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

GW501516, a PPARδ Agonist, Ameliorates Tubulointerstitial Inflammation in Proteinuric Kidney Disease via Inhibition of TAK1-NFκB Pathway in Mice

Peroxisome proliferator-activated receptors (PPARs) are a nuclear receptor family of ligand-inducible transcription factors, which have three different isoforms: PPARα, δ and γ. It has been demonstrated that PPARα and γ agonists have renoprotective effects in proteinuric kidney diseases; however, the role of PPARδ agonists in kidney diseases remains unclear. Thus, we examined the renoprotective effect of GW501516, a PPARδ agonist, in a protein-overload mouse nephropathy model and identified its molecular mechanism. Mice fed with a control diet or GW501516-containing diet were intraperitoneally injected with free fatty acid (FFA)-bound albumin or PBS(−). In the control group, protein overload caused tubular damages, macrophage infiltration and increased mRNA expression of MCP-1 and TNFα. These effects were prevented by GW501516 treatment. In proteinuric kidney diseases, excess exposure of proximal tubular cells to albumin, FFA bound to albumin or cytokines such as TNFα is detrimental. In vitro studies using cultured proximal tubular cells showed that GW501516 attenuated both TNFα- and FFA (palmitate)-induced, but not albumin-induced, MCP-1 expression via direct inhibition of the TGF-β activated kinase 1 (TAK1)-NFκB pathway, a common downstream signaling pathway to TNFα receptor and toll-like receptor-4. In conclusion, we demonstrate that GW501516 has an anti-inflammatory effect in renal tubular cells and may serve as a therapeutic candidate to attenuate tubulointerstitial lesions in proteinuric kidney diseases

アクアビルナウイルスによるVNN抵抗性の誘導

非病原性アクアビルナウイルス(ABV)を予め接種され、その 7 日後にベータノダウイルス(NNV)で攻撃されたマハタは NNV 感染に対して強い抵抗性を示した。他方、ヒラメではNNVに対する感受性が低いため死亡率からABVの効果をみることはできなかったが、脳および腎臓におけるNNVの消長をみると、両魚種とも ABV 処理魚において明らかにウイルス感染力価の低下が認められた。この防御は、ABVにより誘導されるインターフェロン関連タンパク質に因ると考えられた。Experimental dual-infections with a non-lethal aquabirnavirus (ABV) and a lethal betanodavirus (redspotted grouper nervous necrosis virus: RGNNV) were carried out in Japanese flounder Paralichthys olivaceus and sevenband grouper Epinephelus septemfasciatus. In the dual-infection group, ABV was intramuscularly (IM) injected into fish seven days before the IM-injection with RGNNV. In the experiments with flounder, a high expression of an Mx gene, a molecular marker for type I interferon(s) (IFM) production, occurred in the head kidneys and brains at Day 7 post-ABV injection. Although-no mortality was found not only in the dual-infected group but also in the single infection group with RGNNV (control group), the infective titers of RGNNV in the tissues of the dual-infected group were significantly lower at any sampling times than those in the control group. In the experiments with grouper, the preceding ABV infection resulted in complete protection against RGNNV infection. The infective titers of RGNNV in the tissues were also lower in the dual-infected group than in the control group throughout the experiments, and finally the virus disappeared from the head kidneys and brains of the dual-infected group at Day 14 and Day 56 postinjections, respectively. These results suggest that an ABV-induced IFN(s) effectively suppresses the progression of secondary betanodavirus infection

Therapeutic efficacy of an elemental diet for patients with crohn's disease and its association with amino acid metabolism

Background/Aim: We investigated the association between blood amino acid concentration changes caused by elemental diet (ED) and their relationship to its therapeutic effect. Patients and Methods: Patients with active Crohn's disease (CD) followed ED for 12 weeks. Patients not previously treated with ED were defined as new ED, and those with previous ED therapy (≥900 kcal/day) were defined as previous ED. Disease activity markers [Crohn's disease activity index (CDAI) and C-reactive protein (CRP) level], blood biochemistry test results, and plasma amino acid concentrations were measured before and after the treatment. Results: Histidine (His), tryptophan (Trp), valine (Val), and methionine (Met) increased after the treatment in the 17 patients with clinical remission, however, no increase occurred in plasma amino acid concentrations in the 8 patients without remission. The multivariate index using AminoIndex™technology (MIAI) was correlated with the CDAI (r = 0.475,P < 0.001), and it decreased as patients' conditions improved during the treatment. All patients in the new ED group (n = 11) exhibited increases in the nutritional indices, albumin level, and body mass index after treatment, as well as increased levels of His, Trp, Val, and phenylalanine. None of these changes were observed in the previous ED group (n = 14). Conclusions: Plasma amino acid concentrations and MIAI may provide useful noninvasive markers for evaluating disease activity and response to treatment. ED was effective in improving disease activity, nutritional status, and plasma amino acid levels, and thus it may be particularly effective for poorly nourished patients with CD who have not previously undergone this treatment

The variable region of RNA2 is sufficient to determine host specificity in betanodaviruses.

Betanodaviruses, the causative agents of viral nervous necrosis in marine fish, have bipartite positive-sense RNA genomes. The viruses have been classified into 4 distinct types based on nucleotide sequence similarities in the variable region (the so-called T4 region) of the smaller genomic segment RNA2 (1.4 kb). Betanodaviruses have marked host specificity, although the primary structures of the viral RNAs and encoded proteins are similar among the viruses. We have previously demonstrated, using reassortants between striped jack nervous necrosis virus (SJNNV) and redspotted grouper nervous necrosis virus (RGNNV), that RNA2, which encodes the coat protein, strictly controls host specificity. However, because RNA2 is large, we were unable to propose a mechanism underlying this RNA2-based host specificity. To identify the RNA2 region that controls host specificity, we constructed RNA2 chimeric viruses from SJNNV and RGNNV and tested their infectivity in the original host fish, striped jack Pseudocaranx dentex and sevenband grouper Epinephelus septemfasciatus. Among these chimeric viruses, SJNNV mutants containing the variable region of RGNNV RNA2 infected sevenband grouper larvae in a manner similar to RGNNV, while RGNNV mutants containing the variable region of SJNNV RNA2 infected striped jack larvae in a manner similar to SJNNV. Immunofluorescence microscopic studies using anti-SJNNV polyclonal antibodies revealed that these chimeric viruses multiplied in the brains, spinal cords and retinas of the infected fish, as in infections by the parental viruses. These results indicate that the variable region of RNA2 is sufficient to control host specificity in SJNNV and RGNNV

Clinicopathological Characteristics of Invasive Lobular Carcinoma of the Breast

The clinical features of invasive lobular carcinoma (ILC) of the breast have remained unclear due to the rarity of such cases. This study investigated the clinical and pathological features of ILC. Methods: The medical records of 413 patients with invasive breast cancer who underwent surgery in our department were reviewed. These cases included 13 patients with ILC (3.1%). Results: The age of the patients ranged from 36 to 77 years old (mean, 56). The tumour size was evaluated as T1 in five patients, T2–4 in 8. The lymph node metastasis was diagnosed as negative in six patients, positive in six. In this patient population, 11 (85%) and nine (69%) patients were positive for oestrogen and progesterone receptors, respectively. The 5-year survival rate was 76.2%, which was not significantly different from other types of invasive breast cancer. Extensive intraperitoneal metastasis was observed in two of the three patients. Two patients had bilateral carcinoma and one patient had a multicentric lesion in the ipsilateral breast. Conclusion: Multicentric development of breast cancer and intraperitoneal metastasis were one of clinical characteristics of ILC. The prognosis of ILC was not significantly different from other types of invasive breast carcinoma