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Background: Hemorrhagic transformation (HT) following acute ischemic stroke is a major problem, especially for the indication of reperfusion therapy including intravenous administration of recombinant tissue plasminogen activator (IV rt-PA). The specific predictive factors of HT have not yet been established. The present study evaluated the findings of computed tomography perfusion (CTP) images as predictors of subsequent HT to identify patients with low HT risk for reperfusion therapy such as IV rt-PA., Methods: We retrospectively reviewed 68 consecutive stroke patients (41 males; mean age 72.9 years) with steno-occlusive lesions in the major trunk, including 10 patients who underwent IV rt-PA. Each HT was detected on a follow-up T2*-weighted magnetic resonance image until 2 weeks after stroke onset and categorized into four groups [hemorrhagic infarction (HI) type 1 and 2, and parenchymal hematoma (PH) type 1 and 2] according to the European Cooperative Acute Stroke Study (ECASS) classification. We assessed clinical features and radiological findings between the HT and non-HT groups or the PH2 and non-PH2 groups. The efficacy of initial time to peak (TTP) mapping of CTP for predicting HT or PH2 was evaluated., Results: Thirty-four patients (50%) developed subsequent HT: 18 (52.9%) had HI and 16 (47.1%) had PH, including 9 PH2 patients (13.2%). IV rt-PA was not significantly associated with HT or PH2 occurrence. Forty of the 68 patients (59%) revealed defect areas on the initial TTP mapping (TTP map-defect), and 34 of these 40 patients (85%) developed secondary HT and 9 patients (22.5%) developed PH2. Initial 'TTP map-defect' was significantly associated with the occurrence of HT (p < 0.0001) and PH2 (p = 0.0070). Thirty of the 34 patients (88.2%) in the HT group experienced delayed recanalization of the occluded vessels, in contrast to only 8 of the 34 patients (23.6%) in the non-HT group. All patients of the PH2 group showed recanalization (p = 0.0042). In 40 'TTP map-defect'-positive patients, delayed recanalization was associated with the occurrence of HT (p < 0.0001) and PH2 (p = 0.0491). All 28 patients without 'TTP map-defect' did not develop HT, including 8 patients (28.6%) with delayed recanalization., Conclusions: Initial 'TTP map-defect' of CTP could accurately predict HT risk including PH2 risk and identify low-risk patients even in the delayed period.

Leukemic lymphocytes with B-cell markers were obtained from the peripheral blood of 4 patients with chronic lymphocytic leukemia (CLL) or acute lymphocytic leukemia (ALL); a significant number of T cells was not involved. The lymphocytes were inoculated with the transforming B95-8 Epstein-Barr virus (EBV). Synthesis of EBV-determined nuclear antigen (EBNA) occurred in three CLL preparations: 15.1--25.4% of cells expressed maximum EBNA 24--48 h after viral exposure. A characteristic immunofluorescence pattern similar to a coarsely clumped chromatin structure was observed. In contrast to EBV infection of normal lymphocytes, EBNA synthesis in CLL cells (morphologically similar to normal lymphocytes) was not followed by either blastogenesis or DNA synthesis. EBNA-positive cells, which usually degenerate within 1--2 weeks, could be maintained for more than 30 days on feeder human embryo fibroblasts pretreated with mitomycin C. DNA synthesis and mitosis occurred, but unlimited cell growth did not. 41.9% of ALL cells were EBNA-positive at 36 h prior to DNA synthesis, and they subsequently grew rapidly for up to 9 days. The cell proliferation, however, was temporary, and death resulted in about 2 weeks. No significant synthesis of EBV-related early antigens and viral capsid antigen was noted in any of the infected cultures throughout the incubation period. These results indicate that certain intracellular restrictions may have exceeded the potent transforming capacity of EBV in these target leukemic cells.

A B-cell population of human cord blood lymphocytes was exposed to the B95-8 strain of Epstein-Barr virus (EBV), and simultaneous observations of immunofluorescence, cellular morphology and autoradiography were carried out in each individual cell. It was evident that EBV-determined nuclear antigen (EBNA) synthesis occurred prior to blastogenic response and DNA synthesis. EBNA-positive cells could be observed as early as 12 h after infection and reached a maximum of 17% at 24 h, followed by a plateau for a subsequent 12 h. The positive cells were seen exclusively as morphologically normal lymphocytes until 18 h; at 24 h, blastogenesis became evident, without cell division. DNA synthesis was detected at 36 h in EBNA-positive blast cells, after which these cells increased rapidly. EBNA synthesis was similarly evident in the presence of cytosine arabinoside, but was significantly inhibited by a short-term exposure to cycloheximide immediately after infection. These findings suggest that the early events in EBV-induced transformation of human lymphocytes occur sequentially from EBNA synthesis, to blastogenesis, to DNA synthesis and that the crucial step of such transformation is probably involved in protein synthesis occurring in the very early stage of EBV infection.

We examined Epstein-Barr virus (EBV) in saliva samples and peripheral blood mononuclear cells (PBMC) from 9 patients with acute infectious mononucleosis (IM) and 4 patients with chronic active EBV infection (CEBV). All saliva samples from patients with acute IM were positive for EBV by both Southern blot hybridization assay and the cord transformation assay. In contrast, EBV DNA could not be detected in saliva samples from patients with CEBV. Only one of the saliva samples from 4 patients with CEBV could transform cord blood lymphocytes with extreme difficulty. No saliva samples from patients with CEBV were capable of inducing early antigens in Raji cells. On the other hand, EBV DNA was detected in PBMC from 3 of the 4 patients with CEBV but not in those from patients with acute IM by Southern blot hybridization. Spontaneous lymphoblastoid cell lines could be easily established from PBMC of patients with acute IM but not from PBMC of patients with CEBV, despite several attempts. Viral capsid antigen and early antigens were not observed in cultured cells from patients with CEBV. These results suggest that the main site of EBV replication in CEBV might not be oropharyngeal epithelial cells.

On the basis of the sequential early events induced by Epstein-Barr virus (EBV), the infectivity of human lymphocytes to EBV was quantified as a plateau value of the maximum nuclear antigen (EBNA) synthesis preceding cellular DNA synthesis. The frequency of EBV-infectible cells was an average of 7.6% of unfractionated umbilical cord lymphocytes and was 4.9% in the counterparts from human adults. In the B-cell-enriched populations, the average plateau values were 29.2% in umbilical cord and 15.5% in adult samples. This method is simple and applicable for quantitative assay of the sensitivity to EBV infection of a given lymphocyte preparation.

Nuclear antigen (EBNA) inducibility by Epstein-Barr virus (EBV) was assessed in relation to the presence of complement (C3) receptors and surface immunoglobulins (SIg) on leukemic lymphocytes. When erythrocyte-antibody-complement complex(EAC)-positive, SIg-negative B cells were exposed to EBV, EBNA synthesis occurred with a high frequency. In contrast, no significant EBNA induction was evident in SIg-positive, EAC-negative B cells. Cells possessing both markers were EBV-infectable, in proportion to the frequency of EAC-rosette formation. These data seem to indicate that EBV susceptibility of human B cells is closely related to the presence of C3 receptors but not SIg. Leukemic T cells and myelogenous leukemia cells were not EBV-susceptible, although some cells were significantly positive for C3 receptors.

Peripheral blood lymphocytes from 7 patients with ataxia telangiectasia were transformed by Epstein-Barr virus, and lymphoblastoid cell lines (LCL) were established. Immunoglobulin levels in the supernatants of the LCL were measured in order to analyze immunological abnormalities, especially the low levels of serum IgA in these patients. We found that the geometric means of IgA production in the supernatants of the LCL from the 7 patients were significantly lower than those from 9 healthy controls (5.0 vs. 834 ng/ml, p less than 0.001). These results indicate that the low levels of serum IgA in ataxia telangiectasia are attributable at least in part to an intrinsic abnormality of B cells.

When human epithelial FL cells were fused with lymphoid cells harboring Epstein-Barr virus (EBV) genome, EBV-determined nuclear antigen (EBNA) immunofluorescence became evident in high frequency in FL nuclei of heterokaryons several days after fusion. The implications of the findings are discussed in relation to the presence of EBV genome in nasopharyngeal carcinoma cells.