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V. JNSSON H. D. SCHRDER W. TROJABORG T. STAEHELIN JENSEN E. HIPPE M. MRK HANSEN 《Journal of internal medicine》1992,232(2):185-191
A study of 17 patients with autoimmune axonal or demyelinating peripheral neuropathy in combination with M-component is described. The M-component was associated with MGUS (monoclonal gammopathy of undetermined significance) in 12 patients, CLL in one patient, WaldenstrÖm's disease in one patient, and myeloma in three patients. Immunohistological examination with direct and indirect fluorescence showed binding of antibodies to nerve structures of the same class and light chain as seen in the M-component. In five cases of IgM M-component, the demyelinating neuropathy was caused by binding of the IgM M-protein and complement C3b to myelin-associated glycoproteins (MAG). In 12 cases with axonal neuropathy, binding of IgG to the connective tissue of the peri- and endoneurium was found in 50% of cases, IgM in five cases, and IgD in one case. None of the patients had central nervous system (CNS) symptoms. The clinical and therapeutic difficulties are discussed; only two patients with an acute course responded to immunosuppression. A marked co-expression of other autoimmune phenomena is interpreted in the light of cross-reactions between the autoantibody and similar tissue autoantigens. 相似文献
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Sandford R; Sgotto B; Aparicio S; Brenner S; Vaudin M; Wilson RK; Chissoe S; Pepin K; Bateman A; Chothia C; Hughes J; Harris P 《Human molecular genetics》1997,6(9):1483-1489
PKD1 is the major locus of the common genetic disorder autosomal dominant
polycystic kidney disease (ADPKD). Analysis of the predicted protein
sequence of the human PKD1 gene, polycystin, shows a large molecule with a
unique arrangement of extracellular domains and multiple putative
transmembrane regions. The precise function of polycystin remains unclear
with a paucity of mutations to define key structural and functional
domains. To refine the structure of this protein we have cloned the genomic
region encoding the Fugu PKD1 gene. Fugu PKD1 spans 36 kb of genomic DNA
and has greater complexity with 54 exons compared with 46 in man.
Comparative analysis of the predicted protein sequences shows a lower level
of homology than in similar studies with identity of 40 and 59% similarity.
However key structural motifs including leucine rich repeats (LRR), a
C-type lectin and LDL-A like domains and 16 PKD repeats are maintained. A
region of homology with the sea urchin REJ protein was also confirmed in
Fugu but found to extend over 1000 amino acids. Several highly conserved
intra- and extra- cellular regions, with no known sequence homologies, that
are likely to be of functional importance were detected. The likely
structure of the membrane associated region has been refined with
similarity to the PKD2 protein and voltage gated Ca2+ and Na+ channels
highlighted over part of this area. The overall protein structure has
therefore been clarified and this comparative analysis derived structure
will form the basis for the functional study of polycystin and its
individual domains.
相似文献
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Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with beta-amyloid 总被引:6,自引:0,他引:6
Cribbs DH Ghochikyan A Vasilevko V Tran M Petrushina I Sadzikava N Babikyan D Kesslak P Kieber-Emmons T Cotman CW Agadjanyan MG 《International immunology》2003,15(4):505-514
The role of adjuvant on the T(h)1 and T(h)2 immune responses to Abeta-immunotherapy (Abeta(42 )peptide) was examined in wild-type mice. Fine epitope analysis with overlapping oligomers of the Abeta(42) sequence identified the 1-15 region as a dominant B cell epitope. The 6-20 peptide was recognized only weakly by antisera from mice administrated with Abeta(42) peptide formulated in complete Freund's adjuvant (CFA), alum or TiterMax Gold (TMG). However, mice immunized with Abeta(42) mixed with QS21 induced a significant antibody response to the 6-20 peptide. The only T cell epitope found was within the 6-28 sequence of Abeta(42). QS21 and CFA induced the strongest humoral response to Abeta, alum was intermediate, and TMG the weakest adjuvant. Analysis of antibody isotypes specific for Abeta indicates that alum induces primarily T(h)2-type immune response, whereas TMG, CFA and QS21 shift the immune responses toward a T(h)1 phenotype. Stimulation of splenocytes from Abeta-immunized mice with Abeta(40) peptide induced strikingly different cytokine expression profiles. QS21 and CFA induced significant IFN-gamma, IL-4 and tumor necrosis factor-alpha expression, whereas alum induced primarily IL-4 production. As T(h)1-type immune responses have been implicated in many autoimmune disorders, whereas T(h)2-type responses have been shown to inhibit autoimmune disease, the choice of adjuvant may be critical for the design of a safe and effective immunotherapy for Alzheimer's disease. 相似文献
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Pediatric health screening procedures, both prenatal and postnatal, have a tremendous potential in improving the health status of children and in turn reducing the resource burden on the parents and the State. The existing recommendations, inherent problems and different screening procedures are discussed. The need for suitable mass screening pediatric procedures in the Indian context is stressed.KEY WORDS: Pediatric screening procedures 相似文献
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In transgenic models of Alzheimer's disease (AD) neuronal loss has not been widely observed. The loss of neurons in AD may be due to chronic activation of complement (C') by beta-amyloid (A beta). A beta has been shown to activate C' by binding to a site on the C1q A-chain. The mouse A-chain sequence differs significantly from human, and a peptide based on the mouse A-chain sequence was ineffective at blocking activation of C' by A beta in contrast to the inhibition seen with the human peptide. Comparison of mouse and human serum showed that human C' was activated more effectively by A beta than was mouse C'. Therefore, additional genetic manipulations may be necessary to replicate in the murine model the inflammation and neurodegeneration that occur in AD. 相似文献
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The lateral magnocellular nucleus of the anterior neostriatum (lMAN) is necessary for both initial learning of vocal patterns in developing zebra finches, as well as for modification of adult song under some circumstances. Lateral MAN is composed of two subregions: a core of magnocellular neurons and a surrounding shell composed primarily of parvocellular neurons. Neurons in lMAN(core) project to a region of motor cortex known as robust nucleus of the archistriatum (RA), whereas neurons in lMAN(shell) project to a region adjacent to RA known as dorsal archistriatum (Ad). We studied the axonal connections of Ad in adult male zebra finches. In contrast to RA, Ad neurons make a large number of efferent projections, which do not include direct inputs to vocal or respiratory motor neurons. The major efferent projections of Ad are to: (1) the striatum of avian basal ganglia; (2) a dorsal thalamic zone (including the song-control nuclei dorsomedial nucleus of the posterior thalamus [DMP] and dorsolateral nucleus of the medial thalamus [DLM]); (3) restricted regions within the lateral hypothalamus (stratum cellulare externum [SCE]), which may also relay information to the same dorsal thalamic zone; (4) a nucleus in the caudal thalamus (medial spiriform nucleus [SpM]); (5) deep layers of the tectum, which project to the thalamic song-control nucleus Uva; (6) broad regions of pontine and midbrain reticular formation; and (7) areas within the ventral tegmental area and substantia nigra (ventral tegmental area [AVT], substantia nigra [SN]), which overlap with regions that project to Area X, a song-control nucleus of avian striatum. Inputs to Ad derive not only from lMAN(shell), but also from a large area of dorsolateral caudal neostriatum (dNCL), which also receives input from lMAN(shell). That is, lMAN(shell) neurons project directly to Ad, and also multisynaptically to Ad via dNCL. Double-labeling studies show that lMAN(shell) contains two different populations of projection neurons: one that projects to Ad and another to dNCL. These results are exciting for two main reasons. The first is that some of these projections represent potential closed-loop circuits that could relay information back to song-control nuclei of the telencephalon, possibly allowing diverse types of song-related information to be both integrated between loops and compared during the period of auditory-motor integration. Because both auditory experience with an adult (tutor) song pattern and auditory feedback are essential to vocal learning, closed-loop pathways could serve as comparator circuits in which efferent commands, auditory feedback, and the memory of the tutor song are compared in an iterative fashion to achieve a gradual refinement of vocal production until it matches the tutor song. In addition, these circuits seem to have a strong integrative and limbic flavor. That is, the axonal connections of Ad neurons clearly include regions that receive inputs not only from somatosensory, visual, and auditory areas of cortex, but also from limbic regions, suggesting that they may be involved in higher order sensory processing, arousal, and motivation. 相似文献