Aging is associated with increased proliferation and decreased apoptosis in the colonic mucosa.

Although the incidence of colon cancer increases with advancing age, reasons for this increase are not fully understood. Earlier studies have demonstrated that in Fischer-344 rats, aging is associated with increased crypt cell production in the colon, an event considered to be central to the initiation of carcinogenesis. Apoptosis also plays a critical role in the development and progression of colon cancer. Therefore, we have examined the age-related changes in proliferation and apoptosis in the colonic mucosa of 4-5, 12-14, and 22-24 month-old Fischer-344 rats. We have observed that proliferative activity in the colon, as assessed by proliferating cell nuclear antigen immunoreactivity, is higher (50-80%) in 12-14 and 22-24 month-old rats than in their 4-6 month-old counterparts. In contrast, the number of apoptotic cells, (as determined by TdT-mediated dUTP nick-end labeling assay) in the colonic mucosa of 12-14 and 22-24 month-old rats are considerably lower (50-60%) than in 4-6 month-old animals. These changes are accompanied by a concomitant reduction (75%) in pro-apoptotic Bak and stimulation (200%) of anti-apoptotic Bcl-xL levels. Since activation of caspases is associated with initiation and maintenance of apoptosis, we also analyzed the levels of pro and active forms of caspase-3, 8 and 9. The levels of active forms of caspase-3, 8 and 9 are found to be considerably (60-80%) lower in the colonic mucosa of 22-24 month-old rats, compared to their younger counterparts. This is accompanied by decreased cleavage of poly(ADP-ribose) polymerase, a substrate for caspases. In conclusion, our data show that aging enhances proliferation, but attenuates apoptosis in the colonic mucosa. These changes may partly be responsible for the age-related rise in colorectal cancer.

Candidate recombinant vaccine for human B19 parvovirus.

Recombinant baculoviruses were used to produce human B19 parvovirus empty capsids composed of only VP2 and VP2 capsids containing 4%, 25%, 35%, or 41% VP1 protein. Immunogenicity of the purified capsids, formulated with or without adjuvant, was evaluated in mice, guinea pigs, and rabbits. Sera were analyzed for total anti-B19 parvovirus antibodies, antibodies specific to the region unique to the VP1 capsid protein, and virus neutralizing antibodies. A relationship was observed between the development of antibodies specific to sequences unique to the VP1 protein and virus neutralization. The polypeptide composition of the empty capsid immunogens appeared to be important for elicitation of potent virus neutralizing activity. VP2 capsid immunogens devoid of VP1 protein, or consisting of only 4% VP1, the composition of naturally occurring virions, were generally poor at eliciting high levels of virus neutralizing activity. Capsids consisting of > or = 25% VP1 protein efficiently and consistently provoked vigorous B19 virus neutralizing responses. Recombinant empty capsids enriched for the VP1 protein should serve as the basis for a human B19 parvovirus vaccine.

Estimated fetal weight in the detection of the small-for-menstrual-age fetus.

The purpose of this study was to assess the value of calculated fetal weight in the detection of the small-for-menstrual-age fetus. An ultrasound screening scan was performed on 1624 singleton pregnancies at 30 weeks to 36 weeks, menstrual age. Head, abdomen, and femur diaphysis measurements were recorded and used to estimate fetal weight. These and other more widely used parameters were used to predict birth weight below the 10th percentile for menstrual age. Estimated fetal weight at 34 weeks achieved sensitivity of 100% and specificity of 70%, the best result for any parameter. Specificity is improved using growth measurements.