Craig E. Metroka

Non-Hodgkin's lymphoma in 90 homosexual men: relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome

We describe the histologic and clinical features of non-Hodgkins lymphoma diagnosed between January 1980 and December 1983 in 90 homosexual men from San Francisco, Los Angeles, Houston, and New York. The median age was 37 years, with an age distribution identical to that for cases of AIDS reported to the Centers for Disease Control. Sixty-two per cent of the patients had high-grade (aggressive) subtypes of lymphoma, 29 per cent had subtypes of intermediate grade, and 7 per cent had low-grade subtypes. Histologic subtypes and malignant cell phenotypes were consistent with a B-cell origin. All but two men had extranodal lymphoma: central-nervous-system, bone-marrow, bowel, and mucocutaneous sites were most commonly involved. Thirty-five of 66 evaluable men (53 per cent) had complete responses to combination chemotherapy or radiotherapy or both, and thus far, 19 (54 per cent) of them have had a relapse. Mortality and morbidity were closely related to prodromal manifestations; death or illness have occurred in 19 (91 per cent) of the 21 men who presented with AIDS, in 26 (79 per cent) of the 33 who presented with generalized lymphadenopathy, and in 5 (42 per cent) of the 12 who had no prodromal manifestations. Mortality rates analyzed according to histologic grade were higher than currently reported rates in other patient populations. Kaposis sarcoma or severe opportunistic infections characteristic of AIDS developed in 14 of 33 men (42 per cent) who presented with generalized lymphadenopathy and in 3 of 12 (33 per cent) without prodromal manifestations. We conclude that non-Hodgkins lymphoma in members of an AIDS risk group is a serious manifestation of AIDS and the AIDS-related complex.

Kaposi's Sarcoma-Associated Herpesvirus Open Reading Frame 50/Rta Protein Activates the Entire Viral Lytic Cycle in the HH-B2 Primary Effusion Lymphoma Cell Line

ABSTRACT Rta, the gene product of Kaposis sarcoma-associated herpesvirus (KSHV) encoded mainly in open reading frame 50 (ORF50), is capable of activating expression of viral lytic cycle genes. What was not demonstrated in previous studies was whether KSHV Rta was competent to initiate the entire viral lytic life cycle including lytic viral DNA replication, late-gene expression with appropriate kinetics, and virus release. In HH-B2, a newly established primary effusion lymphoma (PEL) cell line, KSHV ORF50 behaved as an immediate-early gene and autostimulated its own expression. Expression of late genes, ORF65, and K8.1 induced by KSHV Rta was eliminated by phosphonoacetic acid, an inhibitor of viral DNA polymerase. Transfection of KSHV Rta increased the production of encapsidated DNase-resistant viral DNA from HH-B2 cells. Thus, introduction of an ORF50 expression plasmid is sufficient to drive the lytic cycle to completion in cultured PEL cells.

Antibodies to Butyrate-Inducible Antigens of Kaposi's Sarcoma–Associated Herpesvirus in Patients with HIV-1 Infection

BACKGROUND The recent identification in patients with Kaposis sarcoma of DNA sequences with homology to gammaherpesviruses has led to the hypothesis that a newly identified virus, Kaposis sarcoma-associated herpeslike virus (KSHV), has a role in the pathogenesis of Kaposis sarcoma. We developed serologic markers for KSHV infection. METHODS KSHV antigens were prepared from a cell line (BC-1) that contains the genomes of both KSHV and the Epstein-Barr virus (EBV). We used immunoblot and immunofluorescence assays to examine serum samples from 102 patients with human immunodeficiency virus type 1 (HIV-1) infection for antibodies to KSHV-associated proteins and to distinguish these antibodies from antibodies to EBV antigens. A positive serologic response was defined by the recognition of an antigenic polypeptide, p40, in n-butyrate-treated BC-1 cells and by the absence of p40 recognition in untreated BC-1 cells or EBV-infected, KSHV-negative cells. The detection by the immunofluorescence assay of 10 to 20 times more antigen-positive cells in n-butyrate-treated BC-1 cells than in untreated cells was considered a positive response. RESULTS Antibodies to the p40 antigen expressed by chemically treated BC-1 cells were identified in 32 of 48 HIV-1-infected patients with Kaposis sarcoma (67 percent), as compared with only 7 of 54 HIV-1-infected patients without Kaposis sarcoma (13 percent). These results were confirmed by an immunofluorescence assay. The positive predictive value of the serologic tests for Kaposis sarcoma was 82 percent, and the negative predictive value 75 percent. CONCLUSIONS The presence of antibodies to a KSHV antigenic peptide correlates with the presence of Kaposis sarcoma in a high-risk population and provides further evidence of an etiologic role for KSHV.

Generalized Lymphadenopathy in Homosexual Men

The cases of 90 homosexual or bisexual men with generalized lymphadenopathy were studied by epidemiologic, clinical, pathologic, immunologic, and genetic methods. The patients ranged in age from 20 to 52 years and had histories of multiple sexually transmitted diseases and both recreational and prescription drug use. Histologically, their lymph nodes showed three patterns: explosive follicular hyperplasia; follicular involution with expansion of the paracortical area; and a mixed pattern of follicular hyperplasia and follicular involution in the same lymph node. The frequency of HLA-DR5 was significantly increased in these patients (p less than 0.005) compared with that in controls. All patients had impaired cell-mediated immunity. Opportunistic infections, lymphomas, or Kaposis sarcoma subsequently developed in 15 patients who had had severe immune dysfunction for the previous 3 to 13 months. We suggest that generalized lymphadenopathy is part of the spectrum of a disorder manifested by acquired immunodeficiency, opportunistic infections, Kaposis sarcoma, and malignant lymphomas.

Progressive lymph node histology and its prognostic value in patients with acquired immunodeficiency syndrome and AIDS-related complex☆

Seventy-four sequential lymph node biopsies from 30 acquired immunodeficiency syndrome (AIDS)/AIDS-related complex (ARC) patients showed temporal histologic progression from explosive follicular hyperplasia (EFH) to mixed follicular hyperplasia/involution (mixed) to follicular involution (FI) to lymphocyte depletion (LD). This histologic progression correlated with symptoms, development of opportunistic infections (OI), and mortality. At initial biopsy, only 50% of the AIDS/ARC patients with EFH/mixed compared to 100% with FI/LD were symptomatic with weight loss, night sweats, diarrhea, fever, or fatigue. 31% of ARC patients with EFH and 63% with FI developed an OI in a median of 69 months and 5 months, respectively; 86% with LD had a concurrent or previous OI. Ninety percent of ARC patients progressing to FI/LD died; 85% of those persisting with EFH/mixed remained alive 18 to 50 months after initial biopsy. AIDS patients with EFH lived twice as long as those with FI/LD. Progressive histology did not correlate with lymphoma. The number of ARC patients developing Kaposis sarcoma was too small to draw definitive conclusions.

Dapsone, Trimethoprim-Sulfamethoxazole, and the Acquired Immunodeficiency Syndrome

Excerpt To the editor: Pneumocystis pneumonia occurs in about 60% of patients with the acquired immunodeficiency syndrome (AIDS) (1), and in many may recur. However, therapy with either trimethopri...

Risks with Danazol in the Acquired Immunodeficiency Syndrome

Excerpt To the editor: Recently, danazol (Danocrine; Winthrop Laboratories, New York, New York) has been reported to decrease the need for transfusions of plasma products in persons with classic he...

The Acquired Immunodeficiency Syndrome

Excerpt To the editor: deShazo and associates (1) have shown deficient cell-mediated immunity in asymptomatic hemophiliac patients and abnormal OK T4/T8 ratios but normal mitogenic responses in fiv...