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BALB/c mice infected with Leishmania major develop fatal, progressive disease, despite an immune response characterized by expansion of CD4+ T cells in the draining lymph nodes. The immune response has been further characterized by a lack of IFN-gamma mRNA, but increased IL-4 mRNA in lymphoid tissues, and striking elevation of serum IgE. Treatment of infected BALB/c mice with rIFN-gamma at doses shown to be beneficial in other protozoan infections was insufficient to ameliorate L. major infection. In contrast, neutralization of IL-4 by six weekly injections of mAb 11B11 led to attenuation of disease in 100% of animals, and complete cure in 85%. Resolution of disease required the presence of T cells, and recovered mice remained resistant to reinfection at 12 wk. This immunity was adoptively transferable and was dependent on both CD4+ and CD8+ cells. Although administration of anti-IL-4 was associated with fourfold increase in IFN-gamma mRNA in lymph node cells draining the lesion, the coadministration of neutralizing R4 6A2 anti-IFN-gamma mAb had no effect on resistance to disease. This was in marked contrast to resolution of disease in both resistant C57BL/6- and GK1.5-pretreated BALB/c mice that was abrogated by in vivo treatment with anti-IFN-gamma. These data suggest a novel mechanism of cellular immunity established by interference with the development of Th2 cells during infection.

To clarify further the epidemiology of AIDS-related Kaposi's sarcoma (KS) in San Francisco, we reviewed AIDS cases reported to the San Francisco Department of Public Health through August 31, 1990. Of the 7,119 patients reported, 2,346 (33%) had been diagnosed as having KS: 1,716 (73%) as their presenting clinical manifestation of AIDS and 648 (27%) as a later manifestation. Of these 2,364 KS patients, 2,075 (88%) were homosexual or bisexual men without histories of intravenous drug use, and 273 (12%) were homosexual or bisexual intravenous drug users. From 1981 to August 1989, the proportion of AIDS patients presenting with KS declined from 55 to 19% (p less than 0.001). However, the number of patients being diagnosed with KS has increased along with the overall number of AIDS patients, but this increase was less than the increase in number of patients with other opportunistic infections and malignancies. KS patients were less likely than patients without KS to be reported through an active surveillance system and less likely to be found through retrospective reviews of medical records, death certificates, and obituaries. We conclude that the proportion of AIDS patients with KS is continuing to decline in San Francisco and that this decline is not an artifact of the AIDS surveillance system.

To evaluate survival for AIDS patients diagnosed with Kaposi's sarcoma (KS), we calculated survival for 1,015 patients reported in San Francisco between July 1981 and December 31, 1987, representing 22% of total patients reported. These patients had a definitive initial diagnosis of KS, and developed no other diseases within 3 months of diagnosis. Patients were followed prospectively through December 31, 1988. All patients evaluated in this study were men. Survival was evaluated for subgroups based on age, race and ethnicity, year of diagnosis, and transmission category. The median survival for patients diagnosed with KS alone was 17.0 months, with a 5-year survival rate of 8.7%. Poorer prognosis was found for patients with older age at diagnosis and with later year of diagnosis. Proportional hazards analysis indicated that age (p less than 0.001) and year of diagnosis (p less than 0.05) were significant independent predictors of survival, while race or ethnicity and risk group were not.

We identified 277 homosexual and bisexual men diagnosed with acquired immune deficiency syndrome (AIDS) whose estimated human immunodeficiency virus (HIV) seroconversion dates, ranging from 1977-85, could be well approximated. These men were from a cohort of 6,705 homosexual and bisexual men originally recruited for studies of sexually transmitted hepatitis B in San Francisco in 1978-80. We compared the time from HIV seroconversion to the initial disease diagnostic of AIDS (AIDS latency period) with the time from first AIDS diagnosis to death (AIDS survival time) and found no significant overall correlation between latency period and survival time. Both Kaplan-Meier and Cox proportional hazard stepwise analyses found the initial AIDS diagnosis to be significantly associated with latency period, with individuals first diagnosed with Kaposi's sarcoma (KS) having a shorter latency but longer survival than those first diagnosed with Pneumocystis carinii pneumonia (PCP) or other AIDS diagnoses. Individuals with KS tended to be diagnosed earlier in the epidemic compared to those with PCP and other non-KS diagnoses. The AIDS survival time was significantly associated with the initial AIDS diagnosis but not with the estimated year of seroconversion, the year of first AIDS diagnosis, age at seroconversion, or racial/ethnic group. The information presented here on the relationship between the AIDS latency period and survival times suggests a model for the pathogenesis of HIV infection in which there is continual deterioration of the immune system. The wider use of antiviral and prophylactic therapies both preceding and following a diagnosis of AIDS may change this model as both latency and survival times are improved.

The changing epidemiology of Kaposi's sarcoma (KS) and possible explanations for this change were analyzed using data from a well-characterized cohort of homosexual and bisexual men. Among 1,341 men with AIDS, the proportion presenting with KS declined from 79% in 1981 to 25% in 1989. For 250 men whose date of HIV seroconversion could be well characterized, persons presenting with KS had a shorter interval from HIV seroconversion to AIDS diagnosis than other AIDS patients without KS (mean = 77 vs. 86 months). Among 182 men who were interviewed prior to a diagnosis of AIDS, men with and without KS did not significantly differ with respect to number of sex partners, a history of certain sexually transmitted or enteric diseases, use of certain recreational drugs (including nitrite inhalants), or participation in certain specific sexual practices. The decline in KS may at least partly be due to a shorter latency period from infection to disease. Although cofactors for the development of KS may exist, many previously hypothesized agents were not supported by this analysis.

We used death certificate data for San Francisco residents from 1979 to 1986 to calculate the number of deaths and years of potential life lost before age 65 (YPLL) for leading causes of death. Acquired immune deficiency syndrome (AIDS)-related deaths were defined as including cytomegalovirus infection (ICD-9 078.5); cryptococcal infection (ICD-9 117.5); Pneumocystis carinii pneumonia (ICD-9 136.3); other malignant neoplasms of the skin, site unspecified (ICD-9 173.9); deficiency of cell-mediated immunity (ICD-9 279.1); and unspecified immunity deficiency (ICD-9 279.3). These deaths increased from 5 (0.1% of all deaths) in 1979 to 534 (6.6%) in 1986. Of the 1,225 deaths caused by AIDS-related diseases during this period, 1,032 (84%) occurred in men aged 20-49 years. AIDS-related deaths increased between 1979 and 1986 from 0 to 44 (25% of all deaths), 0 to 257 (44%), and 0 to 150 (35%) in men aged 20-29 years, 30-39 years, and 40-49 years, respectively. In 1986, AIDS-related diseases were the third leading cause of deaths and the leading cause of YPLL among male San Francisco residents.

Loading of tissue macrophages with dialysis-tubing-derived particles may occur during chronic haemodialysis. Previous studies have demonstrated that these particle-laden macrophages release significant quantities of prostaglandins. In these experiments, the effects of dialysis-tubing-particle loading on the release of the central inflammatory mediator, interleukin 1 (IL 1), was examined. Rats received daily injections of silicone or polyvinylchloride (PVC) particles, and were compared to animals given saline alone. The silicone and PVC groups received a total of 3 x 10(9) particles over a 4-week period. Non-stimulated peritoneal macrophages from control animals released a median of 4.1 (range 1.2-10.3) U IL 1 per 10(6) cells. In contrast, macrophages from silicone- and PVC-loaded animals spontaneously released high levels of IL 1 (median 21.8; range 10-36.7) and 94 (range 36-336) U per 10(6) cells respectively). Following in vitro stimulation with bacterial lipopolysaccharide (LPS), peritoneal macrophages from silicone- and PVC-treated animals released large amounts of IL 1 (median 538 (range 359-2017) U and median 653 (range 326-1134) U per 10(6) cells, respectively) as compared to LPS-stimulated macrophages from control animals (median 332 (range 130-306) U per 10(6) cells]. Zymosan or LPS stimulation of splenic cells from silicone- and PVC-loaded animals also secreted increased quantities of IL 1 as compared to controls. The chronic loading of tissue macrophages in dialysis patients with tubing-derived particles may result in augmented release of IL 1, with subsequent activation of inflammatory processes.