Publications

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.

Abnormalities in calcium homeostasis have been reported in Alzheimer's disease (AD) and in the neurofibrillary tangle disorders of amyotrophic lateral sclerosis and parkinsonism-dementia occurring in the Pacific. In order to more fully evaluate calcium physiology in AD, we analyzed the size of pineal and choroid plexus calcifications, using X-ray computed tomography, in 23 patients with probable AD and 18 healthy age-matched control subjects. The area occupied by calcification was measured from hard copies of the data by two independent observers who were blind to the diagnosis. There were no differences in the areas occupied by pineal or choroid plexus calcifications between the two groups. These data suggest that AD is not accompanied by alternations in intracranial calcium deposition in pineal gland or choroid plexus.

The relation between left atrial dimension measured by M-mode echocardiography and systemic embolization after valve replacement was examined prospectively among 397 patients with a prosthetic valve enrolled in the Department of Veterans Affairs Cooperative Study on Valvular Heart Disease. Baseline characteristics including several measures of left atrial enlargement were compared for 31 patients who developed systemic embolism and 366 who did not develop embolism during a 5 year follow-up period. Variables that were significantly related to left atrial dimension or systemic embolization in univariate analyses were included with several others in a multiple logistic regression model. The incidence rate of systemic embolism was more than three times higher after mitral valve replacement than after aortic valve replacement (4.4 and 1.3 per 100 patient-years, respectively); this difference persisted after adjustment for other factors. Univariate analysis indicated a threefold higher incidence of systemic embolism in patients with a left atrial dimension greater than or equal to 4 cm compared with that in patients with a dimension less than 4 cm (3 versus 1 per 100 patient-years, respectively). However, when the effect of valve location (mitral versus aortic) was taken into account using either univariate or multivariate techniques, left atrial dimension was found not to be associated with systemic embolism. In multivariate analysis, atrial fibrillation, age, ejection fraction and location of the prosthetic valve were significantly associated with embolism. Results of this multicenter study suggest that left atrial dimension is not independently related to the development of systemic embolism in patients undergoing valve replacement.

Transcriptional induction of the gene encoding the alpha-subunit of IL-2R has been shown to be mediated by a sequence element (GGGGAATCTCCC) that is homologous to the NF-kappa B-binding site of the kappa Ig gene enhancer. In this report we demonstrate that the induced transcription of this gene by mitogen and by the tax gene product of the type-I human T cell leukemia virus is dependent upon an additional sequence motif (GGGCGTAGC) located approximately 10 bp downstream of the previously identified site. This newly identified motif binds a factor that is present in extracts derived from different cell types and does not appear to be required for basal promoter activity. We conclude that proteins binding at both sites act coordinately, leading to maximal induction of the receptor gene.