Clinical presentation of minimally invasive and in situ squamous cell carcinoma of the anus in homosexual men.

From January 1988 to December 1993, we identified six men with minimally invasive (stage I) squamous cell carcinoma of the anus and 10 men with anal carcinoma in situ (CIS). Of the six patients with invasive carcinoma, four were infected with human immunodeficiency virus (HIV), including one with AIDS. Of the 10 patients with CIS, eight were infected with HIV, including four with AIDS. Anal pain and bleeding were the most common symptoms of minimally invasive anal cancer and anal CIS. Anal irritation, burning, or pruritus occurred more frequently in patients with CIS, whereas anal ulcers, masses, or abscesses were more frequent in patients with minimally invasive cancer. Several patients with CIS had a discrete area of leukoplakia in the anal canal or a pigmented plaque of the anus and anal canal. These lesions were not observed in patients with minimally invasive anal cancer. The symptoms and signs of early-stage anal cancer in men at risk for developing HIV infection or men infected with HIV often resemble those of other common anorectal diseases in homosexual men. Anal cancer in HIV-infected men is not limited to those individuals with AIDS.

Application of an objective biological assay of human interferons to clinical specimens and a survey of a normal population.

A rapid, quantitative, and nonsubjective method of interferon assay is described, which can be readily applied to clinical specimens. Automated data acquisition and data reduction allowed a significant increase in volume per unit of time over existing methodologies. Plasma always yielded higher (usually 2:1) interferon values than did serum obtained simultaneously. Ranges of interferon levels in plasma in normal control populations are reported as well as ranges for clinical virology laboratory technicians and patients with terminal malignancies or collagen vascular diseases.

Antidotes for gold (sodium bis[thiosulfato]gold[I]) intoxication in mice.

Eight compounds were examined to determine their relative efficacy as antidotes in acute gold intoxication in mice after the intraperitoneal injection of 200 mg/kg of Na3 [Au(S2O3)2] X 2H2O. Of the compounds examined, 2,3 dimercaptosuccinic acid was the most effective antidote. It was noted that with D-penicillamine those animals which did not survive died sooner (in a matter of hours) than the corresponding control animals which had received no antidote (about 3 days). In subsequent experiments in which Na3 [Au(S2O3)2] X 2H2O was administered at the lower level of 140 mg/kg, 2,3 dimercaptosuccinic acid showed itself to be capable of reducing kidney gold levels by a factor of about 5 and liver gold levels by a factor of approximately 2.

Pleiotropic activities of human interferons are mediated by multiple response pathways.

Among the pleiotropic effects of human interferon are the inhibition of viral replication, the activation of natural killer cells, and the inhibition of cellular growth. Oxyphenbutazone, a nonsteroidal antiinflammatory agent, is a potent inhibitor of the antiviral activity of human alpha and beta interferons as determined by cytopathic effect and vesicular stomatitis virus synthesis and release in human foreskin fibroblasts. The inhibition of interferon activity is dose dependent with maximal inhibition at 25-50 microM and minimal inhibition at 1 microM. In contrast, oxyphenbutazone at concentrations as high as 100 microM has no effect on the activation of natural killer cells by human interferon. Similarly, oxyphenbutazone has no inhibitory effect on interferon-induced antigrowth activity in the human breast carcinoma cell line MDA-MB-231. This cell line is sensitive to oxyphenbutazone inhibition of interferon-induced antiviral activity in vitro. In another human cell line, the vulvar carcinoma A431, oxyphenbutazone apparently augments the antigrowth activity of interferon. Although oxyphenbutazone inhibits the fatty acid cyclooxygenase enzyme in these systems, other inhibitors of cyclooxygenase fail to inactivate the antiviral activity of human interferon. Thus, oxyphenbutazone appears to inhibit the interferon antiviral cascade at a site distinct from prostaglandin biosynthesis. Moreover, the failure to inhibit natural killer cell activation or cellular antigrowth effects of human interferon suggests a pathway different from that associated with the antiviral effect of human interferon.

A functional cyclooxygenase enzyme is not required for mediation of the pleiotropic effects of human alpha or beta interferon.

Aspirin, indomethacin, and phenbutazone at 50 microM concentration inhibit cyclooxygenase in cultured human foreskin fibroblasts as evidenced by the suppression of the major prostaglandin species which accumulate in the culture medium. In contrast to data reported for mouse interferon on target mouse cells, these agents have no effect on the induction of antiviral activity by human alpha or beta interferons. Similarly, these agents have no effect on interferon induced inhibition of cell growth in vitro or on interferon induced natural killer cell activity.

Spontaneous and interferon resistant natural killer cell anergy in AIDS.

The acquired immunodeficiency syndrome (AIDS) is characterized by severe unrelenting opportunistic infections and/or Kaposi's sarcoma associated with a dysfunction of cell mediated immune responses. In addition to cutaneous anergy and inversion of T-helper/inducer to T-suppressor cell ratios usually observed in AIDS, we have observed in three AIDS cases with multiple opportunistic infections that spontaneous and interferon (IFN) stimulated natural killer (NK) cell activity against K-562 cells is absent or severely depressed as compared to controls. Spontaneous and IFN stimulated NK cell activity in promiscuous male homosexual controls was similar to that observed in heterosexual controls. The control subjects had T-helper:T-suppressor ratios ranging from 1.1 to 2.4 in contrast to the AIDS subjects who had typical inverted ratios of T-cells ranging from 0.17 to 0.54. HNK-1, a monoclonal antibody that identifies NK and antibody-dependent cytotoxic cells, marked 3-22% of peripheral blood lymphocytes from AIDS patients in comparison to 8-38% of lymphocytes from controls. A larger series will be required in order to ascertain the true incidence of NK cell anergy in AIDS and whether or not subgroups exist based on the association of Kaposi's sarcoma in the disease process.