No abstract

Background. Recently, the authors reported that membrane‐associated phospholipase A2 (M‐PLA2) was one of the acute phase reactants and increased in serum of patients with various malignant tumors. Methods. M‐PLA2 concentrations in tissue specimens from 78 breast cancers, 16 benign breast tumors, and 10 normal breast tissues were determined by a specific radioimmunoassay recently developed. Immunohistochemical staining was performed on all specimens by the avidin‐biotin‐peroxidase method. Results. Tissue levels of M‐PLA2 concentration were significantly higher in breast cancer than in benign breast tumor or normal breast tissue (P < 0.01). Correlation analyses between the tissue concentration of M‐PLA2 and clinicopathologic factors showed that tissue M‐PLA2 levels were significantly higher in patients with skin or muscle invasion, vessel involvement, and distant metastasis than in those without. In addition, this enzyme concentration was significantly greater in scirrhous carcinoma than in papillotubular or solid‐tubular carcinoma. No association was found between M‐PLA2 concentration and steroid hormone receptor status. Immunohistochemically, M‐PLA2 was preferentially stained in the invading zone of breast cancer tissues, especially in scirrhous carcinoma. Patients with breast cancer with low levels of M‐PLA2 showed significantly longer overall survival and disease‐free survival compared with those with high levels of this enzyme at the cutoff point of 50 ng/100 mg protein. The combination of estrogen receptor status with M‐PLA2 concentration could be a powerful prognostic factor in predicting such survival rates. Conclusions. M‐PLA2 is closely related to the malignant potential of breast cancers, and the M‐PLA2 contents in breast cancer tissues could be a new valuable prognostic factor, other than the hormone receptor, in delineating the status of human breast cancer.

Background and Purpose— The strong evidence of endovascular therapy in acute ischemic stroke patients with large vessel occlusion (LVO) is revealed. Such patients are required to direct transport to the hospital capable of endovascular therapy. There are several prehospital scales available for paramedics to predict LVO. However, they are time consuming, and several of them include factors caused by other types than LVO. Therefore, we need a fast, simple, and reliable prehospital scale for LVO. Methods— We developed a new prehospital stroke scale, emergent large vessel occlusion (ELVO) screen, for paramedics to predict LVO. The study was prospectively performed by multistroke centers. When paramedics referred to stroke center to accept suspected stroke patients, we obtain the following information over the telephone. ELVO screen was designed focusing on cortical symptoms: 1 observation; presence of eye deviation and 2 questions; paramedics show glasses, what is this? and paramedics show 4 fingers, how many fingers are there? If the presence of eye deviation or ≥1 of the 2 items were incorrect, ELVO screen was identified as positive. We evaluated between results of ELVO screen and presence of LVO on magnetic resonance angiography at hospital arrival. Results— A total of 413 patients (age, 74±13 years; men, 234 [57%]) were enrolled. Diagnosis was ischemic stroke, 271 (66%); brain hemorrhage 73 (18%); subarachnoid hemorrhage, 7 (2%); and not stroke, 62 (15%). One hundred fourteen patients had LVO (internal carotid artery, 33 [29%]; M1, 52 [46%]; M2, 21 [18%]; basilar artery, 5 [4%]; P1, 3 [3%]). Sensitively, specificity, positive predictive value, negative predictive value, and accuracy for ELVO screen to predict LVO were 85%, 72%, 54%, 93% and 76%, respectively. Among 233 patients with negative ELVO screen, only 17 (7%) had LVO, which indicated to be an ideal scale to avoid missing endovascular therapy. Conclusions— The ELVO screen is a simple, fast, and reliable prehospital scale for paramedics to identify stroke patients with LVO for whom endovascular therapy is an effective treatment.

SummaryBreast cancer cells are known to express various proteolytic enzymes, which make them invasive and favour their dissemination to distant sites. However, it is unclear whether breast cancer cells have the ability to produce polymorphonuclear leucocyte elastase (PMN-E). We measured immunoreactive (ir) PMN-E content in the conditioned medium of two breast cancer cell lines, MCF-7 and ZR-75-1, and two normal breast epithelial cell lines, HBL-100 and Hs 578Bst, using a highly specific and sensitive enzyme immunoassay. (4.23 ± 3.74 gg 100 mg-' protein) patients. Breast cancer patients with high levels of ir-PMN-E showed significantly shorter disease-free survival and overall survival than those with low levels of ir-PMN-E at the cut-off point of 8.99 lg 100 mg-' protein. In the multivariate analysis, ir-PMN-E content was found to be a significant prognostic factor for disease recurrence and death in human breast cancer.Considerable evidence suggests that proteolytic enzymes are involved in cancer invasion and metastasis (Mignatti et al., 1986;Persky et al., 1986). Production of tumour cell proteinases, including plasminogen activator (Duffy et al., 1987;Reich et al., 1988;Yamashita et al., 1993a), collagenase (Turpeenniemi-Hujanen et al., 1985), and cathepsin B (Recklies et al., 1980) has been implicated in tumour cell invasion into adjacent tissues and metastasis. Another proteinase that has attracted attention as a mediator of these processes is elastase. Elastase is the only proteinase that is able to degrade insoluble elastin (Janoff & Schere, 1968), a structural component of elastic tissues such as blood vessels, skin, lung and breast tissue.An elastinolytic activity has been demonstrated previously by Hornebeck et al. (1977) in tissue extracts from human breast cancer, but in their study it was not determined whether the activity could be attributed to tumour cells. Thereafter, several investigators have reported that elastinolytic activity is found in the culture medium of mouse mammary tumour cells (Grant et al., 1990;Zeydel et al., 1986) and human breast cancer cells (Kao et al., 1982), suggesting that elastinolytic enzymes are produced by the tumour cells themselves.Very recently, a highly specific and sensitive enzyme immunoassay (EIA) was established for the measurement of human polymorphonuclear leucocyte elastase (PMN-E) (Ikei et al., 1992). Labelled antibody in this assay recognises not only PMN-E complexed a,-proteinase inhibitor but also the free form of PMN-E, which may present in the enzyme samples. In the present study, we examined whether breast cancer cells have the ability to produce immunoreactive (ir)-PMN-E. Furthermore, we have determined the concentration of ir-PMN-E in tissue extracts from human breast cancer, and elucidated the relationship between the tissue content of ir-PMN-E and clinicopathological status in human breast cancer. Materials and methods Cell cultureThe human breast cancer cell line MCF-7 was kindly provided by Y. Nomura (National Kyushu Cancer Center Hospital, Fu...

ABSTRACT. Lipid and lipoprotein concentrations and apolipoprotein profile were investigated in canine pancreatitis induced by infusion with oleic acid (OA) into the accessory pancreatic duct. Pancreatitis was diagnosed by physical, hematological, biochemical and pathological examinations. In OA-treated dogs, serum triglyceride (TG) concentration was increased; however, there were no changes in serum total cholesterol (TC) and phospholipid (PL) concentrations. Serum concentrations of TG, TC, PL and total lipids (TL) in beta lipoprotein and those of TC, PL and TL in pre-beta lipoprotein were increased and those of TC, PL and TL in alpha 1 lipoprotein were decreased. In apolipoprotein profile, the proportions of apolipoprotein B100 in low density lipoprotein fraction and apolipoprotein A-IV in high density lipoprotein fraction were increased. In addition, decreased proportion of apolipoprotein A-I and the appearance of serum amyloid A protein in high density lipoprotein fraction were observed. These results suggest that lipoprotein profiles observed in canine acute pancreatitis are attributed to the alterations in apolipoprotein compositions. -KEY WORDS: apolipoprotein, canine, lipid, lipoprotein, pancreatitis.J. Vet. Med. Sci. 60(4): 413-421, 1998 in clinical pancreatitis [15,27], increase of TG are not observed in these experimentally induced pancreatitis [4,27]. Therefore, hyperlipidemia in acute pancreatitis might not be reproduced by ligation of pancreatic duct and infusion with mixture of bile and trypsin. In this study, induction of canine acute pancreatitis was attempted by the infusion with oleic acid (OA) into pancreatic duct. Hyperlipidemia is brought by changes of lipoprotein metabolism. Apolipoproteins are structural proteins and participate in lipoprotein metabolism. Changes of apolipoprotein composition bring about abnormality in lipoprotein metabolism. Analysis of apolipoprotein is important to understand the changes of lipoprotein metabolism; however, there is no report on serum apolipoprotein profile in canine pancreatitis. The purpose of this study is to examine the effects of acute pancreatitis induced with OA on serum lipid and lipoprotein concentrations and apolipoprotein profile in dogs. MATERIALS AND METHODSExperimental animals: Eight male beagle dogs, weighing 10.5 to 14.5 kg and aged over one year were used. These dogs were divided into two groups. OA-treated dogs were injected with OA (Sigma Chemical Co., U.S.A.) and control dogs were injected with physiological saline (PS; Otsuka Seiyaku Co., Ltd., Tokyo).Surgical manipulation and inducing pancreatitis: Operative procedures were performed on the dogs after premedication with atropine sulfate (Tanabe Seiyaku Co., Ltd., Osaka) and xylazine hydrochloride (Bayer Japan Co., Ltd., Tokyo) and induction with sodium thiamylal (Yoshitomi Seiyaku Co., Ltd., Osaka) and under inhalation anesthesia with isoflurane (Dainabot Co., Ltd., Tokyo). Laparotomy through a midline approach and duodenotomy was done. A flexible 22-gauge needle was inserted via...