Clinical and molecular epidemiological features of tuberculosis after the 2011 Japan earthquake and tsunami.

OBJECTIVE: To investigate clinical characteristics and prognosis in tuberculosis (TB) patients and the transmission dynamics of TB after the 2011 Japan earthquake and tsunami. METHOD: This was a retrospective observational cohort study. Data were analyzed among 93 pulmonary TB patients (tsunami-affected areas 25, non-tsunami areas 68) hospitalized during March 2011-March 2012 with 1-year follow-up since treatment commencement. Variable number of tandem repeats (VNTR) typing was conducted for 38 TB strains (tsunami-affected areas 21, non-tsunami areas 17). RESULTS: Patients from tsunami-affected areas were significantly more likely to be refugees (OR 12.8, 95%CI 2.45-67.20), receive oxygenation (OR 5.0, 95%CI 1.68-14.85), and have a unique VNTR (OR 4.6, 95%CI 1.14-18.41). Patients who died within 1 year were significantly more likely to be older (OR 9.8, 95%CI 1.85-180.26), partially dependent or dependent (OR 11.9, 95%CI 4.28-37.62), and to require oxygenation (OR 4.3, 95%CI 1.47-12.89), and had lower serum albumin levels (OR 11.1, 95%CI 2.97-72.32). CONCLUSION: Risk factors for prognosis of TB after the earthquake were associated with advanced age, low serum albumin level, functional status at admission, and oxygen requirement. The VNTR results suggest that most of the cases with pulmonary TB experienced reactivation of latent tuberculous infection, likely due to the impact of the earthquake and tsunami.

Prognostic value of nucleolar protein p120 in patients with resected lung adenocarcinoma.

PURPOSE: In this study we investigated the prognostic significance of proliferation-associated nucleolar protein p120 in primary resected lung adenocarcinoma because it reflects tumor growth fractions in vitro. PATIENTS AND METHODS: Expression levels of p120 in tumors were assessed by immunohistochemistry in 74 patients who underwent radical resection. With clinical follow-up data, the prognostic significance of p120 calculated by labeling indices was evaluated using the Cox proportional hazards model. RESULTS: p120 protein was clearly detected in nucleoli of adenocarcinoma cells. Its expression levels widely varied in each sample from 8.5% to 67. 2%, with a mean +/- SD of 35.2% +/- 15.1%. No significant correlation was found between expression levels of p120 and clinicopathologic factors. However, the expression levels of p120 were negatively correlated with the tumor doubling time calculated with retrospective chest roentgenograms. Using a cutoff value of 35% in the labeling index of p120, patients with high expression of p120 experienced early recurrence and shorter survival compared with those who had low expression of p120. Multivariate analysis showed that p120 served as an independent, as well as the strongest, prognostic factor for resected lung adenocarcinoma. CONCLUSION: This report provides the first evidence that expression levels of p120 in tumor tissues can be used as an independent and powerful prognostic marker for resected lung adenocarcinoma.

[Gamma-knife radiosurgery for metastatic brain tumors from primary lung cancer].

Forty patients with metastatic brain tumors from primary lung cancer underwent radiosurgery (gamma-knife). We retrospectively compared their prior treatment history number of metastatic foci, and performance status, to evaluate the effects of, and indications for, gamma-knife therapy. After both the primary and the metastatic tumors were controlled, performance status could be used as an index in the choice of gamma-knife therapy. Our results demonstrate that repeated gamma-knife radiosurgeries prolonged survival time. Gamma-knife radiosurgery improves quality of life and prognosis of patients with metastatic brain tumors.

Contiguous four-guanosine sequence in c-myc antisense phosphorothioate oligonucleotides inhibits cell growth on human lung cancer cells: possible involvement of cell adhesion inhibition.

A contiguous four-guanosine (4G) sequence in c-myc antisense phosphorothioate oligonucleotides caused an antiproliferative effect in smooth muscle cells. To investigate the antiproliferative effect of c-myc antisense oligonucleotides on human lung cancer cell lines, we synthesized oligonucleotides of various lengths and sequences, focusing on the contiguous four-guanosine (4G) sequence. While a c-myc antisense oligonucleotide (20AS1 (4G)) targeted to the translation initiation codon of c-myc mRNA inhibited cell growth of A549 cells by 69% at 10 microM, a scrambled oligonucleotide (20SCR1 (4G)) containing the contiguous four-guanosine (4G) sequence also inhibited cell growth by 72% at the same dose. Although treatment with either 20AS1 (4G) or 20SCR1 (4G) inhibited cell adhesion by 70% at 10 microM, expression of c-myc protein was significantly suppressed only by 20AS1 (4G) (62%), and was only weakly inhibited by 20SCR1 (4G) (32%). Furthermore, a small cell lung carcinoma cell line, Lu65, which can grow in suspension form, was highly resistant to 20AS1 (4G) treatment (IC50>20 microM). These results suggest that the cell growth inhibition by c-myc antisense oligonucleotides containing the contiguous four-guanosine (4G) sequence was possibly correlated with inhibition of cell adhesion, but not with inhibition of c-myc protein expression, via a sequence-specific non-antisense mechanism.

Expression of nucleolar protein p120 in human lung cancer: difference in histological types as a marker for proliferation.

The function of proliferation-associated nucleolar protein p120 is unclear. A recent report that a yeast protein, NOP2, 67% homologous to human p120, is up-regulated during the onset of growth and influences the morphology of the nucleolus supports the notion that this protein could serve as a marker for proliferation in neoplastic cells. Lung cancer is characteristic in that different histological types show different biological features. We attempted to evaluate the levels of p120 expression in resected human lung cancer tissues of different histological types and the relation of p120 expression and cell proliferation using human lung cancer cell lines. When 37 frozen specimens of human lung cancer and normal lung were stained with a p120 monoclonal antibody, the nucleoli of cancer cells were positively stained, whereas a few macrophages in normal lung revealed only weak staining. The labeling index of p120 in squamous cell carcinoma (67.7 +/- 12.4%) was significantly higher than that in adenocarcinoma (35.3 +/- 12.6%) or in large cell carcinoma (30.1 +/- 17.3%; P < 0.01). In six human lung cancer cell lines and one normal lung fibroblast cell line cultured in vitro, there was a significant correlation between S-phase fraction and p120 mRNA (r = 0.851, P < 0.02)/p120 protein (r = 0.869, P < 0.01) or between doubling time and p120 protein (r = -0.928, P < 0.01). In the context of the reports that indicate higher [3H]thymidine incorporation and shorter doubling time in the squamous cell carcinoma, these results indicate that p120 can be a marker for proliferation in human lung cancer cells in vivo and in vitro, and that it has an important function in the cell cycle of tumor proliferation.

[New strategies for the etiologic study of interstitial pneumonia: familial registration and sib-pair analysis].

Etiology of idiopathic interstitial pneumonia (IIP) remains unknown. While many studies focused on the analysis of individual patients, available information is limited for the further study. Having experienced a case, 3 of 5 brothers suffered from IIP and 2 of them complicated with lung cancer, intensive familial history taking with chest photos and functional information for fibrotic lung was performed. Among 37 families in which at least 2 members were examined, 14 families (37.8%) had minimum 2 members with fibrotic lungs. Unexpectedly high familial accumulation of fibrotic lung indicates the possibility of multi-gene involvement for the pathogenesis. We need to start group studies to register sib-pairs with fibrotic lungs and systematize the automated genetic analysis for the responsible genes.