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61.
Mixed lymphocyte reactivity and cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes in C57BL/10 congenic and B10.A recombinant mouse strains
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GM Shearer EC Lozner TG Rehn A Schmitt-Verhulst 《The Journal of experimental medicine》1975,141(4):930-934
Cell-mediated lympholysis (CML) to trinitrophenyl (TNP)-modified autologous splenic lymphocytes has been recently reported in the mouse (1). Both the sensitization and effector phases of this phenomenon were shown to be T-cell mediated. Effector cell specificity studies indicated that modification of the target cells is a necessary but insufficient requirement for cytolysis, and suggested that altered cell surface components controlled by genes mapping in the mouse major histocompatibility H-2 complex (MHC) are important in the specificity of the cytotoxic reaction (1). In allogeneic models the generation of cytotoxic effector cells has been shown to be preceded or accompanied by immunogen- induced proliferation of responding lymphocytes, i.e. a mixed lymphocyte reaction (MLR) (2-5), although the generation of effectors may not necessarily always be the consequence of extensive cell proliferation (5). If the induction of cytotoxic effector lymphocytes by modified syngeneic spleen cells is characteristic of sensitization with cellular alloantigens, one would expect to find that sensitization with TNP-modified autologous cells would also induce thymidine incorporation by the responding cells in the culture. The present report demonstrates that both stimulation of thymidine incorporation and generation of cytotoxic effector cells are part of the in vitro response to TNP-modified autologous lymphocytes. However, the MLR to TNP- modified autologous cells consistently appeared to be less pronounced when compared with an allogeneic MLR, whereas the cytotoxic activity of the effector cells generated by sensitization against TNP-modified autologous cells was frequently as high as that detected against H-2 alloantigens. These two components of reactivity to “modified self” are verified in several C57BL/10 congenic and B10.A recombinant mouse strains. 相似文献
62.
H-2-restricted cytotoxic effectors generated in vitro by the addition of trinitrophenyl-conjugated soluble proteins 总被引:3,自引:3,他引:3
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A Schmitt-Verhulst CB Pettinelli PA Henkart JK Lunney GM Shearer 《The Journal of experimental medicine》1978,147(2):352-368
Murine spleen cells from normal donors were cultured in vitro with trinitrobenzene sulfonate (TNBS)-conjugated soluble proteins, i.e., bovine gamma globulin (TNP-BGG) or bovine serum albumin (TNP-BSA). Addition of 100 μg of any of these TNP-proteins to the spleen cell cultures led to the generation of cytotoxic T-cell effectors which were H-2-restricted and TNP- specific. The lytic potential of such effectors was comparable to that generated by sensitization with TNBS-modified syngeneic cells, and was restricted to haplotypes shared at the K or K plus I-A, or the D regions of the H-2 complex. Greater effecter cell activity was generated by addition of TNP-BGG against TNBS-modified targets which shared K plus I-A than against modified targets which shared the D region with the responding cells, which suggests that the same immune response genes are involved when the response is generated by the addition of TNP-conjugated soluble proteins or of TNBS- modified cells. H-2-restricted, TNP-specific effecter cells were generated by culturing mouse spleen cells with syngeneic cells which had been preincubated with TNP- BGG or TNP-BSA for 1.5 h. The addition of unconjugated soluble proteins to the cultures did not result in cytotoxic effectors detectable on H-2-matched targets, whether the targets were prepared by modification with TNBS, or by incubation with either the unconjugated or TNP-conjugated proteins. Depletion of phagocytic cells in the tumor preparation by Sephadex G-10 column fractionation before incubation with TNP-BSA had no effect on their lysis by the relevant effector cells. Immunofluorescent staining of tumor target cells with anti-TNP antibodies indicated that TNP could be detected on the tumor cells within 10 rain of incubation with TNP-BSA. The cytotoxic response generated by addition of the TNP-proteins to spleen cell cultures was found to be T-cell dependent at the effector phase, as shown by the sensitivity of the lytic phase to absorbed RAMB and complement. Furthermore, the response did not appear to be attributable to antibody-dependent cellular cytotoxicity. Three mechanisms were considered which could account for the generation of H-2-restricted, TNP-specific, cytotoxic T-cell effectors by the addition of soluble TNP-proteins. These include covalent linkage of activated TNP groups from the soluble proteins to cell surface components, macrophage processing of the soluble conjugates and presentation to the responding lymphocytes in association with H-2-coded self structures, or hydrophobic interaction of the TNP-proteins to cell surfaces. Results obtained from sodium dodecyl sulfate gel patterns indicating that cell-bound TNP was still linked to BSA, and the observation that phagocytic-depleted cells could interact with the soluble TNP-proteins and function as H-2-restricted targets, appear not to favor the first two proposed mechanisms. 相似文献
63.
Familial hemiplegic migraine: a clinical comparison of families linked and unlinked to chromosome 19 总被引:5,自引:0,他引:5
GM Terwindt RA Ophoff J Haan RR Frants MD Ferrari for the DMGRG 《Cephalalgia : an international journal of headache》1996,16(3):153-155
We compared the clinical characteristics of 50 patients from three unrelated families with familial hemiplegic migraine (FHM) linked to chromosome 19, with those of 20 patients from two families with FHM not linked to chromosome 19. We found no significant differences for age at onset, frequency and duration of attacks, duration of the paresis, and occurrence of basilar migraine symptoms. In the linked families, significantly more patients reported unconsciousness during attacks (39%, vs 15%; p<0.05) and provocation of attacks by mild head trauma (70% vs 40%; p< 0.05). In one linked family patients also displayed chronic progressive cerebellar ataxia, whereas in one unlinked family benign infantile convulsions occurred in addition to FHM. Interestingly, so far an association with cerebellar ataxia was only described in chromosome 19-linked families. FHM linked to chromosome 19 and FHM unlinked to chromosome 19 do not differ with respect to clinical features. 相似文献
64.
Specificity of cytotoxic effector cells directed against trinitrobenzene sulfonate-modified syngeneic cells. Failure to recognize cell surface- bound trinitrophenyl dextran
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PA Henkart A Schmitt-Verhulst GM Shearer 《The Journal of experimental medicine》1977,146(4):1068-1078
Mouse splenic lymphocytes and lymphoid tumor cells were modified with the trinitrophenyl (TNP) group either by treatment with trinitrobenzene sulfonate (TNBS) (which covalently modifies cell surface proteins) or with TNP stearoyl dextran (TSD) (which binds to the cell by noncovalent forces). These cell preparations were compared for their ability to: (a) sensitive syngeneic splenic lymphocytes leading to the generation of cytotoxic effector cells; (b) serve as lysable targets in a 4-h(51)Cr- release assay for effector cells generated in (a); and (c) act as blocking cells in the lysis of TNBS-medified targets lysed by TNP self effector cells generated in (a). In none of these three experimental systems did TSD-medified syngeneic spleen or H-2-matched tumor cells act either as a sensitizing immunogen or as a target antigen, despite the demonstration that quantitatively equivalent mounts of TNP were exposed on the cell surface in the TNBS- and TSD-modified cells. In contrast, TNBS-modified spleen cells sensitized syngeneic lymphocytes to generate effectors against TNBS-modified syageneic targets. Furthermore, TNBS- modified, H-2-matched cells served as specific lysable targets and as inhibiting cells for such effectors. These results indicate that the manner in which TNP is associated with the cell surface is important in the immunogenicity and antigenicity of hapten-modified syngeneic stimulating cells in generating H-2-associated cell-mediated lympholysis (CML) reactions. These findings raise the possibility that a covalent or at least a stable linkage with cell surface proteins (possibly H-2- controlled products) is important for immunological function. Furthermore, these observations do not favor the dual receptor model for H-2-restricted syngeneic CML if it is assumed in such a model that one receptor is specific for the TNP moiety and the second for unmodified self major histocompatibility products. 相似文献
65.
The present criteria for confirmation of human T-lymphotrophic virus types I and II (HTLV-I/II) infection in blood donors are based on seroreactivity to p24 (gag) and gp46 and/or gp61 (env) on Western blot (WB) and radioimmunoprecipitation assays (WB/RIPA). Any single band and other combinations are classified as indeterminate. This case report documents infection in a donor with a repeatedly indeterminate pattern. The blood donor was anti-HTLV-I/II positive on enzyme-linked immunoassay, and two sera taken 5 years apart were WB/RIPA-indeterminate (p19 and gp68 only). His donations in the interval were associated with transmission of HTLV-I to four of the six recipients available for study. Other recipients of blood from donors whose WB/RIPA results were indeterminate by present criteria should be examined to determine if additional patterns are at least occasionally associated with transmission. The likelihood that such donors are infected is important to those who are counseling them and making decisions concerning recipients of their bloody. 相似文献
66.
GM Repetto ML Guzmán A Puga JF Calderón CP Astete M Aracena M Arriaza T Aravena P Sanz 《Clinical genetics》2009,76(5):465-470
Patients with chromosome 22q11 deletion syndrome exhibit significant phenotypic variability. Epidemiologic data suggest a higher incidence in Hispanics, but limited clinical information is available from Latin-American patients. We describe the clinical features of Chilean patients with 22q11 deletion syndrome and compare their findings with those reported in large European, Japanese and US series. Data were obtained from 208 patients from five medical centers. Mean age at diagnosis was 5.2 years, with a median of 2.3 years. Congenital heart defects were present in 59.6%, lower than other large series that averaged 75.8%. Palate abnormalities were present in 79%, higher than previous reports averaging 56%. Patients with congenital heart disease were diagnosed earlier (median 0.3 years of age) than those without heart defects (median 5.6 years) and had greater mortality attributable to the syndrome (9.8% vs 2.4%, respectively). The differences in frequencies of major anomalies may be due to growing awareness of more subtle manifestations of the syndrome, differences in clinical ascertainment or the presence of modifier factors. These observations provide additional data useful for patient counseling and for the proposal of health care guidelines. 相似文献
67.
S Pierno GM Camerino V Cippone J-F Rolland J-F Desaphy A De Luca A Liantonio G Bianco JD Kunic AL George Jr D Conte Camerino 《British journal of pharmacology》2009,156(8):1206-1215
Background and purpose:
Statins and fibrates can produce mild to life-threatening skeletal muscle damage. Resting chloride channel conductance (gCl), carried by the ClC-1 channel, is reduced in muscles of rats chronically treated with fluvastatin, atorvastatin or fenofibrate, along with increased resting cytosolic calcium in statin-treated rats. A high gCl, controlled by the Ca2+-dependent protein kinase C (PKC), maintains sarcolemma electrical stability and its reduction alters muscle function. Here, we investigated how statins and fenofibrate impaired gCl.Experimental approach:
In rats treated with fluvastatin, atorvastatin or fenofibrate, we examined the involvement of PKC in gCl reduction by the two intracellular microelectrodes technique and ClC-1 mRNA level by quantitative real time-polymerase chain reaction. Direct drug effects were tested by patch clamp analysis on human ClC-1 channels expressed in human embryonic kidney (HEK) 293 cells.Key results:
Chelerythrine, a PKC inhibitor, applied in vitro on muscle dissected from atorvastatin-treated rats fully restored gCl, suggesting the involvement of this enzyme in statin action. Chelerythrine partially restored gCl in muscles from fluvastatin-treated rats but not in those from fenofibrate-treated rats, implying additional mechanisms for gCl impairment. Accordingly, a decrease of ClC-1 channel mRNA was found in both fluvastatin-and fenofibrate-treated rat muscles. Fenofibric acid, the in vivo metabolite of fenofibrate, but not fluvastatin, rapidly reduced chloride currents in HEK 293 cells.Conclusions and implications:
Our data suggest multiple mechanisms underlie the effect of statins and fenofibrate on ClC-1 channel conductance. While statins promote Ca2+-mediated PKC activation, fenofibrate directly inhibits ClC-1 channels and both fluvastatin and fenofibrate impair expression of mRNA for ClC-1. 相似文献68.
Pablo F. Belaunzarán-Zamudio Miguel L. García-León Rosa María Wong-Chew Angelina Villasís-Keever Jennifer Cuellar-Rodríguez Juan L. Mosqueda-Gómez Teresa Muñoz-Trejo Kenia Escobedo José I. Santos Guillermo M. Ruiz-Palacios Juan G. Sierra-Madero 《Vaccine》2009
Objective
: The objective of the study was to evaluate the immune response to measles vaccine of HIV-infected adults in comparison to HIV non-infected adults.Design
We conducted a cross-sectional study to identify adults lacking measles antibodies. 26 HIV-infected patients and 22 controls found to be measles seronegative in the cross-sectional study, received the MMR vaccine. We prospectively followed patients and measured measles antibodies, and cellular proliferative responses against measles antigens. We registered all adverse events at baseline, 3 and 12 months after vaccination.Methods
We determined measles antibodies by ELISA and cellular proliferative response in PBMC's at baseline, and repeated measurements at 3 and 12 months after vaccination.Results
The humoral immune response to the vaccine between HIV-infected adults and the HIV-uninfected group was not statistically different at 3 months (81% vs. 86% respectively). One year after vaccination, a higher proportion of HIV-infected adults had lost measles antibodies in contrast to controls. The cellular response was not statistically different between the groups at baseline, 3 and 12 months after immunization despite the waning of antibodies at 12 months. No severe adverse events were observed. Most patients were receiving HAART and had a mean CD4+ cell count of 496 cells/mL.Conclusions
The initial humoral immune response to measles vaccine was not different between HIV-infected adults and HIV-uninfected adults. However, HIV-infected adults have a rapid decline of measles antibodies despite their high CD4+ cell count and sustained cellular proliferative response. 相似文献69.
Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases 总被引:1,自引:1,他引:0
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Huijts PE Vreeswijk MP Kroeze-Jansema KH Jacobi CE Seynaeve C Krol-Warmerdam EM Wijers-Koster PM Blom JC Pooley KA Klijn JG Tollenaar RA Devilee P van Asperen CJ 《Breast cancer research : BCR》2007,9(6):R78-9
Introduction
Seven SNPs in five genomic loci were recently found to confer a mildly increased risk of breast cancer.Methods
We have investigated the correlations between disease characteristics and the patient genotypes of these SNPs in an unselected prospective cohort of 1,267 consecutive patients with primary breast cancer.Results
Heterozygote carriers and minor allele homozygote carriers for SNP rs889312 in the MAP3K1 gene were less likely to be lymph node positive at breast cancer diagnosis (P = 0.044) relative to major allele homozygote carriers. Heterozygote carriers and minor allele homozygote carriers for SNP rs3803662 near the TNCR9 gene were more likely to be diagnosed before the age of 60 years (P = 0.025) relative to major allele homozygote carriers. We also noted a correlation between the number of minor alleles of rs2981582 in FGFR2 and the average number of first-degree and second-degree relatives with breast cancer and/or ovarian cancer (P = 0.05). All other disease characteristics, including tumour size and grade, and oestrogen or progesterone receptor status, were not significantly associated with any of these variants.Conclusion
Some recently discovered genomic variants associated with a mildly increased risk of breast cancer are also associated with breast cancer characteristics or family history of breast cancer and ovarian cancer. These findings provide interesting new clues for further research on these low-risk susceptibility alleles. 相似文献70.
Identification of women with an increased risk of developing radiation-induced breast cancer: a case only study
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Annegien Broeks Linde M Braaf Angelina Huseinovic Anke Nooijen Jos Urbanus Frans BL Hogervorst Marjanka K Schmidt Jan GM Klijn Nicola S Russell Flora E Van Leeuwen Laura J Van 't Veer 《Breast cancer research : BCR》2007,9(2):1-9