Faculty Bibliography

Human herpesvirus 8 (HHV-8) has been proposed as a sexually transmitted etiologic agent of Kaposi's sarcoma (KS). In this study, by use of a sensitive polymerase chain reaction assay, HHV-8 DNA was detected in the skin lesions (92%), normal skin (23%), peripheral blood mononuclear cells (PBMC) (46%), plasma (7%), saliva (37%), and semen (12%) but not stool samples from KS patients. The average number of HHV-8 copies per microgram of positive target DNA was 64, 000, 9000, 40, 33,000, and 300 for skin, PBMC, plasma, saliva, and semen samples, respectively. Only 1 non-KS donor sample, of saliva, was positive for HHV-8. Sequencing showed 5% divergence among HHV-8 strains. The data suggest that saliva may be more important than semen or stool in the sexual transmission of HHV-8. The relatively high prevalence of HHV-8 in PBMC raises the question as to why there is no evidence for bloodborne virus transmission

The skin is affected in virtually all patients with HIV infection. Many articles and several books have been published that deal with these disorders for a number of reasons. First, cutaneous disease may serve as the initial or only problem that the patient suffers for much of the course of the HIV infection. Second, serious opportunistic infections may present for the first time in the skin, so that a skin lesion may be a harbinger of the patient's having a life-threatening illness. Third, skin disorders in these patients may appear unusual and hence may not be accurately diagnosed by clinical inspection alone. Furthermore, response to treatment may be poorer than expected. Thus, skin diseases in the HIV-infected patient are important and, in some cases, may be the most debilitating element of the patient's condition

A human herpesvirus-8 (HHV-8) enzyme-linked immunosorbent assay (ELISA) with a whole virus lysate as antigen was developed and used to measure the seroprevalence rate and levels of IgG antibodies to HHV-8 in sera/plasma of various patient groups and blood donors. The virus antigen was prepared from the KS-1 cell line, which produces lytic virus, and therefore contains a broad array of viral proteins. Seroprevalence studies using this ELISA showed the following: 10 of 91 blood donors (11%) had an average HHV-8 antibody titer of 118; 67 of 72 (93%) classic Kaposi's sarcoma (KS) patients were positive with an average titer of 14,111; and 57 of 62 (92%) KS/human immunodeficiency virus (HIV) patients were positive with an average titer of 4,000. A study on a very limited number of serial serum samples from patients before and after diagnosis with KS showed highly elevated antibody titers to HHV-8 virus after KS lesions developed. Preliminary data show that 50% of the sera from HIV-1(+) homosexual patients contain IgG antibodies to HHV-8 suggesting that this population is at high risk for developing KS. Antibody results correlated well with the confirmatory immunofluorescent assays (IFA) using KS-1 cells as the substrate. This HHV-8 IgG antibody detection ELISA is sensitive and specific and does not cross-react with Epstein-Barr virus (EBV) or other human herpesviruses. The results of this HHV-8 antibody survey suggest that this rapid ELISA assay can be used to screen large numbers of sera to find those at risk for developing KS

PURPOSE: Kaposi's sarcoma (KS), the most common neoplasm in patients with AIDS, is a significant clinical problem for which current therapies are frequently unsatisfactory. We conducted a randomized phase III clinical trial to compare the efficacy and toxicities of a new form of therapy, pegylated-liposomal doxorubicin, with standard combination chemotherapy in patients with advanced AIDS-related KS (AIDS-KS). PATIENTS AND METHODS: Two hundred fifty-eight patients with advanced AIDS-KS were randomly assigned to receive either pegylated-liposomal doxorubicin (20 mg/m2) or the combination of doxorubicin (20 mg/m2), bleomycin (10 mg/m2) and vincristine (1 mg) (ABV) every 14 days for six cycles. Standard response criteria, toxicity criteria, and predefined indicators of clinical benefit were examined to evaluate outcomes. RESULTS: Among 133 patients randomized to receive pegylated-liposomal doxorubicin, one achieved a complete clinical response and 60 achieved a partial response for an overall response rate of 45.9% (95% confidence interval [CI], 37% to 54%). Among 125 patients randomized to receive ABV, 31 achieved a partial response (24.8%; 95% confidence interval [CI], 17% to 32%). This difference was statistically significant (P < .001). In addition to objective responses, prospectively defined clinical benefits and toxicity outcomes also favored pegylated-liposomal doxorubicin. CONCLUSION: Pegylated-liposomal doxorubicin is more effective and less toxic than the standard combination chemotherapy regimen ABV for treatment of AIDS-KS

BACKGROUND: Molluscum contagiosum is usually a self-limited benign viral disease in children and young adults. In patients with acquired immunodeficiency syndrome (AIDS), however, the infection is often widespread, disfiguring, and recalcitrant to conventional therapy. OBJECTIVE: A treatment modality for widespread, recurrent molluscum contagiosum is necessary that is effective, safe, and simple. METHODS: Widespread molluscum contagiosum recalcitrant to conventional therapy in a patient with AIDS was treated with the 585-nm pulsed dye laser. RESULTS: There was a significant reduction in the number of molluscum contagiosum lesions following a single treatment with the pulsed dye laser. Treated-areas remained disease-free after 4 months. No complications were associated with the procedure. CONCLUSION: Pulsed dye laser treatment may offer another therapeutic modality that is effective and safe in the treatment of widespread and recurrent molluscum contagiosum

The recently discovered human herpes virus 8 (Kaposi's sarcoma-associated herpes virus) has been implicated in the pathogenesis of Kaposi's sarcoma. Using polymerase chain reaction we detected DNA sequences of this herpes virus in 11 of 14 biopsy specimens from Kaposi's sarcoma in Norwegian patients, including the immunosuppressive therapy-related type (3 of 3), the HIV-related type (4 of 5), and the classical type (4 of 6). The results support the hypothesis of a role for human herpes virus 8 in all types of Kaposi's sarcoma independent of geographical area

Recently, the expression of fibroblast growth factor 3 (FGF3) was found in 55% of human Kaposi's 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

Alteration of the p53 gene is the most frequent event reported in human cancer, and p53 mutations have been observed in various neoplasms, including certain forms of skin cancer. Therefore, we postulated that p53 may also be involved in Kaposi's sarcoma associated with AIDS (AIDS-KS). Expression of the p53 gene was examined in freshly isolated tumor biopsy specimens from 15 patients with AIDS-KS. p53 mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in both the AIDS-KS tumors and in normal skin control samples. p53 protein was detected in 4 of the 15 AIDS-KS specimens by immunohistochemical staining. Single-strand conformation polymorphism analysis PCR-products (PCR-SSCP) was used for detection of mutations of the p53 gene. One of the p53 positive AIDS-KS samples showed mobilized shifts in exon 6 suggestive of a mutation. Sequencing data showed the mutation to be located in codon 210. We examined other mechanisms that could stabilize p53 protein. SV40 large T antigen and adenovirus E1B protein were not found in the AIDS-KS specimens. MDM2, a p53-binding protein, was also detected in five of the AIDS-KS specimens, two of which also contained p53-positive cells. These observations suggest that the tumor suppressor gene p53 may be involved in the pathogenesis of AIDS-KS