Significance of Smoking as a Postoperative Prognostic Factor in Patients with Non-small Cell Lung Cancer

IntroductionIn this study, we investigated the influence of smoking on the postoperative prognosis in patients with non-small cell lung cancer.MethodsThe subjects consisted of 770 patients who underwent a resection of lung cancer in our department between 1994 and 2005. We compared the clinico-pathological findings between the smoking and never-smoking groups. The pack-year index (PYI) was used as a smoking index.ResultsThe smoking group consisted of 569 patients (74%), and the never-smoking group consisted of 201 patients (26%). The smokers were composed of 492 men and 77 women. Among the adenocarcinoma patients, there were 293 (61%) smokers and 185 (39%) never-smokers. The patients with squamous cell carcinoma included 204 (95%) smokers and 10 (5%) never-smokers. The proportion of patients with stage IA disease was significantly higher in the never-smokers than that of the smokers. The 5-year survival rate after surgery was 66% in the never-smoking group; however, the rates were 56% in patients with a PYI more than or equal to 20, and 55% in those with PYI more than 20. Seventy-nine (13.9%) patients in the smoking group and seven (3.5%) patients in the never-smoking group died of other diseases, with a significant difference (p < 0.01). Of these patients, 44 (56%) and 13 (16%) in the smoking group died of respiratory and cardiovascular disorders, respectively. In our series, excluding those who died of other diseases, there were no significant differences in the postoperative prognosis.ConclusionsIn the smoking group, the prognosis was poorer than that in the never-smoking group. The higher proportion of early stage disease (stage IA) and female gender were major causes of the better prognosis of the never-smokers. Nevertheless, the high pulmonary/cardiovascular complication-related mortality was another cause of the poor prognosis of the smokers with lung cancer

High Glucose Increases Metallothionein Expression in Renal Proximal Tubular Epithelial Cells

Metallothionein (MT) is an intracellular metal-binding, cysteine-rich protein, and is a potent antioxidant that protects cells and tissues from oxidative stress. Although the major isoforms MT-1 and -2 (MT-1/-2) are highly inducible in many tissues, the distribution and role of MT-1/-2 in diabetic nephropathy are poorly understood. In this study, diabetes was induced in adult male rats by streptozotocin, and renal tissues were stained with antibodies for MT-1/-2. MT-1/-2 expression was also evaluated in mProx24 cells, a mouse renal proximal tubular epithelial cell line, stimulated with high glucose medium and pretreated with the antioxidant vitamin E. MT-1/-2 expression was gradually and dramatically increased, mainly in the proximal tubular epithelial cells and to a lesser extent in the podocytes in diabetic rats, but was hardly observed in control rats. MT-1/-2 expression was also increased by high glucose stimulation in mProx24 cells. Because the induction of MT was suppressed by pretreatment with vitamin E, the expression of MT-1/-2 is induced, at least in part, by high glucose-induced oxidative stress. These observations suggest that MT-1/-2 is induced in renal proximal tubular epithelial cells as an antioxidant to protect the kidney from oxidative stress, and may offer a novel therapeutic target against diabetic nephropathy

Evidence-based bioethics: delineating the connections between science, practice, and values in medicine.

<p><b>A.</b> Secretion of FABP5 from adipose-derived stem cells (ADSC) after adipocyte differentiation at Day 0, Day 4 and Day 8 (n = 4 in each). Values were normalized to total protein concentration of the cell lysate. *P < 0.05 vs. Day 0. <b>B.</b> Flowchart of microarray analysis in ADSC treated with 1 μM recombinant FABP5 for 24 h. <b>C.</b> Gene ontology (GO) enrichment analysis. Significantly (Z-score > 0, P < 0.05) upregulated and downregulated GO terms of three GO categories, including cellular component, molecular function and biological process, were picked up and listed by a sort of lower P-value in each category. The abscissa of the bar plot was the number of annotated genes within the GO category. <b>D.</b> Cascade of the protein-protein interaction (PPI) network using a transcription factor binding site search data.</p

Identification of a novel biomarker candidate, a 4.8-kDa peptide fragment from a neurosecretory protein VGF precursor, by proteomic analysis of cerebrospinal fluid from children with acute encephalopathy using SELDI-TOF-MS

<p>Abstract</p> <p>Background</p> <p>Acute encephalopathy includes rapid deterioration and has a poor prognosis. Early intervention is essential to prevent progression of the disease and subsequent neurologic complications. However, in the acute period, true encephalopathy cannot easily be differentiated from febrile seizures, especially febrile seizures of the complex type. Thus, an early diagnostic marker has been sought in order to enable early intervention. The purpose of this study was to identify a novel marker candidate protein differentially expressed in the cerebrospinal fluid (CSF) of children with encephalopathy using proteomic analysis.</p> <p>Methods</p> <p>For detection of biomarkers, CSF samples were obtained from 13 children with acute encephalopathy and 42 children with febrile seizure. Mass spectral data were generated by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) technology, which is currently applied in many fields of biological and medical sciences. Diagnosis was made by at least two pediatric neurologists based on the clinical findings and routine examinations. All specimens were collected for diagnostic tests and the remaining portion of the specimens were used for the SELDI-TOF MS investigations.</p> <p>Results</p> <p>In experiment 1, CSF from patients with febrile seizures (n = 28), patients with encephalopathy (n = 8) (including influenza encephalopathy (n = 3), encephalopathy due to rotavirus (n = 1), human herpes virus 6 (n = 1)) were used for the SELDI analysis. In experiment 2, SELDI analysis was performed on CSF from a second set of febrile seizure patients (n = 14) and encephalopathy patients (n = 5). We found that the peak with an m/z of 4810 contributed the most to the separation of the two groups. After purification and identification of the 4.8-kDa protein, a 4.8-kDa proteolytic peptide fragment from the neurosecretory protein VGF precursor (VGF4.8) was identified as a novel biomarker for encephalopathy.</p> <p>Conclusions</p> <p>Expression of VGF4.8 has been reported to be decreased in pathologically degenerative changes such as Alzheimer's disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia, and encephalopathy. Thus, the VGF4.8 peptide might be a novel marker for degenerative brain conditions.</p

Urinary Level of Liver-Type Fatty Acid Binding Protein Reflects the Degree of Tubulointerstitial Damage in Polycystic Kidney Disease

Background/Aims: Polycystic kidney disease (PKD) is a common, progressive, and heritable type of kidney disease. Although certain imaging modalities are useful for the diagnosis and staging of PKD, they cannot adequately monitor the severity of interstitial inflammation and fibrosis. Therefore, the present study evaluated the urinary level of liver-type fatty acid binding protein (L-FABP) as a marker of interstitial inflammation and fibrosis in PKD. Methods: Male PCK/CrljCrl-Pkhd1pck/Crl (PCK) rats (n = 34) were used as an animal model of the PKD. Age-and sex-matched Sprague–Dawley rats (SD) (n = 34) were used as controls. Urine samples were obtained from the rats at 8, 12, 16, 20, and 24 weeks of age, and the sera and kidney tissues were obtained at 8, 16, 20, and 24 weeks of age. Results: All PCK rats developed cysts, and the degrees of tubular epithelial cell proliferation and interstitial inflammation increased linearly with age in these model rats relative to the controls. Interstitial fibrosis tended to increase in the PCK rats from 8 to 20 weeks of age, and revealed a peak level at 20 weeks. The urinary L-FABP levels increased linearly with age in the PCK rats, and the levels at 12, 16, 20, and 24 weeks were significantly higher than those in the controls. The urinary levels of L-FABP in the PCK rats correlated significantly with the severity of tubulointerstitial damage; specifically, we observed a significant correlation of the urinary levels at 16 weeks of age with the total kidney volume at 20 weeks. In contrast, both PCK and SD rats exhibited similar serum levels of L-FABP. Conclusion: Urinary L-FABP reflects the progression of tubulointerstitial damage, and therefore, may be a useful marker for monitoring the progression of PKD

Urinary liver-type fatty-acid binding protein is independently associated with graft failure in outpatient kidney transplant recipients

Urinary liver-type fatty acid-binding protein (uL-FABP) is a biomarker of kidney hypoxia and ischemia, and thus offers a novel approach to identify early kidney insults associated with increased risk of graft failure in outpatient kidney transplant recipients (KTR). We investigated whether uL-FABP is associated with graft failure and whether it improves risk prediction. We studied a cohort of 638 outpatient KTR with a functional graft ≥1-year. During a median follow-up of 5.3 years, 80 KTR developed graft failure. uL-FABP (median 2.11, interquartile range 0.93–7.37 µg/24"/>h) was prospectively associated with the risk of graft failure (hazard ratio 1.75; 95% confidence interval 1.27–2.41 per 1-SD increment; P =.001), independent of potential confounders including estimated glomerular filtration rate and proteinuria. uL-FABP showed excellent discrimination ability for graft failure (c-statistic of 0.83) and its addition to a prediction model composed by established clinical predictors of graft failure significantly improved the c-statistic to 0.89 (P for F-test <.001). These results were robust to several sensitivity analyses. Further validation studies are warranted to evaluate the potential use of a risk-prediction model including uL-FABP to improve identification of outpatient KTR at high risk of graft failure in clinical care

Paleoclimatic and paleoceanographic records through Marine Isotope Stage 19 at the Chiba composite section, central Japan: A key reference for the EarlyeMiddle Pleistocene Subseries boundary

Marine Isotope Stage (MIS) 19 is an important analogue for the present interglacial because of its similar orbital configuration, especially the phasing of the obliquity maximum to precession minimum. However, sedimentary records suitable for capturing both terrestrial and marine environmental changes are limited, and thus the climatic forcing mechanisms for MIS 19 are still largely unknown. The Chiba composite section, east-central Japanese archipelago, is a continuous and expanded marine sedimentary succession well suited to capture terrestrial and marine environmental changes through MIS 19. In this study, a detailed oxygen isotope chronology is established from late MIS 20 to early MIS 18, supported by a U-Pb zircon age and the presence of the Matuyama–Brunhes boundary. New pollen, marine microfossil, and planktonic foraminiferal δ18O and Mg/Ca paleotemperature records reveal the complex interplay of climatic influences. Our pollen data suggest that the duration of full interglacial conditions during MIS 19 extends from 785.0 to 775.1 ka (9.9 kyr), which offers an important natural baseline in predicting the duration of the present interglacial. A Younger Dryas-type cooling event is present during Termination IX, suggesting that such events are linked to this orbital configuration. Millennial- to multi-millennial-scale variations in our δ18O and Mg/Ca records imply that the Subarctic Front fluctuated in the northwestern Pacific Ocean during late MIS 19, probably in response to East Asian winter monsoon variability. The climatic setting at this time appears to be related to less severe summer insolation minima at 65˚N and/or high winter insolation at 50˚N. Our records do not support a recently hypothesized direct coupling between variations in the geomagnetic field intensity and global/regional climate change. Our highly resolved paleoclimatic and paleoceanographic records, coupled with a well-defined Matuyama–Brunhes boundary (772.9 ka; duration 1.9 kyr), establish the Chiba composite section as an exceptional climatic and chronological reference section for the Early–Middle Pleistocene boundary.ArticleQuaternary Science Reviews 191: 406-430(2018)journal articl