AlvinE. Friedman-Kien

Human herpesvirus-like nucleic acid in various forms of Kaposi's sarcoma

The association between a new human herpesvirus-like agent and various forms of Kaposis sarcoma was examined by PCR. The DNA sequences of this agent were detected in 7 of 8 classic Kaposis sarcoma specimens, 12 of 12 AIDS-associated specimens from the United States, and 7 of 10 specimens from African endemic Kaposis sarcoma. Polymorphism of the herpesvirus-like DNA in the Kaposis tissue from different populations was observed by both single-strand conformational polymorphism and direct sequencing. Furthermore, the presence and expression of the virus was detected in some Kaposis tumours by Southern and northern blotting. This herpesvirus may be involved in the pathogenesis of different kinds of Kaposis sarcoma seen among distinct and unrelated populations.

RISK FACTORS FOR KAPOSI'S SARCOMA IN HOMOSEXUAL MEN

An investigation of 20 homosexual men with histologically confirmed Kaposis sarcoma and 40 controls revealed significant associations between Kaposis sarcoma and use of a number of drugs (amyl nitrite, ethyl chloride, cocaine, phencyclidine, methaqualone, and amphetamine), history of mononucleosis, and sexual activity in the year before onset of the disease. Patients with Kaposis sarcoma also reported substantially higher rates of sexually transmitted infections than did controls. Multivariate analysis indicated independent significant associations for amyl nitrite and sexual activity and showed use of phencyclidine, methaqualone, and ethyl chloride to be non-significant. Evaluated at the median exposure for patients, the analysis yielded risk-ratio estimates of 12.3 for amyl nitrite (95% confidence limits 4.2, 35.8) and 2.0 for sexual activity (95% confidence limits 1.3, 3.1).

EPITHELIOID ANGIOMATOSIS: A DISTINCT VASCULAR DISORDER IN PATIENTS WITH THE ACQUIRED IMMUNODEFICIENCY SYNDROME OR AIDS-RELATED COMPLEX

Unusual cutaneous vascular neoplasms distinct from Kaposis sarcoma were observed in five patients with the acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-1 infection. The cutaneous lesions were solitary or multiple papules and nodules. In some patients the lesions also affected internal organs. Histologically the neoplasms were composed of proliferating blood vessels and cells with epithelioid features. Immunoperoxidase studies of one lesion showed that the cells expressed both factor VIII antigen, a maker for endothelial cells, and alpha 1-anti-chymotrypsin, a marker for histiocytes. In some patients the lesions gradually disappeared but in two they were the cause of death, in one case from disseminated intravascular coagulation and in the other from laryngeal obstruction by the tumour.

HPV-16-related DNA sequences in Kaposi's sarcoma.

In the USA, Kaposis sarcoma associated with the acquired immunodeficiency syndrome (AIDS-KS) is ten times more common in homosexual or bisexual men than in heterosexual men with AIDS. One explanation for this finding is that AIDS-KS may be caused by an infectious agent. Because there is a high incidence of human papillomavirus (HPV) infection, especially HPV-16, in homosexual men, we have sought HPV DNA sequences in Kaposis sarcoma. We used the polymerase chain reaction with a primer pair specific for the highly conserved E6 region of HPV-16 to detect HPV-16 homologous DNA fragments in tumour tissues from 97 patients with KS and in KS-derived cell cultures. HPV DNA sequences were found in 11 of 69 KS skin tumours from homosexual men with AIDS-KS, in 3 of 11 KS biopsy specimens from homosexual men who had no clinical or laboratory evidence of HIV-infection, and in 5 of 17 KS skin lesions from HIV-1-negative elderly men and women with classic KS. The same primer pair amplified HPV-16 homologous fragments from two different continuous cell cultures derived from pleural effusion fluid of patients with pulmonary AIDS-KS and two continuous cell cultures derived from KS skin lesions. The findings suggest that HPV-16-related DNA sequences are associated with different forms of KS and may have a role in the pathogenesis of this neoplasm.

PATIENT-APPLIED PODOFILOX FOR TREATMENT OF GENITAL WARTS

In a double-blind trial, 0.5% podofilox (podophyllotoxin) or placebo was applied by patients to their own genital warts in up to four treatment cycles. At some time during the study, 25 of the 56 podofilox treated patients and none of the 53 placebo group were completely wart-free. At the end of the treatment, 73.6% of the original warts in podofilox treated patients were gone compared with only 8.3% of those in the placebo group (mean percentage of total original wart area was reduced by 82.3% compared with 4.2%). 82% of the treated warts in the podofilox group and 13% in the placebo group had resolved at 6 weeks. Recurrence was observed in 34% of the previously resolved warts. Consistent with this rate of recurrence, new warts developed in a third of the subjects in each group at sites remote from the treatment site. There were no systemic adverse reactions, although transient inflammation, erosion, pain, and burning were common.

HTLV-I-specific antibody in AIDS patients and others at risk

Serum samples from 440 acquired immunodeficiency syndrome (AIDS) patients or individuals at risk for AIDS were examined by the enzyme-linked immunosorbent assay technique for antibodies to HTLV-I core proteins. Specific antibodies were detected in 7% of AIDS patients, 7% of patients with lymphadenopathy, 0% of healthy homosexual men, and 12% of healthy Haitians. When findings in homosexual men were analysed separately, the prevalence for homosexual men with lymphadenopathy was 7% and for homosexuals with AIDS, 6%. Antibody titres ranged from 77 to 74 000. The antibody-positive cases included intravenous drug users, a Haitian AIDS patient, a recipient of multiple blood transfusions, and homosexual men. Haemophiliacs were not examined. Although HTLV-I-specific antibodies are more prevalent in AIDS patients than in healthy US donors, the difference is not sufficient to suggest an association of HTLV-I with the disease. The low rate may indicate an opportunisitic infection of AIDS patients by HTLV-I, or a crossreaction with the recently described HTLV variant, HTLV-III, believed to be the aetiological agent of AIDS. Whether HTLV-I normally exerts immune suppressive effects in vivo with biological consequences remains to be determined.

IgG antibodies to HIV-1 in urine of HIV-1 seropositive individuals.

The observation of antibodies to the human immunodeficiency virus type 1 (HIV-1) in the urine of HIV-1 positive individuals has been expanded in a US study by examining the immunoglobulin content of urine from 80 HIV-1 seropositive individuals with no clinical or laboratory evidence of renal dysfunction. IgG components were demonstrated electrophoretically in 54 of the urines and all 54 samples displayed immunological reactivity against anti-gamma heavy-chain antiserum. The prognostic significance of an apparently high frequency of light-chain immunoglobulin dimers in the urine of HIV-1 seropositive individuals is unknown. These observations suggest a potential diagnostic screen for detecting antibodies to HIV-1 in urine which may be useful when blood specimens are not available.

Evaluation of the tumorigenic and angiogenic potential of human fibroblast growth factor FGF3 in nude mice

Abstract Recently, the expression of fibroblast growth factor 3 (FGF3) was found in 55% of human Kaposis sarcoma (KS) tumor tissues examined, while almost no expression of FGF3 was found in normal skin. To further these studies, human FGF3 cDNA were constructed by the overlap-extension method. The proteins translated from two FGF3 cDNA, which differ only in the sequences preceding the AUG presumed to be the initiation codon, were shown to have the same molecular mass. This result suggests that translation of human FGF3, which is different from mouse FGF3, begins only at the AUG site. The human FGF cDNA was transfected into NIH3T3 cells. The NIH 3T3 cells transformed by FGF3 were then injected subcutaneously into athymic nude mice. Nodular lesions developed at the injection sites in all seven mice injected with the F3-1 cell clone, which showed high expression of FGF3, and in two out of six mice injected with the F3-2 cell clone, which expressed a low level of FGF3. Histopathological features of these tumors contained fascicles of spindle-shaped cells surrounding irregular endothelial lined vascular clefts, similar to those observed in human KS lesions. Immunohistochemical staining for factor V111 antigen revealed reactivity in multiple areas, especially in abundant vascular structures of the tumor sections examined. The expression of FGF3 together with the FGF receptors FGFR1, FGFR2, and FGFR3, was detected in the mouse tumors by Northern blot analysis. Our results indicate that tumors induced by FGF3-transformed NIH3T3 cells show some similarities to human KS tumors. In conclusion, our results demonstrate the potential tumorigenic and angiogenic role of human FGF3.