Biomedical subjects

Y Nagashima

Publications and source records attributed to Y Nagashima.

At least 91 records · Page 5Linked to original sources

PubMed1998

Inhibition of inducible nitric oxide synthase prevents LPS-induced acute lung injury in dogs.

Nitric oxide (NO) is produced by inducible NO synthase (iNOS) after LPS stimulation, and reacts with superoxide to form peroxynitrite. We hypothesize that in LPS-induced lung injury, NO generated by iNOS plays a key role through the formation of peroxynitrite. We developed an acute lung injury dog model by injecting LPS, and examined the effects of selective iNOS inhibitors, aminoguanidine (AG) and S-methylisothiourea sulfate (SMT), on the LPS-induced lung injury. At 24 h after LPS injection, arterial oxygen tension and mean arterial pressure decreased, and shunt ratio and lung wet-to-dry weight ratio increased. On histology, the LPS group had marked neutrophil infiltration and widening of the alveolar septa. On immunohistochemistry, iNOS and nitrotyrosine, a major product of nitration of protein by peroxynitrite, were observed in the interstitium, capillary wall, and neutrophils in the airspaces of the LPS group. Treatments with AG and SMT prevented worsening of gas exchange, hemodynamics, and wet-to-dry weight ratio. On histology, AG and SMT treatments markedly suppressed lung injury, iNOS protein, and nitrotyrosine production. We conclude that NO released by iNOS may play a critical role in the pathogenesis of LPS-induced acute lung injury. This study suggests that iNOS inhibitors may have potential in the treatment of LPS-induced acute respiratory distress syndrome.

Animals↗

PubMed1998

Differential expression of trypsin in human ovarian carcinomas and low-malignant-potential tumors.

It is widely recognized that matrix metalloproteinases and serine proteinases play an important role in cancer invasion and metastasis. We have reported that trypsin is synthesized in ovarian carcinomas as well as in some other types of cancers. In general, ovarian cancers easily tend to invade, metastasize, and spread widely into the peritoneal cavity. However, low-malignant-potential (LMP, borderline tumor) ovarian tumors are known to have limited malignant potential for progression, although microinvasion and distant metastasis have been reported among them. To analyze the relationship between varied degrees of trypsin expression and malignant behavior of ovarian tumors, immunohistochemical studies with monoclonal antibodies to human trypsin and clinicopathologic analysis were performed in human ovarian carcinomas, low-malignant-potential tumors, and benign cystadenomas. Thirteen (44.8%) cases of 29 ovarian carcinomas showed prominent trypsin expression, while only 2 (18.2%) cases of 11 LMP ovarian tumors demonstrated low levels of expression. Benign tumors and normal ovaries did not show any positivity for trypsin. These data suggest that tumor-derived heterotropic trypsin may be associated with ovarian tumors in parallel with malignant potential or behavior such as invasiveness or metastasis. At least in some ovarian carcinomas, prominent stromal invasion or metastasis might require the acquisition of or association with tumor-derived trypsin production.

Female↗

PubMed1998

Heparin-binding epidermal growth factor-like growth factor stimulates mitogenic signaling and is highly expressed in human malignant gliomas.

We previously reported that schwannoma-derived growth factor (SDGF), a member of heparin-binding epidermal growth factor (EGF) family, participates in autocrine pathways and promotes rat glioma cell growth. To investigate the potential role of similar molecules in human gliomas, we examined 7 human glioma cell lines and 11 glioblastoma specimens for expression of the human homologue of SDGF, amphiregulin (AR), as well as heparin-binding EGF-like growth factor (HB-EGF). Northern blot analysis revealed that only one cell line and no tumor specimens expressed AR mRNA. In contrast, HB-EGF mRNA was expressed in all human glioma cell lines and its level of expression was two- to five-fold higher than that of control brain tissues in 8 of 11 glioblastoma cases. Immunohistochemistry demonstrated that membrane-anchored HB-EGF (proHB-EGF) and EGFR were co-expressed in 44% of 34 human malignant gliomas. Introduction of exogenous HB-EGF (10 ng/ml) increased human glioma cell proliferation, and anti-HB-EGF blocking antibodies reduced the growth of glioma cells by 30-40%, confirming the presence of an autocrine loop. When added to the medium, transforming growth factor-alpha, basic fibroblast growth factor, or HB-EGF rapidly induced HB-EGF mRNA expression. These results indicate that HB-EGF and proHB-EGF contribute to the growth of human malignant glioma cells, most likely through autocrine and juxtacrine mechanisms.

Amphiregulin↗

PubMed1998

Expression of trypsin by epithelial cells of various tissues, leukocytes, and neurons in human and mouse.

It has long been believed that trypsin is normally synthesized only in the pancreas. In the present study, expression of trypsin in human and mouse nonpancreatic tissues was examined. Northern blot analysis of normal human tissues indicated that the trypsin gene is expressed at high levels in the pancreas and spleen and considerably in the small intestine. However, in situ hybridization and immunohistochemistry demonstrated that trypsin is widely expressed in epithelial cells of the skin, esophagus, stomach, small intestine, lung, kidney, liver, and extrahepatic bile duct, as well as splenic and neuronal cells. In the spleen, trypsin message was detected in macrophages, monocytes, and lymphocytes in the white pulp. In the brain, it was detected in the nerve cells of the hippocampus and cerebral cortex. Analysis by gelatin zymography confirmed the presence of a latent or an active form of trypsin in various normal mouse tissues. Reverse transcription-polymerase chain reaction analysis also confirmed the expression of trypsin genes in the spleen, liver, kidney, and brain of normal mice. Such a broad distribution of trypsin suggests its general roles in the maintenance of normal epithelial cell functions, the immune defense system, and the central nervous system.

Animals↗

PubMed1998

Purification and properties of phospholipases A2 from the crown-of-thorns starfish (Acanthaster planci) venom.

Two phospholipases A < inf2 (named AP-PLA2-I and II) were purified from the crown-of-thorns starfish (Acanthaster planci) venom. Both enzymes were confirmed to be PLA2s, based on the results that they showed hemolytic activity only in the presence of phosphatidylcholine (PC) and also released fluorescent fatty acids from PC with labeled fatty acids at the sn-2 position. The enzyme activity of both PLA2s was enhanced by Ca2+ but reduced by Cu2+ and Zn2+. The molecular mass of AP-PLA2-I was estimated to be 28 kDa by gel filtration and 15 kDa by SDS-PAGE, indicating that AP-PLA2-I is a dimer composed of the same subunit. In contrast, AP-PLA2-II was judged to be a monomer with a molecular mass of 12 kDa (gel filtration) or 15 kDa (SDS-PAGE). The amino acid compositions of the two enzymes were comparable to each other; Asx, Glx and Gly were rich in both molecules, while Met, His and Trp were poor. Analyses by a sequencer determined the first 62 amino acid residues for both PLA2s. In the AP-PLA2-I preparation, minor amino acids were additionally found at 17 positions, suggesting the coexistence of another PLA2-component. As compared to the N-terminal sequences of the known PLA2s, both AP-PLA2-I and II were identified as class I enzymes not only because they have Cys-11 and lack Cys-51 but also because they contain the elapid loop in the region 53-61.

Amino Acid Sequence↗

PubMed1998

Tigloylcholine: a new choline ester toxin from the hypobranchial gland of two species of muricid gastropods (Thais clavigera and Thais bronni).

Crude extracts from hypobranchial glands of two species of muricid gastropods, Thais clavigera and Thais bronni, were highly lethal to mice. Regardless of species, a new choline ester was isolated as the major toxic principle and elucidated to be tigloylcholine, a structural isomer of senecioylcholine widely found in gastropod hypobranchial glands, by 1H- and 13C-NMR as well as FAB-MS. The i.v. LD50 (mouse) of tigloylcholine was estimated to be 0.92 mg/kg.

Animals↗

PubMed1998

Use of a channel biosensor for the assay of paralytic shellfish toxins.

Gonyautoxin (GTX), saxitoxin (STX) and tetrodotoxin (TTX), also known as paralytic shellfish poisons (PSP), block Na+ channels, including those in the frog bladder membrane. A tissue biosensor has been developed, consisting of a Na+ electrode covered with a frog bladder membrane integrated within a flow cell. The direction of Na+ transfer, investigated in the absence of Na+ channel blockers, established that active transport of Na+ occurs across the frogs bladder membrane from the internal to the external face. Transfer was shown to be TTX sensitive. The tissue sensor response to each of the different PSP was recorded and the results compared with toxicities determined by the standard mouse bio-assay. Using high concentrations of TTX from the puffer fish Takifugu niphobles, a linear correlation was found between the results from the two assay systems. However, the tissue biosensor system was also able to detect very low concentrations of TTX in samples from two species of puffer fish (Takifugu niphobles and Takifugu pardalis) at concentrations below the detection limit of the mouse bio-assay.

Animals↗

PubMed1998

Segmental mediolytic arteritis [correction of arteries]: a case report with review of the literature.

Segmental mediolytic arteritis is a very rare vascular disease which causes sudden intraabdominal hemorrhage. The disease is characterized by degeneration of the arterial media, followed by aneurysmal dilatation and rupture of the involved artery. Up to now, only 13 cases have been reported, and this unique disease is not fully recognized among general pathologists and physicians. Here, we present a case of segmental mediolytic arteritis involving the propria hepatic artery, which resulted in intraabdominal hemorrhage, and consequently hypovolemic circulatory disturbance. Histologically, the rupture focus showed degeneration and desquamation of the intima and media with fibrin-like material covering the exposed adventitia. Inflammatory infiltrates were only noted in the rupture focus as a secondary reactive change. Other than the rupture focus, there were two foci showing similar findings. This disease has rarely been reported and is seldom recognized as a cause of arterial rupture. In cases of sudden intraabdominal hemorrhage, segmental mediolytic arteritis should be considered as a possible cause in addition to atherosclerotic and mycotic aneurysm, traumatic injury and vasculitis syndromes.

Adult↗

PubMed1998

Production of trypsins by human gastric cancer cells correlates with their malignant phenotype.

Proteolytic degradation of extracellular matrix is a critical step in tumour invasion and metastasis. To examine the role of trypsin in tumour dissemination, we cloned two variants (S4 and R3 cells) from STKM-1, a trypsinogen 1-producing diffuse gastric cancer cell line. Western blot analysis with antitrypsin antibody showed that 26 and 24 kDa proteins were highly detected in S4 conditioned medium (CM) in comparison to R3 CM. In addition to the 26 and 24 kDa proteins, 25 and 23 kDa bands, which correspond to enterokinase-activated trypsin, were found only in S4 CM. When the CMs of the two clones were treated with enterokinase, the 25 and 23 kDa trypsin activities in S4 CM were effectively increased as compared with R3 CM. When the two clones were inoculated intraperitoneally (i.p.) into nude mice, S4 cells strongly invaded the liver, pancreas and peritoneum and killed the hosts more rapidly than R3 cells: the 50% survival time was 50 days for S4 and 82 days for R3 cells. These results suggest that trypsin production is associated with the invasive growth of STKM-1 gastric cancer cells.

Animals↗

PubMed1998

Stimulation of cellular growth and adhesion to fibronectin and vitronectin in culture and tumorigenicity in nude mice by overexpression of trypsinogen in human gastric cancer cells.

It has previously been reported that the trypsinogen gene is expressed in various human cancers. To investigate the possible role of trypsin in tumor malignancy, trypsinogen-1 cDNA was introduced into the human gastric carcinoma cell line MKN-1. The overexpression of trypsinogen-1 in MKN-1 cells stimulated cellular growth and adhesion to fibronectin and vitronectin when the trypsinogen activator enterokinase was added into the culture. Enterokinase treatment of the conditioned medium of the MKN-1 transfectants partially converted the proforms of gelatinases B and A to their apparent active forms. When the MKN-1 transfectants expressing trypsinogen-1 were intraperitoneally transplanted into nude mice, the mice frequently produced tumors in the colon, spleen and liver. However, the mice implanted with control MKN-1 cells produced no tumors. These results strongly suggest that tumor-derived trypsin contributes to the disseminated growth of some types of cancer cells including gastric cancer.

Adenocarcinoma↗

PubMed1998

Pulmonary adenocarcinomas of the fetal lung type: a clinicopathologic study indicating differences in histology, epidemiology, and natural history of low-grade and high-grade forms.

Seven cases of high-grade adenocarcinoma of fetal lung type (H-FLAC) are compared with nine cases of pulmonary endodermal tumor resembling fetal lung or low-grade adenocarcinoma of fetal lung type (L-FLAC). Of the seven patients with of H-FLAC, four were men and three were women. All of the patients but one were in their 60s or 70s. Five patients were smokers. After resection of the tumor, three patients died of metastases, two patients are alive with no evidence of disease, and two patients died of a postoperative complication. Histologically, H-FLAC and L-FLAC have both complex glandular structures resembling fetal lung and neuroendocrine differentiation. Two cases of H-FLAC had stromal proliferation typical of biphasic pulmonary blastoma. The H-FLAC was distinguished from L-FLAC by the presence of disorganized glands, large vesicular nuclei, prominent nucleoli, pronounced anisonucleosis, absence of morules, transition to conventional adenocarcinoma, broad areas of necrosis, desmoplastic stroma, overexpression of p53 protein, and production of alpha-fetoprotein. High and low grades of FLAC explain discrepancies in previously reported clinicopathologic features of FLAC. The H-FLAC needs to be distinguished from L-FLAC. Both forms may have stromal components, so both have been referred to as blastomas. The H-FLAC represents the prototype of so-called pulmonary blastoma predominantly seen in the elderly, whereas L-FLAC and its biphasic form predominate in the middle-aged population.

Adenocarcinoma↗

PubMed1998

Inhibition by E-4031 of the prolongation of the first returning cycle length after overdrive in anesthetized dog hearts.

Prolongation of the functional recovery of the sinoatrial (SA) nodal pacemaker activity after overdrive, "overdrive suppression," is determined by intrinsic pacemaker activity, pacemaker site, and SA conduction. We investigated the effects of E-4031, a blocker of a rapid type of the delayed rectifier K+ current (Ikr) and stimulation of the intracardiac parasympathetic nerves to the SA nodal region (SAP) on the prolongation of the first returning cycle length (1st RCL) after overdrive in autonomically decentralized hearts of open-chest anesthetized dogs. Second and third RCLs also were measured. We determined SA node recovery time (SNRT) and corrected SNRT (CSNRT) after atrial pacing at rates of 120, 150, and 200% of the control rate for 1 min and also determined SA conduction time (SACT) by the constant-atrial-pacing method. E-4031 (0.1-3 micromol/kg i.v.) increased the sinus cycle length (SCL) and SNRT dose dependently. However, E-4031 decreased CSNRT when the pacing rate was low or the number of pacing stimuli was small, although the agent did not induce a significant change in CSNRT when sufficient pacing stimuli were applied. E-4031 decreased SACT dose dependently. After E-4031 treatment. we observed changes in atrial electrical configurations, suggesting the possibility of pacemaker shift. When SAP stimulation increased SCL, SNRT, CSNRT, and SACT, E-4031 selectively inhibited the prolongation of SCL by SAP stimulation but did not affect the prolongation of CSNRT or SACT. These results suggest that functional recovery of the SA nodal pacemaker activity after overdrive is regulated by Ikr at least in part and that Ikr inhibition attenuates prolongation of the SCL but not the 1st RCL induced by parasympathetic nerve activation in the heart in situ.

Anesthesia↗

PubMed1998

Wide distribution of laminin-5 gamma 2 chain in basement membranes of various human tissues.

Laminin 5 (LN5), a heterotrimer of laminin alpha 3. beta 3. and gamma 2 chains. is a laminin isoform which strongly promotes adhesion. migration. and scattering of cells through binding to integrins alpha 3 beta 1, alpha 6 beta 1 and alpha 6 beta 4. To get an insight into the physiological functions of LN5, we prepared a mouse monoclonal antibody to human laminin gamma 2 chain and used it for immunohistochemical analysis of laminin gamma 2 chain in normal human tissues. The basement membranes of various epithelial tissues, such as the skin, lung, small intestine, stomach, kidney and prostate, were immunostained with the anti-laminin gamma 2 chain monoclonal antibody. In addition, the basement membrane of the surface germinal epithelium in the ovary was also positive for laminin gamma 2 chain. These results suggest general roles of LN5 in the anchorage of various types of epithelial cells to the underlying basement membrane and in the expression of their cellular functions. Moreover, deposition of laminin gamma 2 chain around small arteries and veins was observed in the thymus and spleen. This lymphatic organ-specific expression of vascular LN5 might provide a novel function of LN5 in immune responses.

Adult↗

PubMed1998

Different chronotropic and inotropic effects of EMD 57033 and EMD 53998, Ca2+ sensitizers, on isolated, blood-perfused dog heart preparations.

To investigate whether a Ca2+ sensitizer increases sinus rate, we studied the effects of racemic thiadiazinone, EMD 53998 (a Ca2+ sensitizer with phosphodiesterase inhibitory action) and its (+)-enantiomer EMD 57033 (a relatively pure Ca2+ sensitizer) on isolated, blood-perfused spontaneously beating right atria and paced left ventricles of the dogs. EMD 53998 increased sinus rate dose-dependently, but EMD 57033 did not. Both substances increased atrial and ventricular contractile force. Propranolol did not affect the responses to each substance. These results suggest that the Ca2+ sensitizing action induced by EMD 57033 does not affect pacemaker currents directly.

Animals↗

PubMed1998

Purification and IgE-binding epitopes of a major allergen in the gastropod Turbo cornutus.

The major allergen (Tur c 1) in the muscle of the gastropod, Turbo cornutus, was isolated by Sephacryl S-300, Mono Q HR 5/5 and TSKgel Phenyl-5PW RP column chromatography. ELISA showed Tur c 1 to react strongly with sera from three individuals sensitive to both mollusks and crustaceans. SDS-PAGE showed Tur c 1 to produce a major band corresponding to a molecular mass of 35 kDa under the reduced condition. Its amino acid composition was characterized by the abundance of Glx, followed by Leu, Ala and Lys in decreasing abundance, and the absence of Trp. In addition to these properties, the determined partial amino acid sequence identified Tur c 1 to be a tropomyosin, as in the case of the known mollusk and crustacean allergens. However, the results of competitive ELISA inhibition experiments suggest that Tur c 1 has an IgE-binding epitope in the C-terminal region which is dissimilar to those proposed for Cra g 1 (the oyster Crassostrea gigas allergen) and Pen i 1 (the shrimp Penaeus indicus allergen).

Allergens↗

PubMed1998

[Nurses' knowledge of alcohol-related problems and their treatment: a comparison of nurses in general hospital and alcoholism treatment units].

Nurses have the most contact with patients in the clinical settings, and they play an important role in the guidance and education of patients. Nurses' basic knowledge of alcohol-related problems greatly influences early discovery of and early intervention against alcohol-related problems in general units (GU). In a study undertaken mainly to understand the status of nurses' knowledge in GU, a survey was performed to compare the knowledge and attitude of nurses working in GU and those with working in units specializing in the treatment of alcoholism (AU). For reference, we used the results of separate surveys performed previously on the general population. The results showed that, compared with nurses in AU, nurses in GU (1) were more tolerant of drinking, but (2) were more stigmatic concerning alcoholism, and (3) had little knowledge concerning alcohol-related problems. Nurses in GU tended to have less knowledge about alcohol-related problems than the general population. Moreover, the knowledge of nurses in AU could not be considered sufficient. This study suggested the need for basic education concerning alcohol-related problems and their treatment aimed at nurses.

Adult↗

PubMed1998

[A case of primary lung cancer presenting as pneumothorax].

A 62-year-old man presented pneumothorax as a first manifestation of lung cancer was described. The patient complained right side chest pain and dry cough of 6 days duration. On the day of admission, a chest radiograph showed a large pneumothorax on the right. After 3 days of tube drainage, the lung was re-expanded and a chest radiograph showed a mass density above the right hilum. A chest CT revealed a cavitating tumor of the right upper lobe with a fistula to the pleural space. Right upper lobectomy was performed, and the histology was squamous cell carcinoma. The cause of pneumothorax was bronchopleural fistula secondary to rapid growth of the cancer. Pneumothorax due to primary lung cancer is rare and the prognosis is poor because the cancer was advanced stage or diagnosis of cancer was delayed in the literature review. Lung cancer should always be considered as a possible cause of pneumothorax, and it is important to diagnose lung cancer as soon as possible.

Carcinoma, Squamous Cell↗

PubMed1998

[An operative case of primitive neuroectodermal tumor in the posterior mediastinum].

A primitive neuroectodermal tumor (PNET) is very rare and the prognosis of this tumor is poor. A 32-year-old woman complaining of dysphagia and back pain was admitted to our hospital for the posterior mediastinal tumor. The tumor originated from the muscle layer of esophagus and en bloc resection of the tumor combined with the affected part of esophagus was performed. Histopathological diagnosis of the resected tumor was PNET. She received adjuvant chemotherapy. Eight months after the surgery, recurrent tumors in the right mediastinum and the retrooperitoneal space was resected completely. But after the second surgery, dissemination occurred recurrently. These recurrent tumors revealed high sensitivity for radio-therapy. However, she died of rapid recurrence 22 months after the first surgery. In Japan, our case is the second case of PNET in the posterior mediastinum and the first case of PNET arising from the muscle layer of esophagus.

Adult↗