Using 6-Min Walk Distance Expressed as a Percentage of Reference to Evaluate the Effect of Pulmonary Rehabilitation in Elderly Patients With Interstitial Lung Disease.

PURPOSE: The aim of this study was to investigate the effect of outpatient pulmonary rehabilitation (PR) program and the use of 6-min walk distance (6MWD), expressed as a percentage of the predicted value (%6MWD), to quantify response to PR in elderly patients with interstitial lung disease (ILD). METHODS: This was a prospective, nonrandomized controlled study. Forty eligible patients with stable ILD (≥65 y old) were advised to attend an outpatient PR program for 3 mo. Thirteen patients completed the PR program and formed the PR group. Ten patients who did not attend the PR program were evaluated after 3 mo and formed the control group. Patients in the PR group underwent a comprehensive 3-mo hospital-based outpatient PR program, consisting of educational support and supervised exercise training, and attended the rehabilitation unit weekly. RESULTS: Change in the absolute 6MWD (Δ6MWD) in the PR group was not significantly different compared with the control group (P = .062). Change in %6MWD (Δ%6MWD) was greater in the PR group than in the control group. Baseline 6MWD was not correlated with Δ6MWD, but baseline %6MWD was significantly correlated with Δ6MWD and Δ%6MWD. CONCLUSION: PR had a beneficial effect on elderly patients with ILD in terms of exercise endurance. %6MWD might be more useful than the absolute 6MWD as an outcome measure of PR and as a predictor of response to PR in elderly patients with ILD.

A new disorder in UV-induced skin cancer with defective DNA repair distinct from xeroderma pigmentosum or Cockayne syndrome.

We report the characterization of a Japanese woman who exhibited many freckles and skin cancers in sun-exposed areas, but displayed no photosensitivity. Fibroblasts (KPSX7) derived from this patient showed similar UV sensitivity to that of normal human fibroblasts. The KPSX7 cells showed normal levels of unscheduled DNA synthesis, recovery of RNA synthesis, recovery of replicative DNA synthesis, protein-binding ability to UV-damaged DNA, and post-translational modification of xeroderma pigmentosum (XP) C. These results indicate that the patient had neither XP nor Cockayne syndrome. Although these results suggest that the KPSX7 cells were proficient in nucleotide excision repair activity, host-cell reactivation (HCR) activity of KPSX7 cells was reduced. Furthermore, introduction of UV damage endonuclease into the cells restored repair activity in the HCR assay to almost normal levels. These results indicate that KPSX7 cells are defective for some types of repair activity in UV-damaged DNA. In summary, the patient had a previously unknown disorder related to UV-induced carcinogenesis, with defective DNA repair.

Perturbed gap-filling synthesis in nucleotide excision repair causes histone H2AX phosphorylation in human quiescent cells.

Human histone H2AX is rapidly phosphorylated on serine 139 in response to DNA double-strand breaks and plays a crucial role in tethering the factors involved in DNA repair and damage signaling. Replication stress caused by hydroxyurea or UV also initiates H2AX phosphorylation in S-phase cells, although UV-induced H2AX phosphorylation in non-cycling cells has recently been observed. Here we study the UV-induced H2AX phosphorylation in human primary fibroblasts under growth-arrested conditions. This reaction absolutely depends on nucleotide excision repair (NER) and is mechanistically distinct from the replication stress-induced phosphorylation. The treatment of cytosine-beta-D-arabinofuranoside strikingly enhances the NER-dependent H2AX phosphorylation and induces the accumulation of replication protein A (RPA) and ATR-interacting protein (ATRIP) at locally UV-damaged subnuclear regions. Consistently, the phosphorylation appears to be mainly mediated by ataxia-telangiectasia mutated and Rad3-related (ATR), although Chk1 (Ser345) is not phosphorylated by the activated ATR. The cellular levels of DNA polymerases delta and epsilon and proliferating cell nuclear antigen are markedly reduced in quiescent cells. We propose a model that perturbed gap-filling synthesis following dual incision in NER generates single-strand DNA gaps and hence initiates H2AX phosphorylation by ATR with the aid of RPA and ATRIP.