A significant imbalance in mitosis versus apoptosis accelerates the growth rate of sessile serrated adenoma/polyps

Sessile serrated adenoma/polyps (SSA/Ps) of the colon are thought to be precursors of sporadic carcinomas. Although it is suggested that SSA/P may grow rapidly from the early stage, its cell kinetics remains obscure. To solve this problem, we analyzed the mitotic and apoptotic activity of normal crypts, microvesicular hyperplastic polyps (MVHPs), and tubular adenomas (TAs), using phospho-histone H3 and cleaved caspase 3 immunohistochemistry. The mitotic index for SSA/Ps (mean, 5.63) and TAs (6.98) was significantly higher than those for normal crypts (2.72) and MVHPs (2.86). Of all tested lesions, the apoptotic index was lowest for SSA/Ps (0.96; normal, 2.71; MVHPs, 2.62; TAs, 6.01) with statistically significant differences. The net growth ratio was close to 1.0 in normal crypts (1.07) while remaining low in MVHPs (1.06) and TAs (1.38), but was markedly elevated in SSA/Ps (7.32, P?<?0.01) due to the large imbalance between mitosis and apoptosis. As to apoptosis regulatory proteins, expression of anti-apoptotic Bcl-2 was significantly reduced or undetectable in MVHPs and SSA/Ps, while TAs showed stronger staining than normal crypts. Expression of pro-apoptotic Bax and its activators, Bim and Bad, was significantly reduced in MVHPs and SSA/Ps. We suggest that other complex mechanisms may act synergistically with Bax, Bim, or Bad deficiency to regulate apoptosis suppression in SSA/Ps.     

Studies on insulin-like growth factors (IGF-I, -II) and there binding proteins in normal human pregnancy

In order to elucidate the roles of Insulin-like Growth Factors (IGF-I, -II) in human pregnancy, the levels of IGF-I and IGF-II, the distribution of binding proteins for IGF-I or IGF-II and profiles of unsaturated somatomedin binding proteins (USBP) were estimated in maternal and cord plasma. IGF-I levels in maternal plasma gradually elevated in late gestation, reaching 304.4 +/- 130.1ng/ml at term, and were significantly higher than those in nonpregnant women (188 +/- 58). IGF-II levels, which were 414.9 +/- 75.4ng/ml in women in the third trimester of gestation, did not produce any remarkable changes in the levels in nonpregnant women (395.9 +/- 72.6). On the other hand, IGF-I in cord plasma also increased according to gestational age, reaching 37.3 +/- 14.6ng/ml at term, but it was significantly lower than that in maternal weight (r = 0.50, p less than 0.005) and relative birth weight (r = 0.41, p less than 0.005). IGF-II in cord plasma showed no significant changes during gestation, however, IGF-II levels in AFD (appropriate for date) newborns delivered at term (203.8 +/- 59.4) were significantly lower than those in maternal plasma. And they had no positive correlations with birth weight and relative birth weight. On Sephadex G150 gel-chromatography of cord plasma from AFD newborns at term, more than 70% of immunoreactive IGF-I in plasma was eluted at 150K region, and 150K USBP could be detected as observed in adult plasma. On the other hand, most of the immunoreactive IGF-II was eluted at 40K region, and 150K USBP was not detected in AFD newborns at term. In adult plasma, most of the immunoreactive IGF-II was eluted at 150K region, but 150K USBP could not be detected. From these results, it is supposed that IGF-I plays an essential role in fetal growth rather than IGF-II.     

Subclinical Hypothyroidism Is Associated With Adverse Prognosis in Heart Failure Patients

Background

It is widely recognized that overt hyper- as well as hypothyroidism are potential causes of heart failure (HF). Additionally it has been recently reported that subclinical hypothyroidism (sub-hypo) is associated with atherosclerosis, development of HF, and cardiovascular death. We aimed to clarify the effect of sub-hypo on prognosis of HF, and underlying hemodynamics and exercise capacity.

Identification of Candidate Long Noncoding RNAs Associated with Left Ventricular Hypertrophy

Purpose

Long noncoding RNAs (lncRNAs) constitute an emerging group of noncoding RNAs, which regulate gene expression. Their role in cardiac disease is poorly known. Here, we investigated the association between lncRNAs and left ventricular hypertrophy.

Methods

Wild‐type and adenosine A2A receptor overexpressing mice (A2A‐Tg) were subjected to transverse aortic constriction (TAC) and expression of lncRNAs in the heart was investigated using genome‐wide microarrays and an analytical pipeline specifically developed for lncRNAs.

Results

Microarray analysis identified two lncRNAs up‐regulated and three down‐regulated in the hearts of A2A‐Tg mice subjected to TAC. Quantitative PCR showed that lncRNAs 2900055J20Rik and Gm14005 were decreased in A2A‐Tg mice (3.5‐ and 1.8‐fold, p < 0.01). We found from public microarray dataset that 2900055J20Rik and Gm14005 were increased in TAC mice compared to sham‐operated animals (1.8‐ and 1.4‐fold, after 28 days, p < 0.01). Interestingly, in this public dataset, cardioprotective drug JQ1 decreased 2900055J20Rik and Gm14005 expression by 2.2‐ and 1.6‐fold (p < 0.01).

Conclusions

First, we have shown that data on lncRNAs can be obtained from gene expression microarrays. Second, expression of lncRNAs 2900055J20Rik and Gm14005 is regulated after TAC and can be modulated by cardioprotective molecules. These observations motivate further investigation of the therapeutic value of lncRNAs in the heart.     

Craniofacial anatomical risk factors in men with obstructive sleep apnea and heart failure: a pilot study

Purpose

Obstructive sleep apnea (OSA) is complicated with heart failure (HF); however, the reason for this is not well understood. Craniofacial anatomic risk factors may contribute to OSA pathogenesis in HF patients. However, there are no data about cephalometric findings among OSA patients with HF.

Methods

Consecutive patients with HF and OSA (defined as total apnea–hypopnea index (AHI) ≥15/h) were enrolled. As controls, OSA patients without HF but matching the test group in age, BMI, and obstructive AHI were also enrolled.

Results

Overall, 17 OSA patients with HF and 34 OSA patients without HF were compared. There are no significant differences in the characteristics or polysomnographic parameters between 2 groups. In the cephalometric findings, compared with patients without HF, patients with HF showed a significantly greater angle between the line SN to point “A” (SNA) and a longer inferior airway space and greater airway area. However, the tongue area of patients with HF was more than those without HF.

Conclusions

The craniofacial structures of OSA patients with HF were different from those without HF. OSA patients with HF had an upper airway anatomy that is more likely to collapse when sleeping while recumbent, despite having a larger airway space.