Epstein-Barr virus latent membrane protein-1 oncogene deletions: correlations with malignancy in Epstein-Barr virus--associated lymphoproliferative disorders and malignant lymphomas.

LMP-1, an Epstein-Barr viral (EBV) latency protein, is considered a viral oncogene because of its ability to transform rodent fibroblasts in vivo and render them tumorigenic in nude mice. In human B cells, EBV LMP-1 induces DNA synthesis and abrogates apoptosis. LMP-1 is expressed in EBV-transformed lymphoblastoid cell lines, nasopharyngeal carcinoma (NPC), a subset of Hodgkin's disease (HD), and in EBV-associated lymphoproliferative disorders (EBV-LPDs). Recently, focused deletions near the 3' end of the LMP-1 gene (del-LMP-1, amino acids 346-355), in a region functionally related to the half-life to the LMP-1 protein, have been reported frequently in human immunodeficiency virus (HIV)-associated HD (100%) and EBV+ Malaysian and Danish peripheral T-cell lymphomas (100%, 61% respectively), but less frequently in cases of HD not associated with HIV (28%, 33%) and infectious mononucleosis (33%). To further investigate the potential relationship of del-LMP-1 to EBV-LPDs associated with immunosuppression or immunodeficiency, we studied 39 EBV-associated lymphoproliferations (10 benign, 29 malignant) from four distinct clinical settings: posttransplant (4 malignant, 1 reactive); HIV+ (18 malignant, 2 reactive); nonimmunodeficiency malignant lymphoma (ML) (7 cases); and sporadic EBV infection with lymphoid hyperplasia (7 cases). The presence of EBV within lymphoid cells was confirmed by EBV EBER1 RNA in situ hybridization or by polymerase chain reaction (PCR) analysis. EBV strain type and LMP-1 deletion status were determined by PCR. EBV strain types segregated into two distinct distributions: HIV+ (9 A; 11 B) and non-HIV (19 A, 0 B), consistent with previous reports. Overall, del-LMP-1 were found in 1 of 5 (20%) Burkitt lymphomas (BL); 17 of 24 (71%) aggressive non-Hodgkin's lymphoma (agg-NHL), and 2 of 10 (20%) reactive lymphoid proliferations. Of the agg-NHLs, del-LMP-1 were present in 4 of 4 PT-ML (100%); 10 of 15 HIV+ ML (67%); and 3 of 5 nonimmunodeficiency malignant lymphoma (ML, 60%). A total of 2 of 7 (28%) sporadic EBV-associated lymphoid hyperplasias contained a del-LMP-1. All del-LMP-1 were identical by DNA sequence analysis. No correlation was identified between the presence of del-LMP-1 and the EBV strain type observed. The high incidence of del-LMP-1 observed in agg-NHLs (71%), in contrast to the relatively low incidence observed in reactive lymphoid proliferations (28%), suggests that the deleted form may be preferentially selected in lymphomatous processes. All posttransplant agg-NHLs contained a del-LMP-1, and a similar frequency of del-LMP-1 was observed in both HIV-associated ML (66%) and nonimmunodeficiency ML (60%), suggesting that impairment of immune function alone is not a requirement for the expansion of malignant cells infected by EBV stains containing the deleted LMP-1 gene.

Primary cutaneous Hodgkin's disease with evolution to systemic disease. Association with the Epstein-Barr virus.

Hodgkin's disease rarely involves the skin and when it does is an indication of advanced stage disease. Primary cutaneous Hodgkin's disease is exceedingly rare, and only a few cases are reported. We describe a patient who developed multiple cutaneous lesions of Hodgkin's disease 2 years before manifesting nodal disease of mixed cellularity subtype. Reed-Sternberg cells in the skin as well as lymph nodes and bone marrow were positive for Epstein-Barr viral transcripts and expressed viral latent membrane protein. Epstein-Barr virus has not previously been demonstrated in primary cutaneous Hodgkin's disease, and its presence in lesions in all sites in this case supports a diagnosis of primary cutaneous disease with subsequent evolution into systemic disease.

Influence of lung injury on pulmonary wedge-left atrial pressure correlation during positive end-expiratory pressure ventilation.

The correlation between pulmonary artery wedge pressure (Pw) and left atrial pressure (Pla) requires a continuous fluid column between the catheter tip and the left atrium. We hypothesized that lung injury may protect the fluid column from the collapsing effects of increased airway pressure. Correlation between Pw and Pla would then depend on catheter tip location in injured versus normal lung regions. In 7 anesthetized dogs with unilateral acid pneumonitis, we compared Pla and simultaneous Pw measurements from pulmonary artery catheters located in injured and normal lungs at different levels of positive end-expiratory pressure (PEEP). Studies were repeated in 10 dogs with normal lungs and 5 dogs with bilateral acid pneumonitis. In supine dogs with unilateral lung injury, Pw from the injured lung more accurately reflected Pla than did Pw obtained from the normal lung at PEEP levels of 7 mmHg or higher, in contrast to data from dogs with normal lungs or equally injured lungs. Discrepancies between Pw and Pla at PEEP levels of 7 and 11 mmHg from the normal lung were corrected when that lung was placed in the dependent position to increase venous pressure at the catheter tip. A good Pw-Pla correlation was not guaranteed by catheter tip location below the level of the left atrium during PEEP ventilation. We conclude that the continuity of the fluid column was protected by lung injury. Although Pw-Pla differences from the normal lung were modest at the levels of PEEP that are usually optimal for gas exchange in uneven lung injury, it is recommended that the injured lung should not be avoided during insertion of the balloon-tipped catheter.