Soluble asialoglycoprotein receptors reflect the apoptosis of hepatocytes

Cell death is thought to take place through at least two distinct processes: apoptosis and necrosis. There is increasing evidence that dysregulation of the apoptotic program is involved in liver diseases. However, there is no method to simply evaluate apoptosis in the liver tissue at present. It has been reported that the expression of asialoglycoprotein receptors (AGPRs) increases with apoptosis, but there is no report until now that investigates the influence of soluble AGPRs on apoptosis of hepatocytes. Soluble AGPRs have been reported to be present in human serum under physiological conditions. In the present study, in order to investigate the correlation between apoptosis of hepatocytes and soluble AGPR, mouse soluble AGPRs were detected using SDS-PAGE and Western blot analysis was conducted using anti-extracellular mouse hepatic lectin-1 (Ex-MHL-1) antiserum (polyclonal rabbit serum). The mouse soluble AGPRs were present in culture medium and mouse serum when hepatocytes were damaged. The soluble AGPRs increased proportionately, as the number of dead hepatocytes increased. In addition, soluble AGPRs existed more when apoptotic cell death was observed in in vitro and in vivo than when necrotic cell death was observed. The extracellular moiety of MHL-1 exists in the culture medium and mouse serum as a soluble AGPR, but the detailed mechanism of releasing soluble AGPR from hepatocytes has not been revealed yet. We described the first evidence for the relation between quantity of soluble AGPRs with two kinds of cell death: necrosis and apoptosis. Based on the results of our study, soluble AGPRs might become a new marker of apoptosis in the liver tissue and be useful for clinical diagnosis and treatment for liver diseases.     

General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug for xerostomia in Sjögren's syndrome. 4th communication: Effects on gastrointestinal,urinary and reproductive systems and other effects

A novel muscarinic receptor agonist, SNI-2011 ((+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), is a candidate therapeutic drug for xerostomia in Sj?gren's syndrome. The general pharmacological properties of this drug on the gastrointestinal, urinary and reproductive systems and other tissues were investigated in mice, rats guinea pigs, rabbits and dogs. 1. Gastrointestinal system: SNI-2011 did not cause any effects on the gastrointestinal system, i.e. the intestinal transport of charcoal meal in mice, the secretion of gastric and bile juices, and the formation of ulcer induced by water immersion restraint in rats. 2. Urinary and reproductive systems: SNI-2011 augmented the spontaneous movement of rat pregnant uterus in vivo at 0.3 mg/kg i.v. or higher, and this effect was not observed in the non-pregnant uterus. SNI-2011 increased the spontaneous movement of isolated guinea pig bladder (3 x 10(-6) mol/l or higher) and increased the in vivo spontaneous movement of rat bladder (0.3 mg/kg i.v. or higher). SNI-2011 caused increases in rat urine volume, pH and urinary excretion of Na+ and Cl- at 30 mg/kg p.o. 3. Others: SNI-2011 had no effect on the vascular permeability in mice, hematological parameters and blood coagulation in rats. SNI-2011 had neither hemolytic nor anti-inflammatory effect. These results suggest that SNI-2011 has muscarinic effects on the gastrointestinal, urinary and reproductive systems and other tissues at the doses approximately 10-fold higher than the doses needed for saliva secretion.     

General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug for xerostomia in Sjögren's syndrome. 2nd communication: effects on somatic nervous system and on autonomic nervous system and smooth muscle

A novel muscarinic receptor agonist SNI-2011 ((+/-)-cis-2-methylspirol[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), is a candidate therapeutic drug for xerostomia in Sj?gren's syndrome. The general pharmacological properties of this drug on the somatic nervous system and on the autonomic nervous system and smooth muscle were investigated in mice, rats, guinea pigs, rabbits and cats. 1. Somatic nervous system: SNI-2011 had no effect on the neuromuscular junction in rats and no muscle relaxant effect in mice. No surface anesthetic effect was observed in guinea pigs, but infiltration anesthetic effect was found after intracutaneous injection of solution (1% or higher). 2. Autonomic nervous system and smooth muscle: SNI-2011 tended to cause mydriasis at 3 mg/kg i.v. or higher in rabbits and dose-dependently caused mydriasis at 10 mg/kg p.o. or higher in rats. Mydriasis in rats was also observed by ophthalmic instillation, caused via the peripheral muscarinic acetylcholine receptors. SNI-2011 elevated the base line tension of nictitating membrane in cats when it was injected intravenously at 3 mg/kg or higher. In the smooth muscle, SNI-2011 increased the spontaneous movement of isolated rabbit ileum (1 x 10(-6) mol/l or higher), contractions of isolated guinea pig ileum (1 x 10(-6) mol/l or higher) and isolated guinea pig trachea (3 x 10(-6) mol/l or higher). SNI-2011 relaxed the histamine- and noradrenaline-induced contractions of isolated guinea pig aorta and augmented noradrenaline- and phenylephrine-induced contractions of isolated rat vas deferens. These effects were induced by relatively higher concentrations only i.e. 1 x 10(-5) mol/l or higher. From these results, SNI-2011 has muscarinic side effects on the somatic nervous system and on the autonomic nervous system and smooth muscle, however, in the case of oral administration, that is clinical administration route, SNI-2011 caused no muscarinic side effect at the effective doses needed for saliva secretion.     

Follow- up of coronary artery lesions caused by Kawasaki disease and the val ue of coronary angiography

目的：探讨川崎病后冠 状动脉病变及转归,以及二维超声心动图和选择性冠状动脉造影在冠状动脉病变判断和长期随访中的作用。方法：1979-1997年因川畸病在治疗和随访中发现有冠状动脉病变的87例,最长随访时间为16年6月。随访时给予阿斯匹林或阿斯匹林加华法令口服。每个病人每隔1-3年进行选择性冠状动脉及左室造影检查,直至正常。总共行选择性冠状动脉及左室造影167次,每次造影前均行二维超声心动图检查。结果：造影发现48/87（55％）病儿的冠状动脉病变在随访过程中消失,6/87（7％）病儿出现严重的冠状动脉病变导致明显的心肌缺血或心肌梗塞而需行冠状动脉搭桥手术。随着随访时间的延长,狭窄或血栓性冠状动脉病变的比例逐渐增高,冠状动脉瘤的比例逐渐降低。造影与二维超声心动图对照研究发现二维超声心动图检查存在假阳性和假阴性。二维超声心动图检查冠状动脉瘤的发现率为76％,狭窄或血栓性病变的发现率为18％,不能发现远端冠状动脉的狭窄或血栓性病变。结论：长期随访发现55％病儿的冠状动脉病变可以恢复正常,7％的病儿可发展成严重的冠状动脉病变。川崎病病儿均需长期随访,当出现严重冠状动脉病变时需及时处理。二维超声心动图检查不能替代选择性冠状动脉造影作川崎病后冠状动脉病变的长期随访。     

Diagnosis of deep vein thrombosis using multi-detector helical CT

PURPOSE: To evaluate the usefulness of multi-detector helical CT (MDHCT) with contrast medium in the diagnosis of deep vein thrombosis (DVT). Materials and Methods: The bilateral veins of the dorsal pedis in 45 patients (12 men, 33 women; average age, 64 years) under clinical suspicion of DVT were first punctured using 22-G needles. Then CT scanning from the level of the foot to the inferior vena cava was started 20 sec after the initial injection of 200 mL of dilute contrast medium (50 mL nonionic iodinated contrast medium of 300 mgI/mL and 150 mL saline) at a rate of 5 mL/sec. RESULTS: Two patients were excluded because of unsuccessful venous puncture. The average scanning time in 43 patients was 38.5 +/- 7.9 seconds. Images of veins from the foot to the inferior vena cava were clearly demonstrated in each case. MDHCT showed DVT in 32 cases and patent deep vein in 11 cases. Simultaneous venography of the lower extremity in 18 patients clearly visualized DVT at the same level detected by contrast MDHCT. CONCLUSION: MDHCT for the diangosis of DVT has the advantages of wider scanning range, shorter scanning time, and finer Z-axis resolution than the other diagnostic modalities.     

Carbon ion radiation therapy for prostate cancer: results of a prospective phase II study.

BACKGROUND AND PURPOSE: To determine the efficacy and feasibility of carbon ion radiotherapy (C-ion RT) for prostate cancer. PATIENTS AND METHODS: Between April 2000 and November 2003, 175 patients received C-ion RT using a recommended dose fractionation (66.0 GyE/20 fractions) established from prior studies. C-ion RT alone was performed for 33 patients constituting a low-risk group (Stage < or =T2a and PSA <20 ng/ml and Gleason score < or =6); the remaining 142 high-risk patients received an additional androgen deprivation therapy (ADT). RESULTS: The 4-year overall survival and bNED rates were 91% and 87%, respectively. Local control was achieved in all but one patient. The 4-year bNED rates were 87% in the low-risk group and 88% in the high-risk group. In very advanced diseases (Stage > or= T3a or PSA > or= 20 ng/ml or Gleason score > or =8), there was significant difference in the bNED rate according to period of ADT administration (ADT > or =24 months: 93%, ADT <24 months: 73%, p<0.01). Grade 2 late toxicities developed in 4 patients (2%) for the rectum and 9 patients (5%) for the genitourinary system but no Grade 3 or higher toxicity was observed. CONCLUSIONS: The effectiveness of C-ion RT for prostate cancer has been well confirmed. Based on these results, new study of a C-ion RT modified for the administration strategy of ADT according to the patient risk has been started by dividing patients into 3 groups, high-risk, intermediate-risk, and low-risk.     

Suppression of Postmitochondrial Signaling and Delayed Response to UV-induced Nuclear Apoptosis in HeLa Cells

Activation of postmitochondrial pathways by UV irradiation was examined using mouse lymphoma 3SB and human leukemic Jurkat cells and two human carcinoma cell lines (HeLa and MCF-7). Exposure of 3SB and Jurkat cells resulted in large amounts of cytochrome c and apoptosis-inducing factor (AIF) being released into the cytosol, and a clear laddering pattern of DNA fragments was observed within 3 h of incubation after irradiation. Simultaneously, activation of caspase-9 and its downstream caspases was detected. HeLa and MCF-7 cells also showed extensive release of mitochondrial factors and caspase-9 activation at 4 to 6 h after exposure, but apoptotic nuclear changes appeared much later. Compared with 3SB and Jurkat cells, these carcinoma cell lines exhibited reduced activation of caspase-9-like proteolytic activity by UV radiation, and levels of caspase-3-like activity in HeLa cells were extremely low, similar to those in caspase-3-deficient MCF-7 cells. These results suggest that the delayed response to UV-induced nuclear apoptosis in HeLa cells is due to a reduced activation of the caspase cascade downstream of cytochrome c release and suppression of caspase-3 activity.     

Transient phrenic nerve palsy after cardiac operation in infants.

OBJECTIVE: The aims of this study were to prove the presence of transient phrenic nerve palsy in children after cardiac surgery by successive recordings of diaphragmatic action potentials (DAPs), and to decide the indication of diaphragmatic plication in infants with postoperative phrenic nerve palsy. METHODS: The DAPs were recorded from 11 infants (age 0-54 months) under artificial ventilation after cardiac surgery. The successive DAP recordings were performed within 3-4 days (0W), 1 week (1W) and 2 weeks (2W) after operation to make a final decision for diaphragmatic plication to wean artificial ventilation. RESULTS: The patients were divided into 3 groups according to the DAP changes in successive recordings, namely, patients with normal DAPs at 0W, patients with transient depression of DAPs at 0W followed by recovery to normal DAPs by 1W and/or 2W, and patients with persistent depression of DAPs of the affected side necessitating plication of hemidiaphragm. CONCLUSIONS: In infants with phrenic nerve palsy after cardiothoracic surgery, persistently abnormal DAPs in repeated electrophysiologic examinations for at least 2 weeks after surgery are a useful guidance to support clinical and radiological evidence for an indication of diaphragmatic plication.     

Wolff-Parkinson-White (WPW) syndrome in isolated noncompaction of the ventricular myocardium (INVM).

Isolated noncompaction of the ventricular myocardium (INVM) is a rare morphological abnormality caused by cessation of the compaction of the loose interwoven meshwork of myocardial fibers during intrauterine life. Three cases of INVM, including 2 siblings, were diagnosed from 2-dimensional echocardiographic findings of Wolff-Parkinson-White syndrome type B to which INVM can be attributed.