Interstrand DNA crosslinks (ICLs) are the link between Watson-Crick strands of DNAs with the covalent bond and prevent separation of DNA strands. Since the ICL lesion affects both strands of the DNA, the ICL repair is not simple. So far, nucleotide excision repair (NER), structure-specific endonucleases, translesion DNA synthesis (TLS), homologous recombination (HR), and factors responsible for Fanconi anemia (FA) are identified to be involved in ICL repair. Since the presence of ICL lesions causes severe defects in transcription and DNA replication, mutations in these DNA repair pathways give rise to a various hereditary disorders. NER plays an important role for the ICL recognition and removal in quiescent cells, and defects of NER causes congential progeria syndrome, such as xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. On the other hand, the ICL repair in S phase requires more complicated orchestration of multiple factors, including structure-specific endonucleases, and TLS, and HR. Disturbed this ICL repair orchestration in S phase causes genome instability resulting a cancer prone disease, Fanconi anemia. So far more than 30 factors in ICL repair have already identified. Recently, a new factor, UHRF1, was discovered as a sensor of ICLs. In addition to this, numbers of nucleases that are involved in the first incision, also called unhooking, of ICL lesions have also been identified. Here we summarize the recent studies of ICL associated disorders and repair mechanism, with emphasis in the first incision of ICLs.

Our results demonstrate that high glucose concentrations as well as high osmolarity inhibit FAK-mediated migration of mesothelial cells, and suggest that dialysates containing high glucose concentrations may cause peritoneal damage by inhibiting wound healing of the mesothelial cell monolayer.

Our results indicate that pressure per se can induce MCP-1 via activation of MAP kinase pathway, suggesting that glomerular hypertension might be involved in the progression of renal diseases through the expression of MCP-1 in MC.

Background: Plasma concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and cyclic guanosine monophosphate (cGMP) are suitable markers of ’dry body weight’ (DW) in hemodialysis (HD) patients. However, it is still unknown whether these markers can be applied to patients with renal failure and coronary artery disease (CAD). We examined the reliability of these peptides as volume markers in HD patients with CAD. We also assessed the relationship between natriuretic peptides and indices of left ventricular (LV) function. Methods: Plasma concentrations of ANP, BNP and cGMP were determined before and after HD in patients with CAD (group 1, n = 19, mean age 63 ± 12 years) and were compared with those of patients without cardiac disease (group 2, n = 20, age 61 ± 15 years). Using data obtained by cardiac catheterization, we examined the relationship between natriuretic peptides and indices of LV function in HD patients with CAD. Results: Baseline ANP (244 ± 205 pg/ml), BNP (713 ± 928 pg/ml) and cGMP (29.6 ± 21.6 pmol/ml) were significantly higher in group 1 than in 11 healthy volunteers (18.6 ± 9.9 pg/ml, 7.7 ± 7.6 pg/ml, cGMP 8.9 ± 4.9 pmol/ml, respectively). HD significantly reduced plasma ANP (87 ± 75 pg/ml) and BNP (477 ± 702 pg/ml) although they were still above normal control. HD reduced plasma cGMP (7.2 ± 4.5 pmol/ml) to normal values, suggesting the elimination of cGMP across the dialyzers. Baseline levels of ANP, BNP and cGMP in group 2 were less than those of group 1 but higher than the control. HD reduced natriuretic peptides in group 2 to levels lower than those in post-HD group 1. After HD, there was no significant correlation between reductions in body weight and changes in ANP or BNP. Baseline ANP and BNP levels closely correlated with pulmonary artery pressure, pulmonary artery wedge pressure, left ventricular end-diastolic pressure and left ventricular ejection fraction. A significant correlation was observed between BNP levels and the severity of CAD. Conclusion: ANP, BNP and cGMP seem to be a useful markers for fluid overload but not for DW in HD patients with CAD. Plasma ANP and BNP might be useful markers for left ventricular function.

We originated a novel control strategy for a continuous flow left ventricular assist device (LVAD). We examined our method by acute animal experiments to change the left ventricular (LV) contractility or LV end-diastolic pressure (LVEDP). To estimate the pump pulsatility without any specific sensor, we calculated the index of current amplitude (ICA) from motor current waveform. The ICA had a peak point (t-i point) that corresponded closely with the turning point from partial to total assistance, and a trough (s-i point) that corresponded with the beginning point of ventricular collapse. The pump flow at the t-i point (Qt-i) had no component of flow regurgitation. In the evaluation of the effects of preload LVEDP, afterload (mAoP), and contractility (max LV dp/dt), we found that preload was the only parameter that significantly influenced Qt-i. We concluded that our method could well control continuous flow LVAD by preventing reversed flow and ventricular collapse.