Factors associated with carotid atherosclerosis in community-dwelling oldest elderly aged over 80 years.

BACKGROUND: Hypertension, hyperlipidemia, impaired glucose tolerance and smoking have been known to be risk factors for atherosclerosis. Recently, it was shown that hyperhomocysteinemia is also a risk factor for cerebral vascular disease and atherosclerosis. However, it is unknown if these are also risk factors in the oldest elderly population aged 80 years or older. We carried out a cross-sectional analysis to determine the associated factors with carotid atherosclerosis in the oldest elderly living in the community. METHODS: Subjects consisted of 136 oldest elderly aged 80 years or older living in the community. Blood pressure, orthostatic change of blood pressure, blood chemical parameters, height and bodyweight, lifestyle and medical history were examined. The thickness was measured of the total carotid artery intima-media complex (IMT) by carotid artery ultrasonography and used the maximum thickness (max IMT) for analysis. RESULTS: The factors that correlated with max IMT were age and low gamma-glutamyl transpeptidase in males, and serum homocysteine levels in females. The subjects were divided into two groups: those with a max IMT of less than 1.0 mm and those with that of 1.0 mm or more. Factors associated with max IMT were age and abstinence from alcohol in males, and orthostatic blood pressure change in females. Factors significantly associated with higher carotid artery IMT were aging in males and orthostatic blood pressure change in females. CONCLUSION: The factors associated with carotid artery IMT as an indicator of carotid atherosclerosis in community-dwelling oldest elderly aged 80 years or older were sex, aging, orthostatic blood pressure change and no alcohol intake. There were differences in risk factors for carotid atherosclerosis between the male and female population.

High mobility group I-C protein in astrocytoma and glioblastoma.

High mobility group I-C (HMGI-C) protein is a non-histone DNA-binding factor that organizes active chromatin. This protein is expressed during the limited phase of embryonic development and may regulate the expression of genes critical for embryonic cell growth and differentiation. As embryonic mechanisms are also known to play a role in the development of some neoplasms, we investigated human brain tumors for the expression of HMGI-C to determine its role in the differentiation of glial cell tumors. Immunohistochemical analysis revealed HMGI-C in all of the low-grade astrocytomas, in 2 of 3 anaplastic astrocytomas (grade 3), but in only one of 8 glioblastomas. The results were confirmed at the mRNA level by nested reverse-transcription polymerase chain reaction analyses. Loss of HMGI-C was also demonstrated in a case of glioblastoma transformed from the low-grade astrocytoma strongly expressing HMGI-C protein. These results suggest that HMGI-C may be involved in the differentiation of glial tumor cells, and that loss of HMGI-C expression may contribute to the transformation of low-grade astrocytoma into glioblastoma.

Hepatitis C virus core protein interacts with p53-binding protein, 53BP2/Bbp/ASPP2, and inhibits p53-mediated apoptosis.

The core protein of Hepatitis C virus affects several biological functions of the host cells such as cellular growth and apoptosis. The core was shown to interact with 53BP2/Bbp/ASPP2, a p53-binding protein, in a yeast two-hybrid assay. The core competed with p53 in binding to ASPP2 in vitro. In an apoptosis assay using human osteosarcoma Saos-2 cells or hepatocellular carcinoma HepG2 cells, ectopic expression of p53 induced apoptosis and ASPP2 enhanced this p53-induced apoptosis. However, coexpression of the core with p53 and ASPP2 increased the number of surviving cells. In a reporter assay, neither ASPP2 nor the core with ASPP2 affected the transcriptional activity of p53 on the promoters of Bax and p21, major p53 target genes. These findings suggest that the core inhibits p53-mediated apoptosis by blocking the interaction between p53 and ASPP2, without modulating the transcriptional activity of p53, which plays a role in oncogenesis of hepatocellular carcinoma.

[Long-term effect of hypertension on neurobehavioral and cardiac function in the apparently healthy community-dwelling elderly: a 5-year follow-up study].

Recently, it has been reported that hypertension causes not only cerebro-cardiovascular diseases, but also a decline of cognitive function in the elderly. However, it is not clear whether or not aging and hypertension have a latent effect on the cognitive-neurobehavioral and cardiac functions in healthy elderly whose scores of basic activities of daily living (ADL) are fully maintained. We evaluated the effect of aging and hypertension on cognitive-neurobehavioral and cardiac functions in 25 healthy community-dwelling elderly subjects (mean age: 69 y.o.) whose scores of basic ADL were fully maintained. Subjects were followed over a 5-year period, and the following examinations were performed before and after a 5-year follow-up: echocardiography, 24-hr ambulatory blood pressure monitoring (ABPM), and cognitive-neurobehavioral function test. Left ventricular mass index was significantly increased in the hypertensive (HT) subjects relative to the normotensive (NT) subjects over the 5 years (% change: 3% for HT vs. -0.8% for NT, p = 0.03). The number of non-dippers significantly increased over the 5 years in the HT group (initially: 20% [2/10] vs. follow-up: 58% [7/12], p = 0.04). Visuospatial cognitive performance scale scores for evaluation of higher cognitive-neurobehavioral functions significantly deteriorated in the HT subjects (initially; 2,344 +/- 110 vs. 2,380 +/- 102, ns, and follow-up: 2,149 +/- 181 vs. 2,356 +/- 159, p = 0.04). Hypertension contributes to the impairment of the cognitive-neurobehavioral function in the elderly by latently affecting the functions of multiple organs. This occurs even if basic ADL is maintained for 5 years. Therefore, it is important to control BP not only to prevent cardiovascular events, but also to preserve the neurobehavioral function.

Potential role for 53BP1 in DNA end-joining repair through direct interaction with DNA.

Upon DNA damage, p53-binding protein 1 (53BP1) relocalizes to sites of DNA double-strand breaks and forms discrete nuclear foci, suggesting its role in DNA damage responses. We show that 53BP1 changed its localization from the detergent soluble to insoluble fraction after treatment of cells with x-ray, but not with ultraviolet or hydroxyurea. Either DNase or phosphatase treatment of the insoluble fraction released 53BP1 into the soluble fraction, showing that 53BP1 binds to chromatin in a phosphorylation-dependent manner after X-irradiation of cells. 53BP1 was retained at discrete nuclear foci in X-irradiated cells even after detergent extraction of cells, showing that the chromatin binding of 53BP1 occurs at sites of DNA double-strand breaks. The minimal domain for focus formation was identified by immunofluorescence staining of cells ectopically expressed with 53BP1 deletion mutants. This domain consisted of conserved Tudor and Myb motifs. The Tudor plus Myb domain possessed chromatin binding activity in vivo and bound directly to both double-stranded and single-stranded DNA in vitro. This domain also stimulated end-joining by DNA ligase IV/Xrcc4, but not by T4 DNA ligase in vitro. We conclude that 53BP1 has the potential to participate directly in the repair of DNA double-strand breaks.

Rhythm-independent feature of heart rate dynamics common to atrial fibrillation and sinus rhythm in patients with paroxysmal atrial fibrillation.

OBJECTIVES: To examine if the long-range correlation in heart rate variability is a rhythm-independent characteristic common to both atrial fibrillation (AF) and sinus rhythm (SR) periods in patients with paroxysmal atrial fibrillation (PAF). METHODS: Holter electrocardiography was analyzed during sleep in 18 patients with paroxysmal atrial fibrillation during the atrial fibrillation (PAF-AF) and sinus rhythm (PAF-SR) periods, and also in 19 healthy controls with sinus rhythm (CTR-SR). The heart rate dynamics were assessed with the power-law spectral exponent (slope) of the log-log power spectrum between 0.0001 Hz and the breakpoint frequency. RESULTS: The slope showed a significant correlation between PAF-SR and PAF-AF (r = 0.614, p < 0.01). During sinus rhythm, the slope in paroxysmal atrial fibrillation with cardiovascular disease [PAF-SR (cvd+)] was steeper than that in paroxysmal atrial fibrillation without cardiovascular disease [PAF-SR (cvd-)] (p < 0.05). Although the slope was comparable between PAF-SR (cvd-) and CTR-SR, the slope in PAF-SR (cvd+) was steeper than that in CTR-SR (p < 0.05). A similar tendency was shown during atrial fibrillation. The slope in paroxysmal atrial fibrillation with cardiovascular disease [PAF-AF (cvd+)] was steeper than that in paroxysmal atrial fibrillation without cardiovascular disease [PAF-AF (cvd-)] (p < 0.05). Although the slope was comparable between PAF-AF (cvd-) and CTR-SR, the slope in PAF-AF (cvd+) tended to be steeper than that in CTR-SR. CONCLUSIONS: The long-range correlation in heart rate variability during sleep was a rhythm-independent characteristic and so may have a similar clinical value during atrial fibrillation and sinus rhythm in patients with paroxysmal atrial fibrillation.