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31.
CD44 Isoform Expression Follows Two Alternative Splicing Pathways in Breast Tissue 总被引:1,自引:0,他引:1
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![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Xavier Roca Jos L. Mate Aurelio Ariza Ana M. Muoz-Mrmol Claudia von Uexküll-Güldeband Inmaculada Pellicer Jos J. Navas-Palacios Marcos Isamat 《The American journal of pathology》1998,153(1):183-190
The repertoire of distinct CD44 protein isoforms is generated by means of alternative pre-mRNA splicing of 10 variable exons located in the central region of the CD44 gene. We have used human breast ductal carcinoma as a model to identify two alternative splicing pathways of the CD44 pre-mRNA variable region that account for the generation of all of the CD44 isoforms described in breast tissue. An alternative splicing pathway that reflects inclusion of variable exons in a gradual 3′-to-5′ fashion is evidenced in breast ductal carcinoma and its lymph node metastases. This pathway is compatible with a mechanism that generates the standard form of CD44 (devoid of variable exons) and is distinguishable from an alternative splicing pathway that involves exclusively variant exon 3 and is observable in both normal and carcinoma breast tissue. We show that both pathways are detectable in the same cell type in the breast and provide a speculative model by which these splicing routes could take place. 相似文献
32.
In recent reports we described novel hybridization patterns (HP) corresponding to 22 potentially new HLA-B locus alleles in a panel of 547 subjects studied by PCR-SSOP. Three of them correspond to new subtypes of B35. To confirm the hybridization results we have isolated DNA from PBL and performed PCR, DNA cloning and nucleotide sequencing. One of the alleles, locally called B-3505v was found in three individuals: two Hispanic, one Caucasoid. It differs from B*3505 by 3 nucleotide substitutions that lead to changes in residues 94 (Ile > Thr), 95 (Ile > Leu) and 103 (Val > Leu). B-3505v differs from B*3501 in residues 97 and 103. Another allele called B-3508v, was found in 7 individuals, (6 of 122 Toba Indians, 1 of 18 Pilaga Indians). It differs from B*3509 in two silent nucleotide substitutions (codons 135 and 138) and in one substitution in residue 156 (Arg > Leu). The new allele has a hybrid sequence between B* 3508 and B*4801. A third subtype, locally called B-3504v, observed in two Hispanic individuals, is identical to B*3512. B*3512 differs from B*3504 by 3 nucleotides and one amino acid. Substitutions in residue 95 contribute to the structure of specificity pocket F, 97 to C and E, and 156 to pockets D and E. Therefore it is possible that some of the new alleles may have different peptide binding profiles. Since differences in residue 156 have been shown to affect allorecognition and mediate GvHD, identification of such variants may have important implications in transplantation and perhaps in studies of immune responses to peptides and pathogens. 相似文献
33.
Enhanced molecular volume of conservatively pegylated Hb: (SP-PEG5K)6-HbA is non-hypertensive 总被引:2,自引:0,他引:2
Acharya SA Friedman JM Manjula BN Intaglietta M Tsai AG Winslow RM Malavalli A Vandegriff K Smith PK 《Artificial cells, blood substitutes, and immobilization biotechnology》2005,33(3):239-255
Recent studies have suggested that the "pressor effect" of acellular Hb is a consequence of perturbation of the macro-and microcirculatory system in multiple ways, and that PEGylation is an effective approach for controlling the same. In an attempt to confirm this concept, a new and simple thiolation mediated, maleimide chemistry-based conservative PEGylation protocol has been developed to conjugate multiple copies of PEG-chains to Hb. This approach combines the high reactivity of maleimides towards thiols with the propensity of iminothiolane to derivatize the epsilon-amino groups of proteins into reactive thiol groups, with conservation of their positive charge. One of the PEGylated products, namely (SP-PEG5K)6-HbA, that carries on an average six copies of PEG5000 chains per Hb, is non-hypertensive in hamster top load and in rat 50% exchange transfusion models. This hexa-PEGylated-Hb has (i) a hydrodynamic volume corresponding to that of an oligomerized Hb of 256kDa, (ii) a molecular radius of approximately 6.8 nm, (iii) high oxygen affinity, (iv) lowered Bohr effect, and (v) increased viscosity and colloidal osmotic pressure. These properties of (SP-PEG5K)6-HbA are consistent with the emerging new paradigms for the design of Hb based oxygen carriers and confirm the concept that the "pressor effect" of Hb is a multifactorial event. The thiolation mediated maleimide chemistry-based PEGylation protocol described here for the generation of (SP-PEG5K)6-Hb is simple, highly efficient, and is carried out under oxy conditions. The results demonstrate that a non-hypertensive PEG-Hb can be generated by conjugation of a lower number of PEG chains than previously reported. 相似文献
34.
Antikinetochore antibodies and fluorescence in situ hybridizationwith an alphoid centromeric probe were applied to the cytokinesis-blockmicronucleus (MN) assay to study the suitability of these methodologiesto detect clastogenic/aneugenic activity in isolated human lymphocytes.The chemicals selected for this study were the herbicide alachlor,the clastogen mitomycin-C (MMC), and the aneugen vinblastinesulphate (VBL). Futhermore, MN frequencies obtained from slidesstained with MayGrünwaldGiemsa (MGG) andwith the DNA fluorochrome 4', 6'diamidino-2-phenylindole (DAPI)were compared to check if the DNA-specific DAPI facilitateda more accurate recording of MN than the unspecific MGG. Theresults showed that the detection of kinetochores (KC) or centromeres(CM) within MN are equally reliable and sensitive techniquesto study the mode of action of clastogenic and aneugenic agents.The comparison of CM and KC detection in control cultures suggestedthat up to 17% of spontaneous chromosomecontaining MN may bedue to KC disruption, whereas the majority are caused by dysfunctionin other components of the mitotic apparatus. Alachlor (7.520µg/ml) and MMC (0.6 µM) acted as pure clastogenswithout aneugenic activity, inducing exclusively KC- and CM-negativeMN. VBL produced primarily KC- and CM-positive MN, in accordancewith its known mechanism of action. A comparison between CMand KC data in the VBL treatment suggested that some 7% of KC-containingMN may not be detected by the probe. The frequencies of MN weregenerally higher in slides stained with DAPI than in those stainedwith MGG, especially in controls and clastogen-treated cultures.This finding probably reflects an underestimation with MGG ofsmall, light MN indistinguishable from the cytoplasmic background.
4To whom correspondence should be addressed 相似文献
35.
Leishmania major-Like Antigen for Specific and Sensitive Serodiagnosis of Human and Canine Visceral Leishmaniasis
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Rosngela Barbosa-de-Deus Marcos Luíz dos Mares-Guia Adriane Zacarias Nunes Ktia Morais Costa Roberto Gonalves Junqueira Wilson Mayrink Odair Genaro Carlos Alberto Pereira Tavares 《Clinical and Vaccine Immunology : CVI》2002,9(6):1361-1366
An antigen (LMS) prepared from Leishmania major-like promastigotes was used in an enzyme-linked immunosorbent assay (ELISA) for the diagnosis of human and dog visceral leishmaniasis. The results were compared with those from the indirect immunofluorescent antibody test (IFAT). A total of 1,822 canine sera were tested, including sera from dogs with visceral leishmaniasis, transmissible venereal tumors, ehrlichiosis, rickettsiosis, or Chagas' disease and sera from healthy dogs. The antigen was also tested with 227 samples of human sera, including sera from patients with visceral, cutaneous, or diffuse cutaneous leishmaniasis and from noninfected individuals, as well as sera from patients with Chagas' disease, toxoplasmosis, rickettsiosis, hepatitis B, schistosomiasis, ascaridiasis, malaria, rheumatoid factor, leprosy and rheumatoid factor, tuberculosis, or leprosy. All dogs and all human patients had a clinical and/or serological and/or parasitological diagnosis. For detecting antibodies in sera from dogs with leishmaniasis, the antigen showed a sensitivity of 98%, specificity of 95%, and concordance of 93% and when used for detecting antibodies in human sera presented a sensitivity of 92%, specificity of 100%, and concordance of 92%. Comparison between ELISA and IFAT demonstrated that ELISA using the LMS antigen yielded more reliable results than IFAT. The LMS antigen displayed no cross-reactivity with sera from patients or dogs that had any of the other diseases tested. 相似文献
36.
Replacement of Candida albicans with C. dubliniensis in human immunodeficiency virus-infected patients with oropharyngeal candidiasis treated with fluconazole
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![点击此处可从《Journal of clinical microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Martinez M López-Ribot JL Kirkpatrick WR Coco BJ Bachmann SP Patterson TF 《Journal of clinical microbiology》2002,40(9):3135-3139
Candida dubliniensis is an opportunistic yeast that has been increasingly implicated in oropharyngeal candidiasis (OPC) in human immunodeficiency virus (HIV)-infected patients but may be underreported due to its similarity with Candida albicans. Although most C. dubliniensis isolates are susceptible to fluconazole, the inducibility of azole resistance in vitro has been reported. Thus, the use of fluconazole prophylaxis in the treatment of these patients may have contributed to the increasing rates of isolation of C. dubliniensis. In this study, yeast strains were collected from the oral cavities of HIV-infected patients enrolled in a longitudinal study of OPC. Patients received fluconazole for the suppression or treatment of OPC, and isolates collected at both study entry and end of study were chosen for analysis. Samples were plated on CHROMagar Candida medium for initial isolation and further identified by Southern blot analysis with the species-specific probes Ca3 (for C. albicans) and Cd25 (for C. dubliniensis). Fluconazole MICs were determined by using NCCLS methods. At study entry, susceptible C. albicans isolates were recovered from oral samples in 42 patients who were followed longitudinally (1 to 36 months). C. albicans strains from 12 of these patients developed fluconazole resistance (fluconazole MIC, >/=64 micro g/ml). C. dubliniensis was not detected at end of study in any of these patients. Of the remaining 30 patients, eight (27%) demonstrated a replacement of C. albicans by C. dubliniensis when a comparison of isolates obtained at baseline and those from the last culture was done. For the 22 of these 30 patients in whom no switch in species was detected, the fluconazole MICs for initial and end-of-study C. albicans isolates ranged from 0.125 to 2.0 micro g/ml. For the eight patients in whom a switch to C. dubliniensis was detected, the fluconazole MICs for C. dubliniensis isolates at end of study ranged from 0.25 to 64 micro g/ml: the fluconazole MICs for isolates from six patients were 0.25 to 2.0 micro g/ml and those for the other two were 32 and 64 micro g/ml, respectively. In conclusion, a considerable number of patients initially infected with C. albicans strains that failed to develop fluconazole resistance demonstrated a switch to C. dubliniensis. C. dubliniensis in this setting may be underestimated due to lack of identification and may occur due to the impact of fluconazole on the ecology of oral yeast species. 相似文献
37.
Donangelo I Marcos HP Araújo PB Marcondes J Filho PN Gadelha M Chimelli L 《Endocrine pathology》2005,16(1):53-62
The retinoblastoma gene (RB1) is a tumor-suppressor gene in chromosomal region 13q14.2. Its role in the pathogenesis of pituitary tumors has not been
fully clarified. Some studies have shown that losses in this chromosomal region are related to aggressive tumor behavior,
although the retinoblastoma protein (pRB) is still expressed. Conversely, lack of expression of pRB was observed in one fourth
of GH-secreting pituitary adenomas (GH-tumors). In order to further study the expression of pRB in GH-tumors, we evaluated
this protein in 49 tumors from patients with acromegaly (20 noninvasive, 25 invasive, and 4 with no information) and 8 normal
pituitaries using immunohistochemistry (IHC). Nuclear staining for pRB ranged from 0 to 90% (median 40%) in the tumors and
from 40 to 80% (median 58%) in normal pituitaries. In 10 tumors (20% of total) the adenomatous cells were negative (5 cases)
or had very low labeling (5 cases) for pRB. Sixty three percent (31/49) of the tumors showed staining in 10–80% of the cells
and in 16% (8/49) of the cases >80% of the adenomatous cells were positive for pRB. The expression of pRB was not different
in invasive and noninvasive tumors. In conclusion, pRB is underexpressed in a subgroup of GH-tumors, and this may represent
an early event in the pathogenesis of this tumor subtype. 相似文献
38.
Traditionally, diagnosis and treatment have been seen as two distinct tasks. Consequently, most approaches to computer supported health care focus on one of the two-mostly on diagnosis or rather on the interpretation of measurements which is much better understood and formalised. However, in practice diagnosis and treatment overlap and influence each other in many ways. Combinations range from repeatedly going through the diagnosis-treatment loop over a period of time to permanent monitoring of the patients' health condition as it is done in intensive care units. In this article we describe how to model these combinations using the clinical protocol-representation language ASBRU. It implements treatment steps in a hierarchy of skeletal, time-oriented plans. Diagnosis can either be described in a declarative way in the conditions, under which treatment steps are taken or it can be modelled explicitly as plans of their own right. We demonstrate our approach using examples taken from the American Association of Paediatricians' guideline for the treatment of hyperbilirubinemia in the new-born. 相似文献
39.
M Rosario Sepúlveda Matias Hidalgo-Sánchez Daniel Marcos Ana M Mata 《Developmental dynamics》2007,236(5):1227-1236
The plasma membrane Ca(2+)-ATPase (PMCA) is highly expressed in the nervous system, but little information is available about its implication in neuronal development. We have analyzed the expression and localization of different isoforms of PMCA in membrane vesicles and sections of chick cerebellum from embryonic day 10 to hatching. We found that the relative amount of each PMCA isoform and their spatiotemporal distribution in the cerebellum are directly linked to precise cellular types during the cerebellar maturation, even in a non-neural tissue as choroid plexus. Purkinje cells contain the highest diversity of PMCA isoforms of the cerebellar cortex since the moment of its morphogenesis. From embryonic day 15, the PMCA2 was highly expressed in the whole Purkinje cell, while PMCAs 1 and 3 had a more restricted distribution in the soma and dendritic branches, and these distributions were evolving according with cell maturation. Other cellular types seem to contain a specific combination of isoforms, but with a well-defined distribution pattern at late moments of development. Thus, PMCAs 1 and 3 were located in the soma of molecular layer interneurons, and only the PMCA2 was observed in granule cells at hatching. Furthermore, PMCA isoforms are also expressed in cellular compartments characterized by a high amount of synapses, suggesting a key role of these proteins in synaptogenesis and in the maturation of neuronal electrophysiological properties. 相似文献
40.