Participation of CD45, NKR-P1A and ANK61 antigen in rat hepatic NK cell (pit cell)mediated target cell cytotoxicity

AIM Several triggering receptors have been described to be involved in natural killer (NK) cellmediated target cytotoxicity. In these studies, NK cells derived from blood or spleen were used. Pit cells are liver-specific NK cells that possess a higher level of natural cytotoxicity and a different morphology when compared to blood NK cells. The aim of this study was to characterize the role of the NK-triggering molecules NKR-P1A, ANK61 antigen, and CD45 in pit cell-mediated killing of target cells. METHODS 51 Cr-release and DNA fragmentation were used to quantify target cell lysis and apoptosis, respectively. RESULTS Flow cytometric analysis showed that pit cells expressed CD45, NKR-P1A, and ANK61 antigen. Treatment of pit cells with monoclonal antibody ( mAb ) to CD45 ( ANK74 ) not only inhibited CC531s or YAC-1 target lysis but also apoptosis induced by pit cells. The mAbs to NKRP1A (3.2.3) and ANK61 antigen (ANK61) had no effect on pit cell-mediated CC531s or YAC-1 target cytolysis or apoptosis, while they did increase the Fcγ receptor positive (FcγR+) P815 cytolysis and apoptosis. This enhanced cytotoxicity could he inhibited by 3,4-dichloroisocoumarin, an inhibitor of granzymes. CONCLUSION These results indicate that CD45 participates in pit cell-mediated CC531s and YAC-1 target cytolysis and apoptosis. NKR-P1A and ANK61 antigen on pit cells function as activation structures against FcγR+ P815 cells, which was mediated by the perforin/granzyme pathway.     

Prospective trial of electroanatomically guided, irrigated catheter ablation of atrial tachycardia in patients with congenital heart disease

BACKGROUND: Ablation success rates reported for atrial tachycardia (AT) patients with congenital heart disease (CHD) is lower than the rates reported for other varieties of supraventricular tachycardia. Retrospective studies suggest these rates might be increased by the use of irrigated radiofrequency (RF) ablation. OBJECTIVES: The purpose of this study was to determine whether irrigated RF ablation increases ablation success rates in patients with CHD and AT. METHODS: Patients were studied in a prospective, randomized, nonblinded manner. The operator was limited to use of randomized therapy (standard or irrigated ablation) for the first 6 minutes of RF application to each targeted arrhythmia. Lesion characteristics were recorded, and acute ablation success was ascertained. Structured clinical follow-up was performed over a 6-month period. RESULTS: Forty-seven ATs were targeted in 26 patients; 72% of these ATs were ablated. Within the 6-minute randomization period, no difference in success rates of standard and irrigated catheters was noted. However, crossover from standard to irrigated ablation more likely was successful than vice versa (irrigated: 8 successes/8 attempts vs standard: 1 success/4 attempts, P = .018), and overall success was greater using irrigated catheters (66% vs 33%, P = .019). Mean delivered power was slightly higher in irrigated lesions (32.5 W vs 30.2 W, P = .025), and mean temperature was much lower (33.5 degrees C vs 59.3 degrees C, P < .001). A composite AT intensity score was significantly reduced compared with preablation values at 6-month follow-up of all patients. CONCLUSIONS: Ablation of ATs in patients with CHD results in symptomatic improvement over short-term follow-up. Irrigated ablation may result in higher acute success rates in these patients.     

Preventing Arrhythmic Death in Patients With Tetralogy of Fallot: JACC Review Topic of the Week

Patients with tetralogy of Fallot are at risk for ventricular arrhythmias and sudden cardiac death. These abnormalities are associated with pulmonary regurgitation, right ventricular enlargement, and a substrate of discrete, slowly-conducting isthmuses. Although these arrhythmic events are rare, their prediction is challenging. This review will address contemporary risk assessment and prevention strategies. Numerous variables have been proposed to predict who would benefit from an implantable cardioverter-defibrillator. Current risk stratification models combine independently associated factors into risk scores. Cardiac magnetic resonance imaging, QRS fragmentation assessment, and electrophysiology testing in selected patients may refine some of these models. Interaction between right and left ventricular function is emerging as a critical factor in our understanding of disease progression and risk assessment. Multicenter studies evaluating risk factors and risk mitigating strategies such as pulmonary valve replacement, ablative strategies, and use of implantable cardiac-defibrillators are needed moving forward.     

A method for simultaneous study of the karyotype, morphology, and immunologic phenotype of mitotic cells in hematologic malignancies

A major problem in the cytogenetic analysis of hematologic neoplasms has been an inability to identify the cell from which the chromosomes were obtained. We describe a procedure that allows simultaneous analysis of karyotype and cell cytology in mitotic cells. The method differs from conventional cytogenetic analysis in that after mild hypotonic treatment, the cells are cytocentrifuged onto glass slides. In mitotic cells, this procedure often results in adequate spread of the chromosomes within the intact cell membrane. The cytoplasmic structure also remains intact, so that cytologic preparations are of good quality. Morphologic and immunologic identification of mitotic cells can be done using routine hematologic stains, such as Giemsa or Sudan black B, and various antisera using immunofluorescence techniques. The chromosomes can be simultaneously analyzed either without banding on slides stained with Giemsa or with Q-banding on slides stained with immunofluorescence techniques. Identification of numerical and structural karyotype aberrations thus is possible in morphologically identified cells.     

Acute renal rejection versus acute tubular necrosis in a canine model: MR evaluation

Findings of magnetic resonance (MR) imaging in acute renal rejection and acute tubular necrosis (ATN) were studied in dogs. On T1-weighted images, corticomedullary differentiation was absent in kidneys undergoing acute rejection. The loss of corticomedullary differentiation in these kidneys was secondary to a decrease in the relative signal intensity of the cortex, indicating prolongation of the T1 relaxation time of the cortex. In contrast, corticomedullary differentiation was preserved on T1-weighted images of autotransplanted kidneys and kidneys with ATN. MR imaging findings correlated with changes in water content in these three groups of kidneys. Kidneys undergoing acute rejection showed a marked increase in water content compared with kidneys in the other two groups. No change in fat content was found in any group.