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Invasive cervical cancer in young women. Clinicopathologic correlation and demonstration of human papillomavirus by in situ hybridization.
It has been suggested that invasive cervical carcinoma is biologically more aggressive in young patients than in older patients. The clinicopathologic characteristics and human papillomavirus (HPV) status of women < or = 35 years of age with invasive cervical carcinoma treated at Emory University Hospital from 1985-1989, were evaluated in a retrospective study. The group consisted of 23 patients, 35% of all patients with invasive cervical carcinoma. Age at diagnosis, clinical stage, histologic classification, lymph node status, treatment and clinical follow-up were obtained from medical records. HPV status was evaluated by colorimetric in situ hybridization for HPV types 6, 11, 16, 18, 31, 33 and 35 in archival formalin-fixed paraffin-embedded tumor material available from 16 of the patients. This study found that the young patients had lower survival and greater extent of disease than predicted by clinical staging. The rate of detection of HPV (69% positive) and HPV typing (type 16 predominated) in these young patients showed no difference from other series of cervical carcinomas from all age groups. Although a higher proportion of patients who died of disease had HPV-negative tumors (3/7, 43%) than those patients who were alive and free of disease (2/9, 22%), this difference was not statistically significant (P = .73, Fisher's Exact T-Test).
Effects of calorie restriction and aging on the expression of antioxidant enzymes and ubiquitin in the liver of Emory mice.
We studied the effect of age and calorie restriction on the expression of genes involved in antioxidant defenses in livers of young (4.5-6 months) and old (22 months) Emory mice fed a control (C) or restricted (R) diet. Specifically examined were catalase (CAT), glutathione peroxidase (Gpx), Cu/Zn and Mn superoxide dismutase (Cu/ZnSOD and MnSOD). As an indicator of oxidative damage to the tissues we measured lipid peroxidation. As indicators of oxidative stress we determined ubiquitin mRNA levels and endogenous high molecular weight (HMW) ubiquitin conjugates. Lower mRNA levels of ubiquitin (P < 0.05), CAT (P < 0.01) and Gpx (P < 0.01) were observed in tissues from young R versus C animals. The old C group had a lower CAT mRNA level (P < 0.0001) compared with young C. In the R group, age did not affect the CAT mRNA levels or Gpx mRNA levels; however, ubiquitin mRNA levels were higher (P < 0.05). No significant changes in Cu/Zn or MnSOD mRNA were observed with age or diet. Cu/ZnSOD protein levels were lower in the young R at 4.5 months (P < 0.05) than young C, and higher in the old R group versus old C (P < 0.05). CAT protein levels were higher in the old C versus old R (P < 0.05). Changes of HMW ubiquitin conjugates with age r diet were not significant. Of the four groups, the old R group showed the highest levels of lipid peroxidation.
Aging, calorie restriction and ubiquitin-dependent proteolysis in the livers of Emory mice.
Calorie restriction (R), the only known method to delay the aging process and extend mean and maximal lifespan, has been shown to delay the age-related decline in protein degradation. There are several proteolytic pathways. The ubiquitin- and ATP-dependent proteolytic pathway (UPP) is frequently associated with degradation of damaged abnormal and/or regulatory proteins. We examined the effect of aging and R on supernatants of livers taken from young (4.5 months) and old (23 months) Emory mice. Aging was associated with increased levels of endogenous ubiquitin conjugates, enhanced ability to form high molecular weight conjugates and ubiquitin activating (E1) and ubiquitin conjugating (E2) activity in the control (C) liver supernatants. The age-related increase in levels of endogenous ubiquitin conjugates in liver appears to be primarily due to increased E1 and E2 activities. R prevented the age-related increase in E1 and E2 activity, and thus prevented the age-related increase in levels of ubiquitin conjugates. In spite of the age-related increase in ubiquitin conjugates, no age-related changes in ubiquitin-dependent proteolytic pathway were observed in the C animals. R was associated with an enhanced ability (130%) to degrade beta-lactoglobulin by the ubiquitin-dependent proteolytic pathway in livers from 4.5-month-old animals relative to age-matched C livers. However, rates of the ubiquitin-dependent degradation of beta-lactoglobulin in the 23-month-old C and R animals were indistinguishable. There were no age- or diet-related differences in the ability to degrade another substrate, oxidized ribonuclease (RNase).