Bikunin suppresses lipopolysaccharide-induced lethality through down-regulation of tumor necrosis factor- alpha and interleukin-1 beta in macrophages

BACKGROUND: Lipopolysaccharide (LPS) is the primary mediator of gram-negative sepsis; it induces the production of macrophage-derived cytokines. It has been shown that bikunin, a Kunitz-type protease inhibitor, inhibits LPS-induced cytokine expression. METHODS: To explore the role of bikunin, bikunin knockout (Bik(-/-)) mice were used for in vitro cytokine experiments and in vivo animal models. RESULTS: We show that a higher level of LPS-mediated death was induced in Bik(-/-), compared with wild-type (wt), mice; the administration of bikunin caused a significant reduction in LPS-induced lethality; LPS significantly increased tumor necrosis factor (TNF)- alpha and interleukin-1 beta levels in Bik(-/-), relative to wt, mice after LPS challenge; concomitant administration of bikunin inhibited the LPS-induced plasma levels of these cytokines; bikunin suppressed the LPS-induced up-regulation of cytokine expression through the suppression of the phosphorylation of ERK1/2, JNK, and p38 in macrophages; and LPS-induced up-regulation of TNF- alpha expression was not enhanced in Bik(-/-) macrophages without endogenous bikunin. CONCLUSIONS: These data allow us to speculate that the increased sensitivity of Bik(-/-) mice to LPS-induced death in vivo is due to a lack of circulating bikunin in plasma. Bikunin may play a role as a potent anti-inflammatory agent.     

Thoracoscopic rib resection and reconstruction of chest wall: Our clinical experience

Chest wall resection is traditionally performed via open thoracotomy, a procedure that increases surgical morbidity and reduces postoperative quality of life. Conversely, thoracoscopic chest wall resection may minimize invasiveness but the optimal procedure remains uncertain. We previously reported rib resection using a pneumatic high‐speed power drill during video‐assisted thoracoscopic surgery for selected lung cancer patients. In this report, we present two cases of chest wall tumor resected using the drill via the thoracoscopic approach. We also report thoracoscopic chest wall reconstruction in one patient using a patch sheet.     

Clinical manifestations in patients with hereditary nonpolyposis colorectal cancer

The clinical manifestations of 1,042 Japanese patients with nonpolyposis colorectal cancer who underwent a resection between 1972 and 1992 at the National Kyushu Cancer Center were examined. Hereditary nonpolyposis colorectal cancer (HNPCC) was found in 39 (3.7%) patients. Some characteristic findings in HNPCC cases included early age of onset, a preponderance of right colon cancers, an increased frequency of colorectal cancers, and a favorable survival. Metachronous (postoperative) colorectal cancers developed significantly more often in cases with HNPCC than in those without (12.8% vs. 1.8%, P = 0.0001). Metachronous (postoperative) extracolonic cancers tended to develop more often in cases with HNPCC than in those without (10.2% vs. 3.5%, P = 0.053). In cases with HNPCC, the mean interval between the initial surgery and the diagnosis of the second cancer was 61 months (range; 12–153 months). These findings thus indicate the importance of routine and long-term follow-up to identify any second lesions, especially in patients with HNPCC. © 1996 Wiley-Liss, Inc.     

Establishment and characterization of two cultured cell lines derived from malignant rhabdoid tumors of the kidney

Malignant rhabdoid tumor of the kidney (RTK) is a rare renal sarcoma of childhood. Its histogenesis is unclear, and it is highly resistant to multimodality therapy. To elucidate the origin and the oncogenetic potential of RTK, we investigated the characteristics of 2 newly established RTK cell lines, SWT-1 and SWT-2. Both cell lines were verified to be RTK, since they did not exhibit contact inhibition and exhibited intermediate filaments, a specific marker for RTK. These cells possess the characteristics of mesenchymal cells based on their positive reactions with anti-vimentin and anti-laminin antibodies and their negative reactions with anti-keratin and anti-desmin antibodies. The karyotype of SWT-1 was 46,XX and that of SWT-2 was 46,XX,del(II)(pter-p13::p12-qter). Since 11p13 is the location of the WT-1 tumor-suppressor gene, and del(11p13) is associated with the aniridia-Wilms'-tumor syndrome, these findings link RTK with Wilms' tumor. While SWT-1 was negative for the tumor markers examined, SWT-2 released tissue polypeptide antigen into the culture supernatant. No rearrangement or amplification of the myc and ras oncogenes or of the p53 tumor-suppressor gene were detected. Wild-type RB protein and cyclin A were expressed in both cells. Our data suggest that these 2 cell lines may be useful in identifying the oncogenetic pattern of RTK. © 1996 Wiley-Liss, Inc.     

Comparison of patency of single and sequential radial artery grafting in coronary artery bypass

Open in a separate window OBJECTIVESSequential radial artery (RA) grafting has the potential to enhance arterial revascularization compared to single grafting. Sequential RA grafting was performed predominantly with a single side-to-side anastomosis. The study aimed to assess if sequential RA grafting improved long-term graft patency compared to single RA grafting. In addition, the anastomotic patencies of side-to-side and end-to-side anastomoses in sequential RA grafting were assessed.METHODSTwo hundred nineteen patients underwent isolated coronary artery bypass grafting with skeletonized RA conduits between 2005 and 2016. Of these, 208 patients underwent radiological graft assessment; thus, 125 and 83 patients underwent single and sequential RA grafting, respectively. The graft and anastomotic patency rates were estimated using the Kaplan–Meier method.RESULTSThe median follow-up period was 9.1 years, and the radiological assessment lasted 5.1 years. The overall RA graft patency rates at 1, 5 and 10 years were 99.4%, 92.7% and 88.1%, respectively. The RA graft patency rate for sequential grafting was similar to that for single grafting (88.7% vs 87.4% at 10 years; P = 0.88). In the stratified analysis of anastomotic patency, the patency rate of side-to-side anastomoses of sequential RA grafting was significantly better than that of end-to-side anastomoses (100% vs 88.7% at 10 years; P = 0.01).CONCLUSIONSThe long-term RA graft patencies of sequential and single grafting were equally high. The anastomotic patency of side-to-side anastomoses of sequential RA grafting was remarkably high. Considering these findings, the RA can be effectively used for multiple arterial coronary revascularizations.     

Prefrontal cortex and amygdala volume in first minor or major depressive episode after cancer diagnosis.

BACKGROUND: Major and minor depressive episodes in cancer patients are frequent and are frequently seen as the first depressive episode in a patient's life. However, the neurological basis of these depressive episodes remains largely unknown. METHODS: Subjects were 51 breast cancer survivors (BCS) who had no history of any depressive episode before the cancer diagnosis (11 BCS with a history of a first minor depressive episode after cancer diagnosis, 11 BCS with a history of a first major depressive episode after cancer diagnosis, and 29 BCS with no history of any depressive episode after cancer diagnosis). We analyzed the prefrontal cortex (PFC) and amygdala volumes in a 1.5-Tesla Magnetic Resonance Imaging scanner. We characterized the structural correlates of depression using two complementary approaches. The first was voxel-based morphometry (VBM) that allowed us to scan the entire brain for reactive gray matter deficit. The second was classical volumetry focusing on the amygdala. RESULTS: Voxel-based morphometry revealed no brain region, including PFC, for which volume was significantly different among the three groups. There were trend-level differences in the left amygdala volume in the manual tracing method among the three groups. The left amygdala volumes in the subjects with a first minor and/or major depressive episode were significantly smaller than in those with no history of any depressive episode. CONCLUSIONS: It might be suggested that amygdala volume was associated with a first minor and/or major depressive episode after cancer diagnosis.