonal relationship of RS to pre-existing B-CLL. When RS carries a same rearrangement band or a same sequence as B-CLL by Southern blotting or nucleotide sequence analyses of immunoglobulin heavy and/or light chain genes, it is suggested to that RS transforms from original B-CLL. These analyses have showed that approximately two-thirds of RS cases evolved from a B-CLL clone. How and where does the B-CLL clone evolve to RS? The genetic alteration of transforming B-CLL clone into RS has been addressed. Abnormalities of chromosomes 11 and 14 were most frequently involved in RS, but non-specific. In addition, RS does not include chromosomal translocation between Ig locus and oncogenes or rearrangements of bcl-6 gene, both of which were found in some de novo DLBCL. Several candidates, such as mutation of p53 gene and abnormalities of cyclin dependent kinase inhibitor, have been proposed to play an important role in the transformation of a part of B-CLL. However, there is still uncertainly as to how B-CLL progresses or develops into RS. [source] cDNA cloning and genetic polymorphism of the swine major histocompatibility complex (SLA) class II DMA geneANIMAL GENETICS, Issue 2 2001A. Ando cDNA clones corresponding to the swine histocompatibility complex (SLA: swine leucocyte antigen)-DM , chain were isolated using the polymerase chain reaction (PCR) products from the third exon in the human HLA-DMA gene as a probe. Amino acid comparative analysis revealed that these clones were more closely related to the bovine and human DMA genes than to the other swine class II genes , chain genes, DRA, DQA and DOA. These results suggest that the SLA-DMA gene is expressed and may function, like HLA-DM, as an important modulator in class II restricted antigen processing in swine. Furthermore, based on the sequences and PCR,restriction fragment length polymorphism (PCR,RFLP) patterns in the SLA-DMA gene, no allelic variation was recognized in the second exon, but five allelic variations were recognized in the third exon in five different breeds of swine. These DMA alleles were defined by variation at four nucleotide positions. Two of these alleles resulted in an amino acid substitution. These results suggest that SLA-DMA has little polymorphism as observed in HLA-DMA and mouse H2-Ma. [source] | |||||||||||||||||||||||||