The tumor promoters 12-O-tetradecanoylphorbol-13-acetate and okadaic acid differ in toxicity, mitogenic activity and induction of gene expression

Okadaic acid (OA) and 12-O-tetradecanoylphorbol-13-acetate (TPA)are both potent tumor promoters in a mouse skin carcinogenesisexperiment. OA was much more toxic than TPA for murine embryocell lines such as Swiss 3T3 cells or C3H10T? cells. TPA isa potent mitogen for 3T3 cells; in contrast OA was unable tostimulate DNA synthesis in these cells. TPA induces a familyof primary response genes, the TPA induced sequence (TIS) genes,in a wide variety of cells. Although OA induced modest levelsof TIS mRNA expression, the time course of the induction ofTIS1 and TIS8 mRNA was delayed when compared to induction byTPA or peptide mitogeas such as fibroblast growth factor (FGF).In addition TPA-mediated down-regulation of protein kinase Cattenuated TIS gene induction by OA, but not by FGF.     

Release of heat-loss responses in paradoxical sleep by thermal loads and by pontine tegmental lesions in cats

Thermoregulatory heat-loss responses at high ambient temperatures were studied in intact cats and those with bilateral electrolytic lesions in the pontine tegmentum during wakefulness (W), slow-wave sleep (SWS), paradoxical sleep (PS) and PS without atonia induced by the lesions. Panting (respiratory rate 90/min) was present W, SWS, and in some cases, during PS. The percentage of the PS episodes with panting was directly related ambient temperature. In intact cats at 30 °C, panting occurred in 8% of the PS episodes; at 35 °C, in 52%, and at 40 °C, in 77%. The percentage of PS episodes with panting higher in the pontine-lesioned cats (90% at 35 °C), probably another indication of the altered thermoregulation of such animals. Thermoregulatory responses to heat load, and thermoregulation in general, have previously been shown to be suppressed in PS. Because hypothalamic thermosensitive neurons lack thermal responses during PS, the partial activation of heat-loss responses observed here may depend upon the function of extrahypothalamic brainstem areas.     

Electrocardiographic changes during and after isoflurane-induced hypotension for neurovascular surgery

We evaluated the effects of isoflurane anaesthesia and induced hypotension in 33 neurosurgical patients by electrocardiographic monitoring and serial cardiac enzyme measurements. An electrocardiogram (ECG) and serum enzymes were obtained preoperatively, intraoperatively and postoperatively in the recovery room and for three consecutive days. ECG leads II, V1 and V5 were monitored continuously during anaesthesia. Patients who had had a subarachnoid haemorrhage and a high incidence of abnormal preoperative ECG (42 per cent). Ten patients developed ECG changes intraoperatively, but these changes were unrelated to isoflurane-induced hypotension. Fifty-three per cent of patients developed an abnormal postoperative ECG. These abnormalities consisted mostly of nonspecific ST segment or T wave changes. At no time was there an elevation in cardiac enzyme activity. We found that nonspecific ECG changes are relatively common in patients undergoing vascular neurosurgical procedures. There was no enzymatic evidence of myocardial infarction and we can only speculate that these ECG changes are related to intracranial surgical manipulation.     

Purification of the human blood platelet thromboxane A2/prostaglandin H2 receptor protein.

The human platelet thromboxane A2/prostaglandin H2 receptor has been purified 6100-fold to apparent homogeneity by a three-step chromatographic procedure with an overall yield of 6%. A 6-fold purification of the receptor was first achieved by chromatography of 3-[(3-cholamidopropyl)dimethyl-ammonio]-1-propanesulfonate (CHAPS)-solubilized membrane proteins from human platelets on a diethylaminoethyl (DEAE)-Sepharose column. The DEAE eluate fractions containing receptor activity were then applied to a newly developed affinity column using the cyclohexyl derivative of SQ30,741 (SQ31,491) as the immobilized ligand. Elution of the receptor from the affinity column with BM13.177 yielded a further purification of 1700-fold. An additional 4-fold receptor purification from the affinity column eluate was achieved by HPLC using GPC 500 and GPC 100 columns connected in tandem. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining of the HPLC eluate containing purified receptor revealed a single, distinct band with a molecular weight of 55,000. The receptor binding activity was detected with [3H]SQ29,548 using a newly developed binding assay which involved immobilization of the receptor on polyethyleneimine-treated glass fiber filters. The binding of [3H]SQ29,548 to the purified receptor was time dependent, saturable, reversible and highly specific. Unlabeled SQ29,548, BM13.505, and U46619 (but not thromboxane B2 or 6-keto prostaglandin F1 alpha) competed for [3H]SQ29,548 binding to the purified receptor in a concentration-dependent manner. Scatchard analysis of [3H]SQ29,548 binding to the purified receptor revealed the presence of a single class of high-affinity binding sites, with a Kd of 4 nM and a Bmax of 17 nmol/mg protein.     

Changes in blood pressure and vasoactive hormones during volume expansion in stable patients on chronic haemodialysis

Summary: We studied changes in blood pressure (BP) and plasma hormones (atrial natriuretic peptide [ANP], brain natriuretic peptide [BNP], endothelin [ET], angiotensin [AII] and renin [PRA]) in four stable haemodialysis patients 48 h after a routine dialysis (basal stat), after volume expansion (4–7% above dry bodyweight) for 4 days then 48 h later following ultrafiltration. Blood pressure rose and plasma AII and PRA values fell with volume expansion and returned to baseline at the end of the study. Endothelin values were unchanged. Plasma ANP and BNP rose similarly in three patients and returned to near baseline levels after ultrafiltration. Sustained volume expansion over 4 days in dialysis patients is associated with an increase in BP, a marked elevation in plasma ANP and BNP but without change in ET.     

Should all the N3 lymph nodes group metastasis be regarded as distant metastasis (M1) in curatively resected gastric cancer?

Recently, metastasis to N3 lymph nodes group was regarded as distant metastasis by the new TNM staging system due to poor overall survival. However, the 5-year overall survival rate of patients with metastasis to N3 groups was 34.5% after curative surgery. Moreover, in patients with metastasis to lymph node subgroups of #12, #13, #14, the overall 5-year survival rate increased upto 47.2% after curative resection and adjuvant chemotherapy. This was similar to that of the patients with metastasis to N1 and N2 lymph nodes groups. But in these highly tumor burden states, no survival benefit was found with the addition of immunotherapy to chemotherapy as we achieved in stage II and III. Therefore, we suggest that, at least, metastasis to #12, #13, #14 lymph nodes subgroups should not be categorized as a distant metastasis. And in these situations, active curative radical surgery with extended lymphadenectomy and adjuvant chemotherapy are recommended.     

多巴酚丁胺负荷对缺血性扩张型心肌病患者左心室充盈的影响：病理生理学及预后意义

目的：本研究旨在探讨多巴酚丁胺对缺血性心肌病（ICM）患者左心室（LV）充盈功能的影响，并确定峰值负荷时限制性充盈型（RFP）是否具有预后预测价值。背景：ICM患者峰值负荷时RFP的预后价值尚属未知。方法：在静息和负荷情况下，采用多普勒超声心动检查研究了69例ICM患者；RFP定义为跨二尖瓣E／A比≥1．0、等容舒张时间（IVRT）〈80ms及E波减速时间（EDT）〈120ms。结果：69例患者中有42例静息时出现RFP，其中有24例患者负荷情况下转变为非RFP（EA），18例患者RFP持续存在（EE）；69例患者中27例静息和峰值负荷时均无RFP（AA）。