Non-Hodgkin lymphoma is seen in approximately 5% of patients with AIDS. In recent years, the incidence has increased due to an extension of the average lifespan of HIV-infected individuals. In this article we describe the histological and clinical features of 45 patients with HIV-related non-Hodgkin lymphoma seen at the Academic Medical Centre between 1984 and 1991. There were 43 men and 2 women with a median age of 40 years. Most patients had high-grade B-cell lymphoma; 85% had extranodal sites. Prognosis was poor: overall median survival was only 3.8 months.
Accessible and readily utilized software, tables and approximation formulae have been developed to estimate power and sample size for studies of time to event (survival times) when the survival times are assumed to be exponential. These methods can markedly misestimate power when the distribution is Weibull and not exponential. The Weibull distribution with increasing hazard is common in aging research, especially when the whole life span of the subjects is of interest.
There is a considerable variation in individual lifespan among cancer patients with identical diagnosis. We used damped exponential approximation, which includes both single- and double-compartment extension, for radiobiological assessment of survival curves among cases of breast, lung and oro-pharyngeal cancer. It was shown that in certain cases (breast--T2N1-2M0T3N1-2M0 and oro-pharyngeal cancer--T2-4N1-3M0) the curves can be identified with the two compartments which in turn are associated with different rates of mortality.
C57BL/6J mice carrying the Min allele of Adenomatous polyposis coli (Apc) develop numerous adenomas along the entire length of the intestine and consequently die at an early age. This short lifespan would prevent the accumulation of somatic genetic mutations or epigenetic alterations necessary for tumor progression. To overcome this limitation, we generated F(1) Apc(Min/+) hybrids by crossing C57BR/cdcJ and SWR/J females to C57BL/6J Apc(Min/+) males. These hybrids developed few intestinal tumors and often lived longer than 1 year.
Hormesis occurs when a low level stress elicits adaptive beneficial responses that protect against subsequent exposure to severe stress. Recent findings suggest that mild oxidative and thermal stress can extend lifespan by hormetic mechanisms. Here we show that the botanical pesticide plumbagin, while toxic to C. elegans nematodes at high doses, extends lifespan at low doses. Because plumbagin is a naphthoquinone that can generate free radicals in vivo, we investigated whether it extends lifespan by activating an adaptive cellular stress response pathway. The C.
Spinal muscular atrophy (SMA) is the leading genetic cause of early childhood death worldwide and no therapy is available today. Many drugs, especially histone deacetylase inhibitors (HDACi), increase SMN levels. As all HDACi tested so far only mildly ameliorate the SMA phenotype or are unsuitable for use in humans, there is still need to identify more potent drugs. Here, we assessed the therapeutic power of the pan-HDACi JNJ-26481585 for SMA, which is currently used in various clinical cancer trials.
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
The choice of a phenotype is critical for the study of a complex genetically regulated process, such as aging. To date, most of the twin and family studies have focused on broad survival measures, primarily age at death or exceptional longevity. However, on the basis of recent studies of twins and families, biological age has also been shown to have a strong genetic component, with heritability estimates ranging from 27% to 57%.
Leukocyte telomere length is widely considered a biomarker of human age and in many studies indicative of health or disease. We have obtained quantitative estimates of telomere length from blood leukocytes in a population sample, confirming results of previous studies that telomere length significantly decreases with age. Telomere length was also positively associated with several measures of healthy aging, but this relationship was dependent on age.
Exceptional longevity is associated with substantial heritability. The ?4 allele in apolipoprotein E and the linked G allele in rs2075650 of TOMM40 have been associated with increased mortality and the ?2 allele with decreased mortality, although inconsistently. Offspring from long-lived families and spouse controls were recruited at 3 sites in the United States and Denmark. We used generalized estimating equations to compare the likelihood of carrying risk alleles in offspring (n = 2307) and spouse controls (n = 764), adjusting for age, sex, level of education, and family membership.