Dietary patterns, smoking, and subclinical heart disease in women: opportunities for primary prevention from the Framingham Nutrition Studies.

Objectives: To investigate the relationship between a heart-healthy dietary pattern and subclinical heart disease in women, and to identify potential opportunities for primary prevention.

Design: Prospective analysis in which dietary patterns and cardiovascular disease (CVD) risk factors were assessed at baseline. Presence of subclinical heart disease was assessed using carotid atherosclerosis (stenosis >or=25%) measured by ultrasound at 12-year follow-up.

Inducible repair of oxidative DNA lesions in the rat brain after transient focal ischemia and reperfusion.

To determine the role of oxidative DNA damage and repair in brain injury after focal ischemia and reperfusion, the authors investigated DNA base damage and DNA base excision repair (BER) capacity, the predominant repair mechanism for oxidative DNA lesions, in the rat model of temporary middle cerebral artery occlusion. Contents of 8-hydroxyl-2'-deoxyguanosine (8-oxodG) and apurinic/apyrimidinic abasic site (AP site), hallmarks of oxidative DNA damage, were quantitatively measured in nuclear DNA extracts from brains 0.25 to 72 hours after 1 hour of middle cerebral artery occlusion.

Dietary patterns and the odds of carotid atherosclerosis in women: the Framingham Nutrition Studies.

Background: We prospectively examined the relationship between dietary patterns, assessed using cluster analysis and a food frequency questionnaire, and the presence of carotid artery stenosis, a subclinical marker of atherosclerotic disease.

Methods: Analyses were conducted among 1,423 Framingham Study women without cardiovascular disease (CVD) at baseline (1984-1988). Carotid atherosclerosis (stenosis > or =25%) was measured by ultrasound 12 years later.

Age-dependent decline of DNA repair activity for oxidative lesions in rat brain mitochondria.

Endogenous oxidative damage to brain mitochondrial DNA and mitochondrial dysfunction are contributing factors in aging and in the pathogenesis of a number of neurodegenerative diseases. In this study, we characterized the regulation of base-excision-repair (BER) activity, the predominant repair mechanism for oxidative DNA lesions, in brain mitochondria as the function of age. Mitochondrial protein extracts were prepared from rat cerebral cortices at the ages of embryonic day 17 (E17) or postnatal 1-, 2-, and 3-weeks, or 5- and 30-months.

The internal validity of a dietary pattern analysis. The Framingham Nutrition Studies.

Study Objectives: To examine the internal validity of a dietary pattern analysis and its ability to discriminate clusters of people with similar dietary patterns using independently assessed nutrient intakes and heart disease risk factors.

Design And Participants: Population based study characterising dietary patterns using cluster analysis applied to data from the semiquantitative Framingham food frequency questionnaire collected from 1942 women ages 18-76 years, between 1984-88.

Setting: Framingham, Massachusetts.

Induction of caspase-activated deoxyribonuclease activity after focal cerebral ischemia and reperfusion.

Deoxyribonucleic acid fragmentation at nucleosomal junctions is a hallmark of neuronal apoptosis in ischemic brain injury, for which the mechanism is not fully understood. Using the in vitro cell-free apoptosis assay, the authors found that caspase-3-dependent deoxyribonuclease activity caused internucleosomal DNA fragmentation in brain-cell extracts in a rat model of transient focal ischemia. This in vitro deoxyribonuclease activity was completely inhibited by purified inhibitor of caspase-activated deoxyribonuclease protein, the specific endogenous inhibitor of caspase-activated deoxyribonuclease, or by caspase-activated deoxyribonuclease immunodepletion.

Intracellular Bax translocation after transient cerebral ischemia: implications for a role of the mitochondrial apoptotic signaling pathway in ischemic neuronal death.

Activation of terminal caspases such as caspase-3 plays an important role in the execution of neuronal cell death after transient cerebral ischemia. Although the precise mechanism by which terminal caspases are activated in ischemic neurons remains elusive, recent studies have postulated that the mitochondrial cell death-signaling pathway may participate in this process. The bcl-2 family member protein Bax is a potent proapoptotic molecule that, on translocation from cytosol to mitochondria, triggers the activation of terminal caspases by increasing mitochondrial membrane permeability and resulting in the release of apoptosis-promoting factors, including cytochrome c.

Validation of a dietary pattern approach for evaluating nutritional risk: the Framingham Nutrition Studies.

Objective: To validate the use of cluster analysis for characterizing population dietary patterns.

Design: Cluster analysis was applied to a food frequency questionnaire to define dietary patterns. Independent estimates of nutrient intake were derived from 3-day food records.

Induction of oxidative DNA damage in the peri-infarct region after permanent focal cerebral ischemia.

To address the role of oxidative DNA damage in focal cerebral ischemia lacking reperfusion, we investigated DNA base and strand damage in a rat model of permanent middle cerebral artery occlusion (MCAO). Contents of 8-hydroxyl-2'-deoxyguanosine (8-OHdG) and apurinic/apyrimidinic abasic sites (AP sites), hallmarks of oxidative DNA damage, were quantitatively measured in nuclear DNA extracts from brains obtained 4-72 h after MCAO. DNA single- and double-strand breaks were detected on coronal brain sections using in situ DNA polymerase I-mediated biotin-dATP nick-translation (PANT) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), respectively.

Characterization of the rat DNA fragmentation factor 35/Inhibitor of caspase-activated DNase (Short form). The endogenous inhibitor of caspase-dependent DNA fragmentation in neuronal apoptosis.

Nuclear changes, including internucleosomal DNA fragmentation, are classical manifestations of apoptosis for which the biochemical mechanisms have not been fully elucidated, particularly in neuronal cells. We have cloned the rat DNA fragmentation factor 35/inhibitor of caspase-activated DNase (short form) (DFF35/ICAD(S)) and found it to be the predominant form of ICAD present in rodent brain cells as well as in many other types of cells. DFF35/ICAD(S) forms a functional complex with DFF40/caspase-activated DNase (CAD) in the nucleus, and when its caspase-resistant mutant is over-expressed, it inhibits the nuclease activity, internucleosomal DNA fragmentation, and nuclear fragmentation but not the shrinkage and condensation of the nucleus, in neuron-differentiated PC12 cells in response to apoptosis inducers.