Die Entwicklungsgeschichte des Kopfskelettes des Cryptobranchus japonicus

Ohne ZusammenfassungMit 26 Textabbildungen.     

The effects of Na movement on surgical myocardial protection: the role of the Na+-H+ exchange system and Na-channel in the development of ischemia and reperfusion injury.

OBJECTIVES: We investigated whether the Na+-H+ exchange inhibitor, HOE642 (Hoe), and/or the Na channel blocker, mexiletine (Mex), enhance a cardioprotective effect on St. Thomas' Hospital cardioplegic solution (STS) to clarify the mechanism by which intracellular Na+ is accumulated after cardioplegic arrest. MATERIALS AND METHODS: Isolated working rat hearts were perfused with Krebs-Henseleit bicarbonate buffer (KHBB). The hearts were then arrested with STS and subjected to normothermic global ischemia (30 min). This was followed by Langendorff reperfusion (15 min) and then a working reperfusion (20 min). In study A, we added Hoe (5, 10, and 20 microM), Mex (70 microM), or a combination of Hoe (20 microM) and Mex (70 microM), to STS. In study B, we added Hoe (20 microM), Mex (70 microM), or a combination of Hoe (20 microM) and Mex (70 microM) to KHBB during the first 3 min of Langendorff reperfusion. RESULTS: In study A, the addition of Hoe (10 and 20 microM) to STS showed a significantly greater postischemic recovery of cardiac output compared to the control group [63.1+/-5.7% (10 microM), 62.7+/-4.7% (20 microM), and 55.5+/-4.6% (control), respectively]. The postischemic recovery of cardiac output was significantly greater in the group of the combined addition (Hoe and Mex) to STS than that in the control, 20 microM Hoe, 70 microM Mex groups [70.3+/-3.7 (Hoe and Mex), 55.5+/-4.6% (control), 62.7+/-4.7% (Hoe 20 microM), and 60.2+/-4.7% (Mex 70 microM), respectively]. The myocardial water content in the postischemic period was 565.1+/-29.1, 525.8+/-2.9, 509.4+/-19.6, and 532.2+/-20.1; it was 497.3+/-9.1 mL/100 g dry weight in the control; and 10 microM Hoe, 20 microM Hoe, and 70 microM Mex in the combined use groups. In study B, there was no significant difference in the postischemic recovery of cardiac output in all experimental groups. CONCLUSION: The combined use of the Na+-H+ exchange inhibitor and Na+ channel blocker during cardioplegia may achieve a superior cardioprotective effect on myocardial damage because of ischemia and reperfusion.     

Reduction of Nitric Oxide with L–/Vc–Monomethyl Arginine in lnterleukin–2 and Anti–CD3 Monoclonal Antibody Combination Therapy

We evaluated nitric oxide induction in antitumor therapy consisting of anti–CD3 monoclonal antibody (anti–CD3) and interleukin–2 (IL–2), then determined the effect of nitric oxide reduction with L–N^G–monomethyl arginine (LNMA) on the therapeutic methods. Female C57BL/6 mice, MCA102 (a non immunogenic, NK–resistant murine fibrosarcoma cell line), and 145–2C11 (hamster anti–murine–CD3 mAb) were utilized in an experimental hepatic metastasis model developed by injecting a tumor cell suspension into the spleen of mice. A marked increase in serum NO₂^–+ NO₁ was observed at 19 hours after anti–CD3 (10 μ, IV) and additional IL–2 administrations (40times10¹ U, twice, If) induced a further increase. The NO₂, + NO_3- elevation in spot urine in the combination therapy was not suppressed with LNMA at a dose of 100 μg/h but was significantly lowered at 300 μg/h. The efficacy of the anti–CD3 + IL–2 therapy was not diminished by LNMA administration either at 100 μg/h or at 300 μg/h.     

Research review: DNA polymerases as molecular markers of the regenerating capacity of hepatocytes

Hepatocyte regeneration has been widely investigated, with the mitotic index and the incorporation of [³H]thymidine being used as regeneration markers. We focused on the induction of DNA replication enzymes, particularly DNA polymerases (pol) α, δ, and ε. Using rat models, we have shown that the activity of pol α in crude liver extract well represents the regenerating capacity of hepatocytes. Using pol α as an indicator, we analyzed liver regeneration in rat models under various conditions: obstructive jaundice, external or internal biliary drainage, and the obstruction of portal vein branches. It has been revealed that the ligation of the common bile duct alone induces a certain amount of hepatocyte proliferation. It was striking that external biliary drainage suppressed regeneration capacity in cholestatic rat liver after partial hepatectomy. The strong regeneration in nonligated lobes induced by portal branch ligation was similar to the liver regeneration seen after partial hepatectomy with respect to the induction of DNA polymerases. Taken together, the aspects of DNA replication, particularly the induction of DNA polymerases, may contribute to shedding new light on the regeneration of human liver. This work was supported in part by a Grant-in-Aid for General Scientific Research and for Cancer Research from the Ministry of Education, Science and Culture, Japan, and by grants from the Uehara Memorial Foundation     

Expression of matrix metalloproteinase matrilysin (mmp-7) was induced by activated ki-ras via ap-1 activation in sw1417 colon cancer cells

The matrix metalloproteinase matrilysin (MMP-7) is a member of the matrix metallo-proteinase gene family, which is believed to play an important role in tumor invasion and metastasis. We have previously found that matrilysin mRNA is specifically expressed in colorectal cancers and adenomas and that its message is localized in the tumor cells themselves. We examined the effects of activated Ki-ras oncogene on the expression of matrilysin in colon cancer cells. We showed that both mRNA and the enzymatic activity of matrilysin were induced by the introduction of activated Ki-ras into SW1417 colon cancer cells. To understand the mechanisms regulating this induction, we analyzed alterations of AP-1 activity induced by activated Ki-ras, using the chloramphenicol acetyltransferase assay. AP-1 activity in SW1417 cells expressing activated Ki-ras was higher than that in control cells. The gel-shift assay also showed higher levels of AP-1 binding protein in SW1417 cells expressing activated Ki-ras than those in control cells. Our results suggest that activated Ki-ras may play a role in inducing expression of matrilysin through an AP-1-dependent pathway in colon cancer cells.     

Relation of inflammatory cytokines to atrial fibrillation after off-pump coronary artery bypass grafting.

OBJECTIVE: It has been observed that a systemic inflammatory response after on-pump coronary artery bypass grafting (CABG) participates in the pathogenesis of postoperative atrial fibrillation (AF). In patients undergoing off-pump CABG, it is plausible that inflammation is associated with the development of postoperative AF. The present study examined relation of proinflammatory cytokines, which play an important role in the upstream of inflammatory cascade, to the development of AF after off-pump CABG. METHODS: The present study included 39 patients undergoing off-pump CABG. Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8, were measured by enzyme-linked immunosorbent assay, on anesthetic induction, after sternotomy before anastomoses, at the completion of anastomoses, 3 and 6h thereafter, and on postoperative days (POD) 1-4. C-reactive protein (CRP) was also measured by turbidimetric immunoassay, preoperatively, and on POD 1, 2, 3, 6, 9, and 13. RESULTS: Eleven patients (28%) developed postoperative AF. Patients with postoperative AF were older (70+/-6.4 years vs 60+/-8.8 years, P=0.001); however, there was no difference in other pre- and perioperative variables. TNF-alpha level did not change during the study period. However, IL-8 and CRP levels significantly increased after the surgery, although there was no significant difference between the two groups. IL-6 level also increased after the surgery with its peak at 6h after the completion of anastomoses. IL-6 levels of 3 and 6h after anastomoses were significantly higher in patients with postoperative AF (360+/-143 pg/ml vs 230+/-94 pg/ml, P=0.0047, 435+/-175 pg/ml vs 247+/-102 pg/ml, P=0.0005, respectively). Logistic regression analysis indicated that the highest quartile of IL-6 level immediately after the surgery (odds ratio 7.63; 95% CI, 1.06-54.9; P=0.04) and age (odds ratio 1.18; 95% CI, 1.01-1.39; P=0.04) independently predict postoperative AF. Furthermore, the maximum level of IL-6 immediately after the surgery significantly correlated to age and intraoperative blood loss (r=0.04, P=0.01, and r=0.47, P=0.04, respectively). CONCLUSIONS: Advanced age was a major risk factor for postoperative AF. Furthermore, inflammatory response induced by surgical trauma was also associated with the development of AF after off-pump CABG.     

Prefrontal cerebral activity during a simple “rock, paper, scissors” task measured by the noninvasive near-infrared spectroscopy method

We conducted a noninvasive near-infrared spectroscopy (NIRS) study using the game of rock, paper, scissors (RPS) as a simple neurocognitive task for the prefrontal cortex (PFC) in 15 healthy volunteers. We employed an opposite “to lose” RPS task coupled with a normal “to win” RPS task, since the former requires inhibition of behavior, one of the most important functions of the prefrontal cortex. During the NIRS examination, subjects had to present one of the three RPS hands in response to hands displayed randomly on a computer screen every 1.5 s, and were required to show hands that lose to the computer, or that beat the computer. We measured the relative concentrations of oxyhemoglobin (oxy-Hb) using the prefrontal probes of the NIRS system during the tasks. The increases in oxy-Hb during the “to win” RPS task were small, but were quite large and laterally dominant during the “to lose” RPS task. The difference between the two tasks might have been due to the participants’ cognitive conflict with losing on the RPS. We conclude that losing is better than winning on the RPS as a sensitive indicator in the NIRS examination of PFC.     

Refractory hemolytic uremic syndrome improved by plasmapheresis using cryosupernatant fraction as a replacement fluid: A case report

A 52-year-old woman who had had 6 months of chemotherapy using mitomycin C and cisplatin for cervical cancer presented with hemolytic uremic syndrome. Conventional plasmapheresis using whole-plasma fraction was ineffective. However, plasmapheresis using the cryosupernatant fraction dramatically improved symptoms of hemolytic anemia and thrombocytopenia in this case. The activity of factor VIII in the cryosupernatant fraction of plasma as a replacement fluid decreased after removal of cryoprecipitate, indicating effective removal of von Willebrand factor. The pathogenesis of her hemolytic uremic syndrome may have been associated with von Willebrand factor multimers contained in the cryoprecipitate of plasma. Similar use of the cryosupernatant fraction of plasma could not be found in other reports of cases of hemolytic uremic syndrome. Plasmapheresis using the cryosupernatant fraction of plasma may improve refractory hemolytic uremic syndrome.