Organophosphorus pesticides (OPs) are widely used throughout the world as insecticides in agriculture and as eradicating agents for termites around homes. The main toxicity of OPs is neurotoxicity, which is caused by the inhibition of acetylcholinesterase. OPs also affect the immune response, including effects on antibody production, interleukin-2 production, T cell proliferation, decrease of CD5 cells, and increases of CD26 cells and autoantibodies, Th1/Th2 cytokine profiles, and the inhibition of natural killer (NK) cell, lymphokine-activated killer (LAK) cell, and cytotoxic T lymphocyte (CTL) activities. However, there have been few studies of the mechanism of OP-induced immunotoxicity, especially the mechanism of OP-induced inhibition of cytolytic activity of killer cells. This study reviews new mechanisms of OP-induced inhibition of the activities of NK cells, LAK cells, and CTLs. It has been reported that NK cells, LAK cells, and CTLs induce cell death in tumors or virus-infected target cells by two main mechanisms. The first mechanism is direct release of cytolytic granules that contain the pore-forming protein perforin, several serine proteases termed granzymes, and granulysin by exocytosis to kill target cells, which is called the granule exocytosis pathway. The second mechanism is mediated by the Fas ligand (Fas-L)/Fas pathway, in which FasL (CD95 L), a surface membrane ligand of the killer cell cross links with the target cell's surface death receptor Fas (CD95) to induce apoptosis of the target cells. To date, it has been reported that OPs inhibit NK cell, LAK cell, and CTL activities by at least the following three mechanisms: 1) OPs impair the granule exocytosis pathway of NK cells, LAK cells, and CTLs by inhibiting the activity of granzymes, and by decreasing the intracellular levels of perforin, granzyme A, and granulysin, which were mediated by inducing degranulation of NK cells and by inhibiting the transcription of the mRNAs of perforin, granzyme A, and granulysin. 2) OPs impair the FasL/Fas pathway of NK cells, LAK cells, and CTLs, as investigated by using perforin-knockout mice, in which the granule exocytosis pathway of NK cells does not function and only the FasL/Fas pathway remains functional. 3) OPs induce apoptosis of immune cells.

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Objective: In this study, we aimed to determine how physicians can evaluate the severity of acute traumatic spinal cord injury (SCI) and predict the prognosis of this injury using the relationships of changes in clinical features and electrophysiological examination results.
Materials and Methods: Serial recordings of F-waves were performed on 20 consecutive cervical SCI patients. In 12 of the patients, changes in several parameters of F-waves which were elicited by median and ulnar nerve stimulations were examined by analyzing their relationships to clinical symptoms.
Results: The maximum amplitude of the F-waves (F-max) elicited by median nerve stimulation was found to be the most reliable (statistically significant) parameter for distinguishing clinically improved patients from nonimproved patients for the prognosis in the early stages after trauma. Other parameters, including the incidence of F-waves and the mean F-wave amplitude both of which were elicited by median nerve stimulation, were somewhat helpful for predicting the prognosis. These parameters of F-waves evoked by ulnar nerve stimulation could be useful for several weeks post-trauma.

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Background: Past studies suggested that plasma norepinephrine during exercise originates in sympathetic nerve endings and that the main origin differs among pathophysiological conditions.
Aims: This study investigated the most important site of sympathetic terminals as an origin of plasma norepinephrine during exercise in patients with heart failure using ¹²³I- metaiodobenzylguanidine (MIBG) scintigraphy.
Methods and Results: Twenty patients with organic heart disease underwent exercise testing and ¹²³I-MIBG scintigraphy. Systemic ¹²³I-MIBG uptake was measured 4 hours after ¹²³I-MIBG injection, and the heart-to-brain (H/B) and lower limb-to-brain ratios (L/B) were calculated. Plasma norepinephrine concentration was measured at rest and at peak exercise. Subjects were divided into two groups: those with preserved left ventricular ejection fraction (LVEF≥45%, n=8) and those with reduced LVEF (<45%, n=12). Plasma norepinephrine at rest did not correlate with H/B or L/B. In the preserved LVEF group, plasma norepinephrine at peak exercise was correlated with H/B (r=0.722), but not with L/B. In the reduced LVEF group, the norepinephrine response to peak exercise correlated with L/B (r=0.642), but not with H/B.
Conclusion: The present findings suggest that norepinephrine concentration is regulated by sympathetic terminal function of working muscles in patients with impaired LVEF and by that of the heart in patients with preserved LVEF.

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Background: The baroreflex has been reported to play an important role in hemodynamic regulation during exercise. Therefore, impairment of baroreflex function can induce an abnormal response of systolic blood pressure (SBP) to exercise, including exercise-induced hypertension. To clarify whether baroreflex function alters SBP response, we examined the relationship of baroreflex sensitivity (BRS) with SBP response to exercise.
Methods: In 22 subjects without cardiac dysfunction, BRS (ms/mmHg) was measured by the phenylephrine method, and a treadmill exercise test was administered according to Bruce's protocol.
Results: 1) The chronotropic response to exercise was higher in the normal BRS group than in the reduced BRS group (p<0.01). The SBP at the initial phase of exercise (1 min after the start of exercise) showed a smaller increase in the normal BRS group than in the reduced BRS group (p<0.01). During the initial phase of exercise, BRS had negative correlation with the SBP increment from rest (r=-0.408, p<0.05). During submaximal exercise (6 min after the start of exercise), a positive correlation between BRS and SBP response (r=0.422, p<0.05) was shown. 2) Subjects were divided into 2 groups: 12 subjects with normal BRS (≥5 ms/mmHg) and 10 subjects with reduced BRS (<5 ms/mmHg). During the initial exercise phase, the negative correlation between BRS and SBP response was stronger in the normal BRS group (r=-0.398) than in the reduced BRS group (r=-0.126). During submaximal exercise, BRS had a positive correlation with BP response to exercise in subjects with normal BRS (r=0.462).
Conclusion: Preserved baroreflex function is thought to be related to the pressor response to submaximal exercise, although the baroreflex is thought to be associated with the stabilization of blood pressure change during the initial exercise phase. These findings suggest that exercise-induced hypertension develops through the baroreflex mechanism.

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Objectives: The goals of this study were to determine the source of circulating endothelin-1 (ET-1) and interleukin-6 (IL-6) in acute myocardial infarction (MI) and to study the effects of coronary reperfusion (CR) on plasma levels of ET-1 and IL-6.
Methods: We serially measured plasma concentrations of ET-1 and IL-6 at different sampling sites before and after CR in patients with acute MI. A femoral vein (FV) catheter, a Swan-Ganz catheter, and a femoral artery (FA) catheter were placed in 25 patients with acute MI who were admitted within 12 hours after onset . For the measurement of ET-1 and IL-6 concentrations, blood samples from the FV, right atrium (RA), pulmonary artery (PA), and FA were collected before and 1 hour, 8 hours, and 24 hours after CR therapy. In 5 of the 25 patients, blood samples were collected through a coronary sinus (CS) catheter. We also assessed the gradient across 3 vascular beds (systemic, pulmonary, and coronary) as indices of the net release of ET-1 and IL-6 from those vascular beds. The maximal serum creatine kinase (CK) levels were assessed as an index of myocardial necrosis.
Results: ET-1 levels were higher in the FV than in the RA, PA, or FA. On CR, ET-1 levels peaked after 1 hour and returned to baseline by 24 hours. Calculated net release of ET-1 from the systemic vascular bed (ET-1 at FV-ET-1 at FA) was the highest among the 3 vascular beds. Plasma ET-1 levels correlated with hemodynamic parameters. Plasma IL-6 levels were similar among different sampling sites, whereas calculated net release of IL-6 from the coronary vascular bed was the highest among the 3 vascular beds. IL-6 levels increased throughout 24 hours after coronary reperfusion and closely correlated with maximal CK levels.
Conclusions: The present study suggests that, in acute MI, the major source of ET-1 maintaining baseline plasma levels is the systemic vascular bed and that the ET-1 levels presumably reflect the congestion. ET-1 levels peaked 1 hour after CR. IL-6 increased for 24 hours after CR. The major source of IL-6 is the coronary vascular bed. Only a slight correlation was observed between plasma ET-1 and IL-6 levels.

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One critical tumor-suppressive function of p53 is the induction of apoptosis in oncogene-expressing cells. In this context, p53-inducible genes encoding the BH3-only proteins of the Bcl-2 family, Noxa and Puma, were identified. Gene knockout studies revealed that both Noxa and Puma are involved in apoptosis induction in oncogene-expressing cells. BH3-only proteins induce apoptosis, and activate the downstream apoptosis effectors Bax and Bak. In this study, we found that Noxa and Puma synergistically activate Bax and Bak, and induce apoptosis. Although Noxa activates Bak by inactivating Mcl-1 and Bcl-X_L, gene knockdown studies revealed that neither Mcl-1 nor Bcl-X_L is involved in this synergism. Moreover, Puma, but not Noxa, directly activated Bax in the absence of Bak, and Noxa enhanced Puma-mediated Bax activation in Bak-deficient cells. These results suggest the existence of a novel regulatory pathway for Noxa-mediated apoptosis. Although we detected synergistic induction of apoptosis by Noxa and Bim, a tumor suppressive transcriptional factor FoxO3-inducible protein, no such synergism was observed for other pairs of BH3-only proteins, Bim and Bid, or Bim and Puma. From these results, it can be considered that p53 carefully controls apoptosis by allowing two molecules to share full ability to induce apoptosis.

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Background: The aim of this study was to investigate the advantages of laparoscopic hepatectomy over open surgery for liver tumors.
Patients and Method: A retrospective study was performed of 10 patients with liver tumors (9 with hepatocellular carcinoma and 1 with focal nodular hyperplasia) at our hospital. Five patients who had received laparoscopic hepatectomy (Lap-Hx group) were compared with 5 patients who had undergone open hepatectomy (O-Hx group) in the same period. The operative procedure was partial hepatectomy and cholecystectomy in both groups. For liver excision, a microwave coagulation device and an ultrasonically activated scalpel were used.
Results: Mean patient age was 55.6 ± 13.9 years in the Lap-Hx group and 51.8 ± 14.1 years in the O-Hx group. Four patients in the Lap-Hx group had hepatocellular carcinoma with liver cirrhosis and 1 patient had focal nodular hyperplasia. All patients in the O-Hx group had hepatocellular carcinoma and 4 patients had associated liver cirrhosis. The mean tumor size was 2.6 ± 1.5 cm in the Lap-Hx group and 3.0 ± 1.8 cm in the O-Hx group. The two groups did not thus differ significantly in the preoperative background factors. Blood loss and duration of the postoperative hospital stay were significantly less in the Lap-Hx than in the O-Hx groups(213 ± 82 vs 247 ± 97 min; 154 ± 128 vs 648 ± 468 ml, p=0.05: and 10.4 ± 2.3 vs 18.0 ± 5.1 days, p=0.017), but operating time did not differ significantly.
Conclusions: Laparoscopic hepatectomy has the advantages of reducing the amount of operative blood loss because of the magnified view afforded by the laparoscope and shortening the hospital stay. The procedure is therefore recommended for patients with appropriate liver tumors, in particular, hepatocellular carcinoma in the cirrhotic liver.

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Aims: Recently, endoscopic mucosal resection (EMR) has become the first choice of treatment for superficial esophageal cancer without metastasis. However, EMR is not safe for all patients. Argon plasma coagulation (APC) is a noncontact electrocoagulation technique that creates tissue damage. The risk of bleeding may be lower with APC than with EMR. Therefore, we selected APC for the treatment of patients with superficial esophageal cancer who could not undergo EMR. The aim of the present study was to describe these cases and analyze the results of this treatment.
Patients and Methods: Ten patients with superficial esophageal cancer underwent APC at our institution from February 2001 through January 2002. None of the patients could undergo EMR because of complications. Ablation was performed using an APC probe (ERBE APC probe; ERBE Elektromedizin, Tübingen, Germany), a high-frequency electrosurgical generator (ERBE ICC200), and an argon delivery unit (ERBE APC 300). All patients had uneventful recoveries.
Results: No incidents of bleeding from the ablated lesion or infection occurred. Oral intake was resumed on the day after treatment. The mean duration of the procedure was 20 minutes (range, 10 to 40 minutes). Disease recurred in two patients. Two patients died of laryngeal cancer and liver failure, respectively.
Conclusion: APC is a safe and easy to perform procedure, but the effect of therapy is inferior to that of EMR in terms of the complete resection of the lesion. In conclusion, APC should be limited to cases of superficial esophageal cancer without metastasis in which EMR has been deemed difficult.

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We report an intra-abdominal endocrine tumor possibly arising from an ectopic pancreas. A 45-year-old woman visited the Nippon Medical School Musashi-Kosugi Hospital because of right-sided hypochondralgia and upper abdominal discomfort of 1 years duration. An intra-abdominal tumor was diagnosed on the basis of the results of an ultrasound examination, computed tomography and magnetic resonance. Surgery was subsequently performed using laparoscopic techniques, and a tumor without firm adhesions was found near the wall of the duodenal bulbus. The tumor was easily removed; the resected specimen (55 × 45 × 25 mm, 50 g) was composed of bloody fluid within a cystic tumor. Histological and immunohistochemical examinations of the tumor showed a type 3 ectopic pancreas, according to the classification proposed by Heinrich. The patients recovery was uneventful.

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A 10-year-old boy had undergone conventional two-stage surgery that includeed repair of aortic coarctation with pulmonary artery banding as an initial operation followed by closure of a ventricular septal defect as a secondary procedure. Following these procedures, aortic coarctation recurred, and balloon angioplasty was performed three times. Aortic recoarctation, however, persisted, and aortic stenosis and regurgitation and pulmonary stenosis gradually developed. An operation was therefore performed to repair recoarctation, aortic stenosis and regurgitation, and pulmonary stenosis. Patch aortoplasty was performed for recoarctation. The aortic valve was replaced with a 19 mm On-X valve, with Konno root enlargement. Pulmonary arterial patch plasty was also performed. During aortic arch reconstruction, selective cerebral perfusion was performed via the innominate artery and left carotid artery, and the lower half of the body was perfused through a cannula in the left femoral artery. The postoperative course was uneventful, and aortography revealed a well-reconstructed aortic arch free of obstruction. There were no valve-related complications.

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