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191.
L-Tyrosine-p-azobenzene-p-arsonate (RAT) is immunogenic and serves as a carrier for anti-hapten antibody responses in guinea pigs, rats, and mice. However, the murine anti-N-2,4-dinitrophenyl (DNP) plaque-forming cell (PFC) response to the bifunctional antigen 2,4-dinitrophenyl-6-amino-caproyl-L- tyrosine-p-azobenzene-p-arsonate (DNP-SAC-RAT; or BI-1) is extremely weak (2,000-4,000 PFC/spleen) and exclusively IgM in both primary and secondary responses. The 6-amino-caproyl group serves as a spacer in this antigen between the DNP haptenic and RAT carrier epitopes. In view of recent evidence indicating that different T helper cells synergize for optimal antibody responses, a trifunctional antigen, N-2,4- dinitrophenyl-6-amino-caproyl-L-tyrosine-p-azobenze-p-arsonate-(proline)9-L- tyrosine-p-azobenzene-p-arsonate (DNP-SAC-RAT-PRO(9)-RAT; or TRI), was prepared to investigate the effect of adding a second RAT epitope to BI-1. The nonaproline spacer between the two RAT epitopes in TRI is assumed to be a rigid rod of approximately 28 A. TRI induced about twice as many PFC as BI-1 in primary responses of A/J mice, and induced both IgM and IgG PFC in secondary responses. Furthermore, TRI induced IgG PFC responses in mice primed with p-azobenzene-p-arsonate-keyhole limpet hemocyanin, BI-1, or RAT, whereas boosting with BI-1 failed to induce IgG PFC, even in mice primed with TRI. These findings indicate that the minimum antigen structural requirements for inducing IgG PFC in mice are two carrier epitopes and one haptenic epitope. In addition, priming with a mono-epitope carrier (RAT) is sufficient preparation for IgG responses to a trifunctional immunogen. Because TRI differs from BI-1 by the (proline)(9) spacer as well as the additional RAT epitope, two other compounds, N-2,4-dinitrophenyl-6-amino- caproyl-(proline)(9)-L-tyrosine-p-azobenzene-p-arsonate (DNP-SAC-PRO(9)-RAT; or BI-2) and N-2,4-dinitrophenyl-6-amino-caproyl-(proline)(9)-L-tyrosine-p- azobenzene-arsonate (DNP-SAC-RAT-PRO(10); or BI-3), were prepared to evaluate the possible role of the spacer in the observed responses. BI-2, but not BI-3, induced IgG as well as IgM PFC in TRI-primed mice. However, BI-2 failed to induce IgG responses in RAT-primed mice, indicating that TRI and BI-2 were not equivalent immunogens. Because anti-prolyl antibodies had been found in guinea pigs immunized with N-2,4-dinitrophenyl-(proline)10-L-tyrosine-p- azobenzene-p-arsonate (DNP-PRO(10)-RAT), it seemed possible that priming with TRI might induce anti-prolyl antibodies, which, in turn, could cross-link BI-2 molecules into aggregates containing at least two carrier epitopes. To help resolve this question, mice were immunized with acetyl-(proline)10-L- tyrosine-p-azobenzene-p-arsonate and boosted with BI-2. IgG PFC responses were detected, suggesting that anti-prolyl antibodies were indeed responsible, because priming with RAT and boosting with BI-2 did not induce IgG formation. Accordingly, the observations that IgG responses in RAT-primed mice were induced only by TRI and not by any of the bifunctional antigens indicate that two carrier epitopes per antigen molecule are indeed required for IgG induction. They also provide indirect evidence for synergistic help in the switching of immunoglobulin isotypes. 相似文献
192.
Georgios K Efthimiadis Helen P Hassapopoulou Dimitrios D Tsikaderis Haralambos I Karvounis Georgios A Giannakoulas Georgios E Parharidis Georgios E Louridas 《Circulation journal》2006,70(8):1037-1042
BACKGROUND: The present study evaluated the prognostic significance of Doppler-demonstrated left ventricular (LV) restrictive filling pattern (RFP) in patients with thalassaemia major (TM), which carries an adverse cardiovascular prognosis. METHODS AND RESULTS: The study group comprised 45 asymptomatic transfusion-dependent patients with TM and normal LV systolic function. All patients were chelated with desferrioxamine. They were regularly evaluated by clinical and Doppler-echocardiographic studies throughout the 15-year follow-up period. The patients were categorized into 2 groups according to baseline data: those with LVRFP and those with LV non-RFP. The incidence of cardiac death in both groups was analyzed. The impact of chelation therapy on the ventricular filling pattern and survival was also examined. Nineteen patients (42.2%) had LVRFP and 26 (57.8%) had LV non-RFP. During follow-up 11 patients died from cardiac causes; 8 of them (72.8%) initially had LVRFP and 3 (27.2%) had LV non-RFP. LVRFP was significantly associated with mortality (p=0.018). Poor compliance with chelation therapy was significantly associated with LVRFP (p=0.007) and cardiac mortality (p=0.003). CONCLUSIONS: LVRFP is an important predictor of cardiac mortality in patients with TM. Poor compliance with chelation therapy was significantly associated with both a RFP (p=0.007) and cardiac mortality (p=0.003). 相似文献
193.
G K Efthimiadis G E Parharidis H I Karvounis K D Gemitzis I H Styliadis G E Louridas 《European journal of echocardiography》2002,3(2):143-148
AIMS: Left ventricular diastolic function in patients with hypertrophic cardiomyopathy has been adequately studied. In contrast there are few studies concerning right ventricular diastolic function in hypertrophic cardiomyopathy. We studied right ventricular diastolic function in patients with hypertrophic cardiomyopathy using Doppler echocardiography. METHODS AND RESULTS: We studied 20 patients with hypertrophic cardiomyopathy (mean age 43.6+/-13.8 years) and 20 healthy volunteers (control group, mean age 43+/-13.8 years). We calculated left ventricular and right ventricular diastolic indices using pulsed Doppler echocardiography. Hypertrophic cardiomyopathy patients compared with controls had significantly lower right ventricular-E/A ratio (1.01+/-0.40 vs 1.30+/-0.28, P<0.04), significantly prolonged right ventricular isovolumic relaxation time (170+/-72 vs 32+/-23 ms, P<0.001), and also significantly prolonged right ventricular deceleration time (160+/-58 vs 118+/-35 ms, P<0.01). There was also strong significant correlation between right ventricular deceleration time and left ventricular deceleration time (r=0.78), right ventricular-E/A ratio and left atrial filling fraction (r=-0.55) and between right atrial filling fraction and left atrial filling fraction (r=0.75). CONCLUSIONS: Right ventricular diastolic function in patients with hypertrophic cardiomyopathy is impaired, reflecting abnormal relaxation. Right ventricular diastolic indices correlate well with those of left ventricle. 相似文献
194.
B Hertel-Wulf JW Goodman CG Fathman GK Lewis 《The Journal of experimental medicine》1983,157(3):987-997
The antigen-induced proliferative response of lymph node cells (LNC) from mice sensitized to the monofunctional antigen L-tyrosine-p-azobenzenearsonate (ABA-Tyr) was used to monitor genetic control. All strains tested mounted significant responses, but those that were H-2(b) at both the I-A and I-E loci [B10., B6., B10.A(18R), A.BY, and C3H.SW] gave consistently weaker responses than other haplotypes. The F(1) progeny of matings between high and low responder phenotype parents (DBA/2 and B6, respectively) were high responders, establishing the dominance of the responder trait. Proliferative responses of LNC to ABA-Tyr were blocked by the appropriate anti-Ia monoclonal reagents. For example, B10.A(4R) LNCI (I-A(k), I-E(b)) were blocked by anti-I-A(k), whereas B10.A(3R) LNC (I-A(b), I-E(k)) were blocked by anti-I-E(k). Long-term cultures of T cell lines specifically reactive to ABA-Tyr were established from LNC of A/J mice immunized with ABA-Tyr and were cloned by limiting dilution. The proliferative responses to ABA-Tyr of 14 out of 15 clones tested were I-A restricted on the basis of activation by antigen-presenting cells from appropriate recombinant strains and the blocking activity of the monoclonal anti-Ia antibodies. The response of the other clone was I-E restricted. The fine antigen specificity of the clones was studied using structural analogs of the homologous antigen to induce proliferation. The clones could be divided into three types with respect to responsiveness to ABA-histidine (ABA-His). One group responded about equally well to ABA-His and ABA-Tyr. A second set responded less strongly to ABA-His than to ABA-Tyr, while the third showed no response above background to ABA- His. In all instances, the ABA-His-responding clones discriminated exquisitely between the 2-azo and 4-azo histidine isomers, responding only to the 4-azo compound. These T cell clones provide extremely useful tools for studies of T cell specificity, antigen recognition and lymphoid cell interaction systems. 相似文献
195.
Treatment of late bone marrow relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study 总被引:1,自引:4,他引:1
Children with acute lymphoblastic leukemia (ALL) who have completed 2.5 to 3 years of initial chemotherapy have an off-therapy relapse rate of approximately 20%. In an attempt to improve the survival of children with a late bone marrow (BM) relapse (ie, occurring greater than 6 months after cessation of primary therapy), the Pediatric Oncology Group designed a randomized study to compare the efficacy of doxorubicin/prednisone and cytarabine/teniposide in a multidrug retreatment chemotherapy program. Treatment consisted of remission reinduction with vincristine, prednisone, and doxorubicin, central nervous system prophylaxis with triple intrathecal chemotherapy, and continuation therapy (for 132 weeks) with alternating cycles of oral 6- mercaptopurine/methotrexate and intravenous vincristine/cyclophosphamide. Patients received intermittent courses of either prednisone/doxorubicin (regimen 1) or teniposide/cytarabine (regimen 2) during continuation therapy and a late intensification phase with either vincristine, prednisone, and doxorubicin (regimen 1) or teniposide and cytarabine (regimen 2). One hundred two of 105 evaluable patients (97%) achieved a second complete remission. Twenty- eight of 50 patients on regimen 1 have failed compared with 28 or 52 patients on regimen 2 (log-rank analysis, P = .68), indicating that this trial was inconclusive as to which treatment regimen was superior. The overall 4-year event-free survival for children with a late BM relapse was 37% +/- 6%. Age less than 10 years at initial diagnosis (P < or = .001), white blood cell count less than 5,000/microL at relapse (P = .036) and duration of first remission greater than 54 months (P = .039) were independently associated with a more favorable outcome. While the randomized trial was inconclusive, prolonged second complete remissions were secured in more than one-third of children with a late BM relapse of ALL. The prognostic factors identified may help select children with a late BM relapse who can be successfully retreated with chemotherapy alone. 相似文献
196.
Zegkos Thomas Ntelios Dimitris Parcharidou Despoina Katranas Sotiris Panagiotidis Theofilos Papanastasiou Christos A. Karagiannidis Efstratios Rouskas Pavlos Vassilikos Vassilis Karvounis Haralampos Efthimiadis Georgios K. 《The international journal of cardiovascular imaging》2021,37(9):2679-2690
The International Journal of Cardiovascular Imaging - Atrial fibrillation (AF) and heart failure (HF) represent clinical turning points, altering the natural history of HCM and influencing... 相似文献
197.
198.
Septal alcohol ablation in hypertrophic obstructive cardiomyopathy: improving cardiac function by generating a myocardial scar. 总被引:1,自引:0,他引:1
Georgios K Efthimiadis Nikolaos E Mezilis Georgios Giannakoulas Georgios E Parcharidis 《European heart journal》2007,28(10):1270-1; author reply 1271
We read with great interest the article by van Dockum et al.1on the improvement of systolic myocardial function of the leftventricular (LV) lateral (free) wall in patients with hypertrophic 相似文献
199.
G K Efthimiadis G E Parharidis K D Gemitzis I G Nouskas H I Karvounis I K Styliadis G E Louridas 《The Journal of heart valve disease》1999,8(3):261-269
BACKGROUND AND AIM OF THE STUDY: Left ventricular diastolic function (LVDF) in patients with aortic stenosis (AS) has been adequately studied, in contrast to right ventricular diastolic function (RVDF). In this study, RVDF in patients with AS was evaluated using pulsed-wave Doppler echocardiography. METHODS: The study population comprised 20 patients with isolated AS (mean age 53.7 +/- 6.5 years) and 20 healthy volunteers (control group, mean age 52.6 +/- 8.8 years). The diastolic indices of right ventricular (RV) function were calculated using transtricuspid and transpulmonary Doppler flow velocities. Statistical analysis was performed using Student's t-test. There was no statistically significant difference between patients and controls with regard to age, height, bodyweight, heart rate, systolic and diastolic blood pressures, end-diastolic and end-systolic left ventricular (LV) diameter, LV fractional shortening and RV end-diastolic diameter. RESULTS: RV diastolic indices in patients (versus controls) were as follows: E/A ratio of transtricuspid flow waves was significantly lower (0.88 +/- 0.20 versus 1.25 +/- 0.33, p < 0.001); deceleration time of E wave was significantly longer (184 +/- 3 versus 127 +/- 3 ms, p < 0.001); atrial filling fraction was significantly augmented (43.1 +/- 7.7 versus 33.6 +/- 7.6%, p < 0.001); and isovolumic relaxation time was significantly prolonged (116 +/- 73 versus 31 +/- 15 ms, p < 0.001). There was no statistically significant correlation between diastolic indices and interventricular septum thickness and LV mass index. CONCLUSIONS: RVDF in AS patients is impaired, reflecting abnormal relaxation. 相似文献
200.
P. Boura N. Lefkos G. Boudonas J. Kountouras E. Zacharioudaki AP. Efthimiadis G. Tsapas 《International journal of immunogenetics》1999,26(4):285-291
Immune-mediated mechanisms are involved in the pathogenesis of cardiomyopathies. In this study, we investigate which pattern of immune response (Th1 or Th2) lies behind these diseases by analysing the basic cytokines secreted from PHA-cultured T lymphocytes and determining what differences, if any, exist between dilated cardiomyopathy (DMC) and hypertrophic cardiomyopathy (HCM). Two groups of patients were studied: 10 patients with DCM and 10 patients with HCM. Age- and sex-matched healthy individuals were used as controls. PHA-cultured T lymphocytes in the presence or absence of different myocardial antigen (MA) concentrations were measured. Interleukine-2 (IL-2), Interleukine-6 (IL-6) and Interferon-γ (IFN-γ) levels were measured in culture supernatants by an ELISA method. At the same time, delayed-type hypereactivity (DTH) against the same antigenic preparation was measured by the leukocyte migration inhibitory index technique. Patients were subdivided into DTH-positive and DTH-negative and re-examined for IL-2 cytokine expression. IL-6 levels were found to increase both in the presence and in the absence of MA in the patient groups compared to the controls. IL-2 levels were decreased in both groups, in an antigen dose-related manner. Anergic patients showed a further reduction in IL-2 levels for both groups of patients. IFN-γ remained unaffected in the patient groups. Almost half of the patients exhibited anergy to the DTH reaction against MA. We conclude that, upon antigenic stimulation, the initially mounted immune response (increased IL-6) is somehow blocked/switched off in patients, resulting in an immunologic tolerance/unresponsiveness to MA (IL-2 decreased, IFN-γ unchanged). Finally, increased IL-6 could lead to a perpetuation of immunologic injury through the release of oxygen-free radicals with a cytotoxic effect on the myocardium. We hypothesize an antigen-related, defective macrophage-Th1 cell reaction, which accounts for the differences in the IL-2 profile between the DCM and HCM groups, that might cause local immune responses to lead to immunosuppression (immune tolerance effect), thus contributing to the pathogenesis of cardiomyopathies. 相似文献