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M Nagasaki

Publications and source records attributed to M Nagasaki.

At least 37 records · Page 2Linked to original sources

Clinical significance of mdm2 and p53 expression in bladder cancer. A comparison with cell proliferation and apoptosis.

BACKGROUND: Clinical significance of immunohistochemically detectable level of p53 protein has been reported, but with some limitation as a prognosticator of bladder cancer patients. Whether or not simultaneous evaluation of mdm2 and p53 expression in bladder cancer exceed the prognostic significance of conventional histological findings, cell proliferation markers and apoptotic parameters remains unclear. MATERIALS AND METHODS: The paraffin-embedded materials taken from 84 patients with transitional cell carcinoma of the bladder who were treated with total cystectomy were used in this study. Immunostainings of p53 protein, mdm2 protein and Ki67 antigen were performed using monoclonal antibodies (clone DO7, clone 1B10 and clone MIB1, respectively). In addition, the apoptotic cells were determined using a terminal deoxynucleotidyl transferase (TdT) mediated dUTP biotin nick end labeling (TUNEL) technique. The results were quantitatively evaluated using a CAS 200 Image Analyzer (Cell Analysis System, Elmhurst, Ill., USA) and were compared with histological findings and clinical course. RESULTS: The mean values of mdm2 expression, p53 immunoreactivity, Ki67 expression and apoptotic index were 19.2, 20.5, 22.4 and 0.96%, respectively. Histological grade and pT category were significantly positively correlated with 53 immunoreactivity (p < 0.05 and p < 0.05, respectively), Ki67 expression (p < 0.005 and p < 0.0001, respectively) and apoptotic index (p < 0.01 and p < 0.0001, respectively), while both were not correlated with mdm2 expression. Using univariate analysis, the prognostic relevance for both survival and disease progression was noted in histological grade, pT category, p53 expression, Ki67 index and apoptotic index, whereas it was not in mdm2 expression. However, when analyzing the simultaneous evaluation of mdm2 and p53 expression (mdm2-p53 category), the relationship of the mdm2-p53 category with Ki67 expression and apoptotic index showed a statistical significance and a borderline significance (p = 0.0085 and p = 0.0652, respectively). In addition, the patients with both mdm2(-) and p53(-) showed a significant better prognosis as compared with either counterpart of mdm2-p53 category (p < 0.05 for both). Multivariate analysis revealed only pT category and mdm2-p53 category as independent factors for both disease progression and survival. CONCLUSIONS: Clinical significance of simultaneous evaluation of mdm2 and p53 immunostaining proved to be superior over that of cell proliferation and/or apoptotic markers when elucidating the biological characteristics of bladder cancer.

Adult↗

[Primary Sjögren's syndrome presenting as unconsciousness associated with IgA-lambda M-protein].

We describe the case of a 43-year-old woman who presented with primary Sjögren's syndrome (SS) which manifestated as unconsciousness due to M protein. A diagnosis of SS was made based on a ten-year history of dryness, a Shirmer test, and the histological findings of labial biopsy. A rouleaux formation was observed and serum protein electrophoresis revealed a monoclonal spike of 4.0 gm/dl in the gamma-region, which was characterized as IgA-lambda. Biopsy of the minor salivary glands showed marked polyclonal lymphoproliferation with lymphoid follicles, including both T cells and B cells as revealed by immunohistological staining. Therefore, the patient had a lymphoproliferative lesion of the minor salivary glands, which is also known as pseudolymphoma. We conclude that fainting associated with marked M protein may be manifestation of SS. Such cases should be followed carefully since the subsequent neoplastic transformation of pseudolymphomas have been previously reported.

Female↗

[Pharmacokinetic analysis of cefozopran in neonatal infections--population pharmacokinetics using nonmem].

This report describes the results on pharmacokinetics, efficacy and safety of cefozopran (CZOP) in neonatal patients. Enrolled patients were 136 in total whose informed consents to enter this study had been given by their parents. Among them, blood samples were collected from 42 neonates to analyze concentrations of CZOP by population pharmacokinetics (PPK) methods. Based on this analysis, the average pharmacokinetic parameters of CZOP and the variabilities of them in different morbid pharmacological backgrounds and in different subjects were evaluated. This PPK analysis showed that clearance (CL) and distribution volume (Vd) of CZOP could be estimated by the following equations; CL = 0.0452 x WT1.75 (in the case of the postnatal age of over than 1 day) CL = 0.623 x 0.0452 WT1.75 (in the case of the postnatal age of 1 day or less) Vd = 0.455 x WT where WT indicates body weight in kg. The coefficients of variation among individual subjects on CL and Vd were found to be 20.7% and 20.0%, respectively. From this PPK analysis it was indicated that the elimination of CZOP is dependent on the postnatal age and is approximately 38% lower in the younger group than in the older group. Therefore, it could be concluded that, though the cases of evaluation were small in number, adjustment of dosing of CZOP is necessary, particularly in prolongation of intervals of administration, in cases of postnatal age of 1 day or less.

Cephalosporins↗

Bio-calculus: Its Concept and Molecular Interaction.

The way for expressing biological systems is a key element of usability. Expressions used in the biological society and those in the computer science society have their own merits. But they are too different for one society to utilize the expressions of the other society. In this paper, we design the bio-calculus that attempts to bridge this gap. We provide syntax which is similar to conventional expressions in biology and at the same time specifies information needed for simulation analysis. The information and mathematical background of bio-calculus is what is desired for the field of computer science. We show the practicality of bio-calculus by describing and simulating some molecular interactions with bio-calculus.

Journal Article↗

Sarcoidosis associated with multiple large pulmonary nodules.

Parenchymal manifestations of pulmonary sarcoidosis include a diffuse, symmetric, reticulonodular interstitial pattern, a fibrotic pattern, and an acinar pattern. Large pulmonary nodules in sarcoidosis are rare, and their frequency (> 1 cm in diameter) has been estimated at 2-4%. We report a rare case of sarcoidosis associated with large bilateral pulmonary nodules. These nodules reached up to 7 cm in diameter, which is larger than any others reported previously. Furthermore, these nodular lesions developed within only 6 months of normal chest X-ray results and were not found to accompany bilateral hilar lymph adenopathy, which is observed in the usual course of sarcoidosis. As described above, this case of pulmonary sarcoidosis was significant not only in terms of the large size of the nodules but also the unique chest X-ray course.

Adult↗

Gastric mucosal function following withdrawal of omeprazole in rats.

In the following study the function of gastric mucosa after withdrawal of 4-week suppression of acid secretion was examined. Rats were treated orally for 4 weeks with omeprazole (CAS 73590-58-6, 150 mg/kg/day). While elevated plasma gastrin levels during the treatment returned to normal 4 days after the last dosing, exogenously applied pentagastrin induced higher acid secretion compared with the vehicle-treated controls. Acetylsalicylic acid induced mucosal lesion 3.6-fold over the control as well. In contrast, the HCl-induced lesion was inhibited by 24.4%. These results indicate that not only the acid secretion but also the mucosal protection is enhanced after 4-week treatment with omeprazole in rats.

Analgesics, Non-Narcotic↗

Immunohistochemical analysis of estramustine binding protein with particular reference to proliferative activity in human prostatic carcinoma.

BACKGROUND: The estramustine binding protein (EMBP) specifically binds to estramustine and was first discovered in the rat ventral prostate. However, the physiological property of EMBP in the human prostate still remains to be elucidated. To elucidate whether EMBP is interrelated with cellular proliferation in human prostatic carcinoma (PC), the change in EMBP immunostaining during luteinizing hormone-releasing hormone (LH-RH) analog administration or during Cis-platinum-based chemotherapy, and the difference in EMBP immunostaining between hormone refractory (hr-PC) and untreated PC were analyzed. METHODS: Forty-six patients with histologically proven untreated PCs (34 were treated with LH-RH analog and 12 were treated with chemotherapy as an initial therapy) and 14 with hr-PC were used in this study. PC tissues were obtained before and 3 months after the initial therapy. The changes in immunostainings for EMBP, proliferating cell nuclear antigen (PCNA), and nm23 protein were compared with the change in serum prostate-specific antigen (PSA) level and the histological response during the treatment. RESULTS: The increased EMBP expression was observed in tumors with high histological grade and high clinical stage as well as in hr-PC. In untreated PC, EMBP expression weakly correlated with PCNA or nm23 protein immunoreactivity. In PC receiving LH-RH analog, EMBP expression was significantly reduced after treatment, however, no significant changes were observed in PCNA or nm23 protein immunoreactivity. In addition, EMBP expression before the treatment significantly correlated with the serum PSA change, while PCNA expression and nm23 protein immunoreactivity did not. On the other hand, no significant relationship was observed between histological changes induced by the LH-RH analog and immunostainings for EMBP, PCNA, and nm23 protein before treatment. In PC patients receiving chemotherapy, immunostainings for EMBP, PCNA, and nm23 protein were not significantly changed during the treatment. EMBP immunoreactivity was significantly higher in hr-PC than in untreated PC with paralleled change of PCNA expression and nm23 protein immunoreactivity. CONCLUSIONS: These observations indicate that EMBP is androgen regulated in some PCs. However, EMBP expression is demonstrated even in hr-PC and is interrelated with cellular proliferation especially in hr-PC.

Aged↗

Role of vagus nerves and gastrin in the gastric phase of acid secretion in male anesthetized rats.

We used the pylorus ligation model to determine the role of vagus nerves and gastrin in acid secretion induced by mechanical and chemical stimulation of the gastric lumen in anesthetized male rats. Gastric distension induced by intragastric instillation of saline resulted in a 17-fold increase in acid secretion over the basal level without an alteration in serum gastrin levels. Distension-stimulated acid secretion was inhibited by bilateral subdiaphragmatic vagotomy but not by CI-988, a gastrin receptor antagonist. Intragastric peptone produced a 71-fold increase in acid secretion over the basal level that was accompanied by a significant increase in serum gastrin levels. Whereas vagotomy almost abolished peptone-stimulated acid secretion, CI-988 inhibited peptone-stimulated acid secretion by only 50%. We conclude that the vagus nerves mediate acid secretion by mechanical and chemical stimulation and that gastrin mediates acid secretion partly by chemical stimulation but not by mechanical stimulation in anesthetized male rats.

Animals↗

Solid and cystic tumor (SCT) of the pancreas in an adult man.

Solid and cystic tumor (SCT) of the pancreas predominantly occurs in women, and the occurrence in men is extremely rare. We experienced a male case of SCT. A 38-year-old man was admitted with the complaint of upper abdominal pain. CT scan showed the presence of a mass in the head of the pancreas. The mass was composed of high density areas and low density areas. Ultrasonograms revealed the mass being composed of high echoic areas and low echoic areas. The mass was hypovascular on angiography. SCT was suspected and pancreaticoduodenectomy was performed. The cut surface of the tumor showed mainly cystic degenerative areas containing dark red hemorrhagic materials. Microscopically, there were solid areas in the periphery and pseudopapillary areas in the center. No metastasis was found in the removed lymph nodes. The tumor cells were not stained by Grimelius' silver stain. The tumor cells were positive for alpha-1-antitrypsin (AAT) and neuron-specific enolase (NSE). Pancreatic hormones such as insulin, glucagon, and somatostatin were all negative. Electron micrograph showed that tumor cells were rich in mitochondria. Zymogen granules and neurosecretory granules were not detected. Estrogen receptor (ER) and progesterone receptor (PR) were both negative.

Adult↗

Effect of T-0632, a cholecystokininA receptor antagonist, on experimental acute pancreatitis.

Effects of a new cholecystokinin (CCK)A-receptor antagonist, T-0632 [sodium (S)-1-(2-fluorophenyl)-2, 3-dihydro-3-[(3-isoquinolinylcarbonyl) amino]-6-methoxy-2-oxo-1H-indole-3-propanoate], on caerulein-induced and pancreatic duct ligation-induced pancreatitis models were studied and compared with the CCKA-receptor antagonist loxiglumide and the orally active protease inhibitor camostate, respectively. In rats, orally administered T-0632 potently prevented the caerulein-induced increases in pancreatic digestive enzymes in plasma and suppressed the histological changes in the pancreas. The estimated ED50 values of T-0632 and loxiglumide were 0.0092 and 8.9 mg/kg, respectively. In dogs, T-0632 (0.1, 1 mg/kg, i.d.) prevented the caerulein-induced increase in plasma amylase activity in a dose-dependent manner. Loxiglumide (100 mg/kg, i.d.) did not show any preventive effects. In pancreatic duct ligation (6 hr)-induced pancreatitis of the rat, T-0632 (0.001-0.1 mg/kg, p.o.) partially prevented both the increase in plasma amylase activity and the histological changes in the pancreas, whereas camostate (10, 100 mg/kg, p.o.) did not show any preventive effects. In pancreatic duct ligation (3 hr)-induced pancreatitis, caerulein injection (1 microgram/kg, s.c.) caused a further increase in plasma amylase activity, and T-0632 (0.01, 0.1 mg/kg, p.o.) dose-dependently decreased the aggravation by caerulein. We conclude that T-0632 showed preventive effects on all of these pancreatitis models by oral or intraduodenal administration. These results suggest that CCK plays an important role in progression and aggravation of acute pancreatitis, and T-0632 may have a therapeutic value in these disease states.

Acute Disease↗

Pharmacological profile of T-0632, a novel potent and selective CCKA receptor antagonist, in vivo.

The pharmacological profile of a new CCKA receptor antagonist, T-0632 [sodium (S)-1-(2-fluorophenyl)-2,3-dihydro-3-[(3-isoquinolinylcarbonyl) amino]-6-methoxy-2-oxo-1H-indole-3-propanoate], was examined in in vivo studies and compared with those of L-364, 718 [3S(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1, 4-benzodiazepine-3-yl)-1 H-indole-2-carboxamide] and loxiglumide [D.L-4-(3,4-dichlorobenzoylamino)-5-(N-3-methoxypropyl-pentylam ino)-5- oxopentanoic acid]. In rats, intravenously administered T-0632, L-364,718 and loxiglumide dose dependently inhibited cholecystokinin octapeptide (CCK-8)-stimulated pancreatic exocrine secretion with estimated ED50 values of 0.025, 0.016 and 1.8 mg/kg, respectively. The ED50 values for intraduodenal administration of these compounds were 0.040, 0.26 and 3.0 mg/kg, respectively. In mice, orally administered T-0632 prevented caerulein-induced pancreatitis, CCK-8-induced inhibition of gastric emptying and CCK-8-induced gallbladder emptying in dose-dependent manners with ED50 values of 0.028, 0.04, and 0.12 mg/kg, respectively. The effect of T-0632 for caerulein-induced pancreatitis was 4-fold more potent than that for gallbladder emptying. In contrast, the effects of L-364,718 and loxiglumide for caerulein-induced pancreatitis were 2-4-fold weaker than those for gallbladder emptying. In dogs, T-0632 and loxiglumide maximally inhibited CCK-8-stimulated pancreatic amylase secretion at doses of 0.01 and 10 mg/kg, respectively. At these doses, the effect of T-0632 on CCK-8-induced increase in the gallbladder intraluminal pressure was weaker than that of loxiglumide. These results suggest that T-0632 has a potent antagonistic action on CCKA receptors in several animal species and the effects of T-0632 are more selective for the pancreas over the gallbladder compared with L-364,718 and loxiglumide.

Animals↗

Pharmacological profile of T-0632, a novel potent and selective CCKA receptor antagonist, in vitro.

The pharmacological profile of a new CCKA receptor antagonist, T-0632 [sodium (S)-3-[1-(2-fluorophenyl)-2,3-dihydro-3-[(3-isoquinolinyl)-carbonyl] amino-6-methoxy-2-oxo-1-H-indole]propanoate], was examined in in vitro studies and compared with those of L-364,718 [3S(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1, 4-benzodiazepine-3-yl)-1H-indole-2-carboxamide] and loxiglumide [D,L-4-(3,4-dichlorobenzoylamino)-5-(N-3-methoxypropyl-pentylam ino)-5- oxopentanoic acid]. T-0632 inhibited the specific binding of [125I]CCK-8 to rat pancreatic CCKA receptor in a concentration-dependent and competitive manner. The Ki value of T-0632 for the CCKA receptor was estimated to be 0.24 nM, which was 23 000-fold less than the Ki value (5600 nM) for guinea pig CCKB receptor. L-364,718 and loxiglumide were 1500- and 64-fold selective for CCKA over CCKB receptor, respectively. T-0632, L-364,718 and loxiglumide inhibited CCK-8 (100 pM)-stimulated amylase release from rat pancreatic acini in a concentration-dependent manner with IC50 values of 5.0 nM, 5.0 nM and 3.0 microM, respectively. In the isolated rabbit gallbladder smooth muscle, T-0632 and loxiglumide competitively inhibited CCK-8-induced contraction with pA2 values of 8.5 and 7.0, respectively. However, L-364,718 showed an apparent non-competitive antagonism. The IC50 values of T-0632, L-364,718 and loxiglumide for CCK-8 (30 nM)-induced contraction were 31 nM, 4.9 nM and 1300 nM, respectively. The inhibitory effects of T-0632 and loxiglumide in gallbladder smooth muscle were readily reversible, but L-364,718 showed a long-lasting inhibition. These results suggest that T-0632 is a potent, reversible and more selective CCKA receptor antagonist compared with L-364,718 and loxiglumide.

Amylases↗

Constitutive expression of granulocyte-colony stimulating factor receptor on a human B-lymphoblastoid cell line.

The present study demonstrated that a human B-cell line derived from non-Hodgkin's lymphoma. HCF-MLpN. constitutively expressed G-CSF receptor on the cell surface. G-CSF binding to the cell surface was shown by immunofluorescence staining using biotinylated G-CSF preparation and analysed by flow cytometry. Specific binding of G-CSF to the cells was shown by pretreatment with unlabelled G-CSF. In the radioreceptor assay and Scatchard plot analysis using radiolabelled ligand, MLpN cells revealed a single species of binding site with an equilibrium dissociation constant of 167 (153-182) pM and a maximal binding site per cell of 1076 (1044-1116). The G-CSF receptor mRNA transcript was exhibited in the RNA from MLpN cells by reverse transcriptase polymerase chain reaction procedure. [3H]thymidine incorporation and trypan blue exclusion showed that the G-CSF receptor was capable of transducing the growth signal to HCF-MLpN cells. A small fraction of fresh B blasts from six patients with B-cell lymphoma and leukaemia displayed G-CSF binding by two-colour immunofluorescence staining. In contrast, a panel of seven B-cell lines was negative for the binding to biotinylated G-CSF preparation. These results suggest that the phenotype of G-CSF binding may be lost during the culture. The expression of G-CSF receptor in HCF-MLpN cells appeared to be exceptional.

B-Lymphocytes↗

A new monoclonal antibody (IE8) reactive with dendritically shaped cells in the human tonsil.

A new monoclonal antibody (mAb), 1E8 (IgG1, kappa), was obtained from a hybridoma prepared by fusion of mouse myeloma cells (NS-1) with splenic cells of mice immunized with a human B blastic malignant lymphoma cell line, HPE-Ret-3 (Ret-3). The mAb showed a reactivity unrestricted to a specific cell lineage on flow cytometrical analysis of the reactivity with human lympho-hematopoietic cell lines. In peripheral blood, 1E8 reacted with the cells of all lineage, that is, lymphocytes, monocytes, granulocytes and platelets, even though its intensity was very low by immunohistochemistry. Immunohistochemical examination of human tonsil with 1E8 showed a characteristic staining pattern. Positive cells scattered in follicular (mantle zone and germinal center), parafollicular (T-dependent area), subepithelial and interstitial connective tissue areas. These positive cells seemed to be categorized into dendritically shaped cells (DSC), including dendritic cells (DC) and a subpopulation of macrophages in follicles, interdigitating cells (IDC) and irregularly shaped mononuclear cells. The localization of 1E8 antigen staining was similar to that of integrin CD11c, although its distribution on hematopoietic cell lines did not coincide with that of 1E8 antigen. Immunobiochemical studies showed that 1E8 bound two cell surface proteins with molecular size of 70,000-90,000 and 35,000 Da each. Consequently, 1E8 antigen might be a novel marker of DSC.

Animals↗

Effects of cholecystokinin (CCK)-JMV-180 on the CCK receptors of rabbit pancreatic acini and gallbladder smooth muscle.

Effects of cholecystokinin (CCK)-JMV-180, a CCK analog, on the CCK receptor functions of isolated rabbit pancreatic acini and gallbladder smooth muscle were studied. When the pancreatic acini were incubated with increasing concentrations of CCK-8, stimulation of amylase release reached a maximum at 3 nM and then declined with the increasing concentration of CCK-8. CCK-JMV-180 also caused a dose-dependent amylase release stimulation, which plateaued and remained unchanged above 300 nM at about 50% of the maximal stimulation by CCK-8. CCK-JMV-180 above 100 nM caused a rightward shift of the downstroke of the dose-response curve for CCK-8 (pA2 = 7.5). In the gallbladder smooth muscle, CCK-8 caused a dose-dependent contraction, but CCK-JMV-180 totally lacked this property. Instead, CCK-JMV-180 caused a rightward shift of the dose-response curve for CCK-8 (pA2 = 7.9). These results suggest that CCK-JMV-180 distinguishes between the CCKA receptors associated with pancreatic exocrine secretion in the acini and those involved in contraction of the isolated gallbladder smooth muscle in rabbits.

Amylases↗

An autopsy case of acquired immune deficiency syndrome (AIDS) with preceding aplastic anemia.

A case of acquired immunodeficiency syndrome (AIDS) with preceding aplastic anemia is reported. The patient was a 36 year old female who had been diagnosed as having aplastic anemia 10 years before and thereafter had received multiple transfusions. Human immunodeficiency virus (HIV)-seropositivity was revealed 10 months prior to her death, but no particular clinical signs indicating HIV infection, pre-AIDS or onset of AIDS were recognized before serological diagnosis, although the slow progression of leukopenia was noted along with thrombocytopenia. Her general condition deteriorated during the last 10 months accompanied by an acute decrease in the CD4/CD8 ratio. Autopsy revealed full-blown AIDS: systemic aspergillosis, progressive multifocal leukoencephalopathy, Epstein-Barr virus-related B cell lymphoma arising in the diaphragm and severe lymphocyte depletion in the lymph nodes and spleen. Markedly hypoplastic bone marrow was considered to be primarily attributable to the aplastic anemia but the affection of AIDS was not excluded. The possible transmission route of HIV and the effect of the preceding aplastic anemia on the infection and clinical course of AIDS are discussed.

AIDS-Related Opportunistic Infections↗

Effect of trimebutine on contractile responses in skinned ileal smooth muscle.

The effects of trimebutine on Ca2+ release and modulation of Ca2+ sensitivity of contractile elements induced by carbachol (CCh) were investigated using a tension measuring method in beta-escin-treated skinned smooth muscle of the longitudinal muscle layer of guinea pig ileum. Trimebutine (10-100 microM) concentration-dependently inhibited tension development brought about by Ca2+ release from intracellular stores induced by CCh (10 microM), but did not affect those induced by inositol 1,4,5-trisphosphate (IP3, 25 microM) or caffeine (5 mM). The inhibitory effect was reversible. Trimebutine (100 microM) neither altered the Ca2+ sensitivity of the contractile elements nor affected the effects of GTP gamma S (50 microM) and CCh (100 microM) in potentiating Ca2+ sensitivity of the contractile elements after the Ca2+ storage function had been eliminated by A23187. These results suggest that trimebutine inhibits CCh-induced Ca2+ release by acting at some point during the coupling of muscarinic receptors through a G-protein to phospholipase C and thus reducing the accumulation of IP3.

Animals↗

Effect of trimebutine on K+ current in rabbit ileal smooth muscle cells.

The effect of trimebutine on the K+ current in rabbit ileal smooth muscle cells was investigated using the whole-cell patch-clamp technique. Trimebutine (10 microM) inhibited an outward current consisting of a Ca(2+)-dependent K+ current (IKCa) and Ca(2+)-independent K+ current (IKv), elicited by stepping from -80 to -20 mV or more positive. Trimebutine reduced dose dependently the IKv amplitude with an IC50 of 7.6 microM and IKCa amplitude with an IC50 of 23.5 microM. The IKv inhibition was neither voltage- nor use-dependent. Trimebutine (1-100 microM) decreased the amplitude and discharge rate of spontaneous transient outward currents. Trimebutine (30 microM) produced a sustained membrane depolarization of about 10 mV accompanied by a decrease in membrane conductance. The results suggest that the excitatory effects of trimebutine on the gastrointestinal tract may be attributable to the inhibitory action on the K+ current.

Animals↗