Biomedical subjects

M Sawada

Publications and source records attributed to M Sawada.

At least 271 records · Page 15Linked to original sources

PubMed1994

Symptomatic middle cerebral artery stenosis and occlusion: comparison of three-dimensional time-of-flight magnetic resonance angiography with conventional angiography.

The usefulness of magnetic resonance (MR) angiography using the three-dimensional time-of-flight method for the characterization of symptomatic middle cerebral artery (MCA) occlusive lesions was evaluated in 10 patients with MCA occlusion and 10 with MCA stenosis. All lesions were symptomatic and documented by conventional angiography. There was no false-negative MR angiogram that failed to demonstrate the MCA occlusive lesion. MR angiography correctly evaluated the location of lesions and the difference between stenosis and occlusion. Stenosis appeared as a focal signal loss (< 1.0 cm) of the MCA at the site of stenosis, and occlusion as a complete signal loss of the MCA distal to the site of occlusion. However, MR angiography could not distinguish diffuse stenosis and one point stenosis demonstrated by conventional angiography. MR angiography is a useful noninvasive diagnostic method for evaluating occlusive lesions of the MCA in symptomatic patients.

Adult↗

PubMed1994

[Metastasis of an adenocarcinoma of unknown origin to mediastinal lymph nodes, and transient regression].

A 67-year-old woman was admitted to our hospital because of fever. Chest roentgenogram showed an enlargement of mediastinal lymph nodes. Despite thorough examination, no definite diagnosis could be made. The mediastinal lymph nodes got smaller over the next 3 weeks and a chest roentgenogram taken 4 months later showed no mediastinal lymphadenopathy. The mediastinal lymphadenopathy and fever recurred 5 months later. She underwent thoracotomy and the mediastinal lymph nodes were excised. Microscopic examination of pretracheal lymph node specimens showed invasion of poorly differentiated adenocarcinoma associated with abundant tumor-infiltrating lymphocytes. The other lymph nodes showed sarcoid reaction. Although she has been followed for one year and 11 months, no primary site of the cancer has been found. Metastasis of cancer of unknown origin to mediastinal lymph nodes is extremely rare. It is also interesting that the lymph node swelling diminished spontaneously. The tumor-infiltrating lymphocytes and sarcoid reactions may have been immunological responses to the cancer and may have caused the transient regression.

Adenocarcinoma↗

PubMed1994

[Qualitative evaluation of 123I-IMP SPECT using a rotating gamma camera in atherosclerotic large-artery disease].

PURPOSE Quantitative measurement of regional cerebral blood flow (rCBF) needs special equipment or invasive blood sampling. Therefore, with a popularly used rotating gamma camera, we tried to establish a convenient modality of qualitative evaluation of hemodynamics in patients with atherosclerotic large-artery disease, according to the distribution pattern of isotope-uptake on SPECT image. PATIENTS AND METHODS Forty-one patients with atherosclerotic large-artery disease [9 internal carotid artery (ICA) stenosis, 17 ICA occlusion, 8 middle cerebral artery (MCA) stenosis, and 7 MCA occlusion] and 32 control patients documented as having small cerebral infarction without atherosclerotic large-artery disease were investigated. Using the rotating gamma camera, they underwent 123I-IMP SPECT at baseline and after acetazolamide loading. According to the distribution pattern of low isotope-uptake, early images were classified into four types: Type I: no low uptake, Type II: low uptake in a single watershed, Type III: low uptake in two watersheds with or without a partial MCA territory, Type IV: low uptake in a whole MCA territory. RESULT In patients with large-artery disease, baseline images presented Type I in 12 cases, Type II in 16, Type III in 9, Type IV in 4, and loading images Type I in 3, Type II in 2, Type III in 8, Type IV in 28. Of 37 patients except for 4 belonging to Type IV at baseline, 32 (86.5%) had a more extensive low isotope-uptake area after acetazolamide loading than at baseline. In control patients, baseline images presented Type I in 25, Type II in 7, and the Type III & IV in 0, and the Type after loading was the same as the Type at baseline. CONCLUSION We established the qualitative evaluation of 123I-IMP SPECT image by detecting the "extent" of the ischemic region, taking notice of watershed. The pathognomonic findings on SPECT image of atherosclerotic large-artery disease showed that low isotope-uptake area at baseline extended into two watersheds or MCA territory by acetazolamide loading. The modality of qualitative evaluation based on these pathognomic findings of SPECT image may be useful for easily assessing patients with atherosclerotic large-artery disease using a rotating gamma camera.

Adult↗

PubMed1994

[The beneficial effects of PGI2 analogue (OP-41483-alpha-CD) on hepatic dysfunction after warm ischemic damage].

The purpose of the experimental study was to investigate the beneficial effects of aPGI2 analogue (OP-41483-alpha-CD; aPGI2) on hepatic dysfunction after warm ischemia and reperfusion. Hepatic warm ischemia was produced by temporary clamping of the portal vein and hepatic artery. Experimental groups were divided into three groups: Group I; 60-minutes ischemia, Group II; 90-minutes ischemia, Group III; 90-minutes ischemia with intravenous aPGI2 (0.25 microgram/kg/min) infusion. The results were as follows: 1; In groups I and III, hepatic tissue flow showed a marked increase after reperfusion when compared to Group II. 2; Arterial ketone body ratio in Groups I and III recovered significantly faster than those of Group II. 3; The tissue total adenine-nucleotide levels in Groups I and III were significantly higher than those of Group II. 4; In the comparison of the radical intensity which was measured by ESR spectroscopy, the free radical of the hepatic venous blood was markedly generalized after reperfusion in Group II. However, production of free radical has significantly suppressed in Group III when compared to Group II. These results suggest that aPGI2-treatment might improved the ischemic damaged liver and might improve the prognosis of the transplanted patient.

Alanine Transaminase↗

PubMed1994

An experimental model for ovarian tumor invasion of cultured mesothelial cell monolayer.

BACKGROUND: Peritoneal spread of tumor cells is one of the characteristic features of biologic behavior of ovarian cancers. To understand the mechanism by which human tumor cell invasion takes place, we have tried to establish an in vitro experimental model for ovarian tumor cell invasion of the mesothelial cell monolayer. EXPERIMENTAL DESIGN: Mesothelial cells were isolated from normal rat mesentery by trypsin digestion and the cells (1 x 10(5)/dish) were cultured in Eagle's minimum essential medium supplemented with 10% fetal calf serum. Cultured mesothelial cells (M cells) grew forming a pavement-like monolayer. When M cells grew to a confluent state, tumor cells (1 x 10(5)/dish) were seeded on M cell monolayers and cultured. Four tumor cell lines derived from human ovarian cancers were tested for their invasive behaviors. The penetration of M cell monolayers by the tumor cells was confirmed by a perpendicular section of the cell layers. The number of penetrated single tumor cells and colonies/cm2 was counted under a phase contrast microscope after the tumor cell seeding. RESULTS: Several hours after the tumor cell seeding, the cells adhered to M cell monolayers and started to penetrate by extending pseudopodia-like cytoplasmic processes through junctional margins of neighboring M cells, resulting in the formation of penetrated single tumor cells that then proliferated to form colonies under the monolayer. The number of penetrated single tumor cells and colonies/cm2 increased up to 24 hours after the tumor cell seeding, and thereafter stayed almost constant. The number increased with the number of tumor cells seeded, when counted at 48 hours, and therefore was taken to be the number of tumor cells invaded. The in vitro invasiveness of tumor cells varied with the tumor cell lines examined. CONCLUSIONS: Application of this system appears to provide rapid determinations of the invasive potential of ovarian tumor cells and to make it easy to screen substances that modify the invasion of mesothelial cells.

Adenocarcinoma↗

PubMed1994

[A case of crescentic glomerulonephritis associated with anti-myeloperoxidase antibody presenting as alveolar hemorrhage].

A 77-year-old man was admitted because of hemoptysis. Chest roentgenograms initially showed progressive infiltrative shadows, which improved spontaneously in 3 months. Transbronchial lung biopsy specimens obtained during the first admission revealed alveolar hemorrhage with neither granuloma nor vasculitis. Alveolar hemorrhage associated with renal dysfunction recurred 9 months later. Serum creatinine level was elevated to 3.5 mg/dl. No other organ than lungs or kidneys was involved. Renal biopsy was performed to confirm the pathological diagnosis of crescentic glomerulonephritis. Anti-basement-membrane antibody was negative, whereas anti-neutrophil-cytoplasmic antibody was positive for perinuclear pattern (P-ANCA) by indirect immunofluorescent (IF) method. He was diagnosed as having idiopathic crescentic glomerulonephritis complicated with alveolar hemorrhage, and the presence of anti-myeloperoxidase (MPO) antibody in serum was anticipated. Anti-MPO antibody level in his serum evaluated by ELISA was markedly elevated. Although myeloperoxidase has been considered as a common antigen to P-ANCA and anti-MPO antibody, the determination of P-ANCA has been clinically unreliable because of equivocal results. In contrast, the presence of anti-MPO antibody is highly specific for idiopathic crescentic glomerulonephritis complicated with alveolar hemorrhage or its incomplete variant case. Also, it is a better index of disease activity. Therefore, there is a possibility that those patients diagnosed as having idiopathic pulmonary hemosiderosis or pulmonary-renal syndrome may be categorized into the one disease, anti-MPO antibody-associated disease, and the measurement of anti-MPO antibody may lead to prompt treatment prior to the histological diagnosis.

Aged↗

PubMed1993

Expression of alpha-(1,3)-fucosyltransferases which synthesize sialyl Le(x) and sialyl Le(a), the carbohydrate ligands for E- and P-selectins,in human malignant cell lines.

Transcripts of alpha-(1,3)-fucosyltransferases in human epithelial cancer and leukemia cell lines were analyzed by Northern blotting and reverse transcriptase mediated-polymerase chain reaction using specific probes and primers which can discriminate between the transcripts derived from the four alpha-(1,3)-fucosyltransferase genes Fuc-TIII, IV, V, and VI. Flow cytometric analysis of the sialyl Le(x) and sialyl Le(a) antigens was also performed on the same cell lines. The sialyl Le(x) antigen was expressed on 14 of 15 epithelial cancer cell lines, and the sialyl Le(a) antigen was detected on 8 of them. The message of Fuc-TIII was detected in most of the epithelial cancer cell lines (14 of 15), which correlated with the surface expression of these carbohydrate determinants. In addition, the messages of Fuc-TIV and Fuc-TVI were detected in most epithelial cancer cell lines, while the message of Fuc-TV was undetectable in most of them. On the other hand, all leukemia cell lines were positively stained for sialyl Le(x), but none of them was stained for sialyl Le(a) in flow cytometry. The messages of Fuc-TIV++ were detected in all leukemia cell lines tested. Small quantities of Fuc-TIII, V, and/or VI messages were also detected in some leukemia cell lines in reverse transcriptase mediated-polymerase chain reaction analysis. These studies indicate that alpha-(1,3)-fucosyltransferase activities in epithelial cancer and leukemia cell lines are mixtures of multiple molecular species of alpha-(1,3)-fucosyltransferases. It is natural that epithelial cancer cells contain a significant amount of Fuc-TIII mRNA and leukemia cell lines contain Fuc-TIV mRNA, since their normal counterparts, normal epithelial cells and leukocytes, respectively, are known to contain these fucosyltransferases. The unexpectedly frequent occurrence of Fuc-TIV mRNA in epithelial cancer cell lines may be related to their retro-differentiation associated with tumorigenesis. Another unexpected finding was a weak but significant expression of the alpha-(1,3)-fucosyltransferases Fuc-TIII, V, and/or VI in leukemia cell lines detected by reverse transcriptase mediated-polymerase chain reaction analysis. Since these enzymes are known to be capable of synthesizing the sialyl Le(x) determinant, this finding implies a possibility that some of them may be involved in the synthesis of sialyl Le(x) in leukemia cells.

Adenocarcinoma↗

PubMed1993

Calcitonin induces a decreased Na+ conductance in identified neurons of Aplysia.

The ionic mechanism of the effect of extracellularly ejected calcitonin (CT) on the membrane of identified neurons R9 and R10 of Aplysia was investigated with voltage-clamp, micropressure ejection, and ion substitution techniques. Micropressure-ejected CT caused a marked hyperpolarization in the unclamped neuron. Heat-inactivated CT was without effect. Clamping the same neuron at its resting potential level (-60 mV) and re-ejecting CT with the same dose produced a slow outward current (Io(CT), 30-40 sec in duration, 4-6 nA in amplitude) associated with a decrease in input membrane conductance. Io(CT) was decreased by depolarization and increased by hyperpolarization. The extrapolated reversal potential of Io(CT) was approximately +10 mV. Io(CT) was sensitive to changes in the external Na+ concentration but not to changes in K+, Ca2+, and Cl- concentrations. Micropressure-ejected forskolin produced a slow outward current, which, like the current to CT, was associated with a decrease in input membrane conductance, and was sensitive to changes in the external Na+ concentration. Io(CT) was prolonged by bath-applied isobutylmethylxanthine (IBMX) but was not affected by 1-oleoyl-2-acetylglycerol (OAG) and calphostin C. Neither superfusion of the neuron with nordihydroguaiaretic acid (NDGA) nor superfusion with indomethacin caused any changes in Io(CT). These results suggest that extracellular CT can induce a slow outward current associated with a decrease in Na+ conductance, mediated by a receptor-controlled increase in intracellular cyclic adenosine 3',5'-monophosphate.

1-Methyl-3-isobutylxanthine↗

PubMed1993

Expression of cytokine receptors in cultured neuronal and glial cells.

We investigated mRNA expression of cytokine receptors in three different types of glial cells and two neuronal line cells by the RT-PCR method. Microglia expressed mRNA for receptors of IL-3, -4, -6, -7, GM-CSF, and M-CSF. Astrocytes were positive for receptors of IL-6, -7, GM-CSF, and M-CSF. Oligodendrocytes were positive for receptors of IL-3, -4, -7, GM-CSF, and M-CSF. Neuronal cells expressed receptors of IL-6 and GM-CSF with very low levels. This is the first demonstration of cytokine receptor mRNA expression in isolated glial and neuronal cells.

Animals↗

PubMed1993

Transforming growth factor-beta suppresses activation and proliferation of microglia in vitro.

Transforming growth factor-beta (TGF-beta) has been shown to be produced in the central nervous system (CNS). The functions of TGF-beta, however, remain to be elucidated. We investigated the effects of TGF-beta on the proliferation, activation, and cytokine production of isolated microglia in vitro. TGF-beta dose-dependently suppressed the acid phosphatase activity of and formation of superoxide anion by LPS activated microglia. It also suppressed the IFN-gamma-induced expression of class II MHC Ag- and the production of cytokines, IL-1, IL-6, and TNF-alpha, by these cells. TGF-beta also inhibited the proliferation of microglia that was induced by either GM-CSF or M-CSF. Because various immunoregulatory cytokines are produced in the CNS that serve as autocrine or paracrine mediators it is suggested that TGF-beta could be a negative regulator in the CNS cytokine network. It may play a role in the development of various disease processes in the CNS by inhibiting the function of microglia in inflammation or in immunoregulation.

Animals↗

PubMed1993

Involvement of phosphoinositide turnover in ouabain inotropism.

We examined whether ouabain activities phospholipases and reinforces contraction force of papillary muscles through resultant second messengers. 2-Nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC), the inhibitor of phospholipase C (PLC), abolished the ouabain inotropy in rabbit papillary muscles. Calphostin C, the specific inhibitor of protein kinase C (PKC), also depressed the ouabain inotropy. 12-O-Tetradecanoylphorbor-13-acetate (TPA), the specific activator of PKC, enhanced the beat-to-beat phasic contractility at low concentrations. Radioenzymatic assay revealed that ouabain treatment doubled diacylglycerol (DG) content in excised papillary muscles. We concluded that ouabain activates PLC, and the resultant second messenger, DG, augments the cardiac contraction force through activation of PKC.

Animals↗

PubMed1993

Induction of in vitro tumor cell invasion of cellular monolayers by lysophosphatidic acid or phospholipase D.

Serum is known to be required for invasion or phagokinesis of certain tumor cells, although the mechanism of its action is not well understood yet. In the in vitro invasion assay system we have developed, MM1 cells exhibiting extensive invasiveness against cultured mesothelial cell monolayers in the presence of 10% fetal calf serum did not invade them without serum. Human small cell lung cancer (OC10) cells also required serum in invasion. Serum could be completely substituted by oleoyl-lysophosphatidic acid (LPA) or bacterial phospholipase D (PLD). Phosphatidic acid also had an invasion-inducing activity, though to a lesser degree. Since human ovarian cancer (RMUG-S) cells require neither serum, LPA nor the PLD for invasion of mesothelial cell monolayers, the production of phospholipid like LPA, a candidate for intracellular second messenger, in tumor cells seems critical for the invasion by MM1 cells or OC10 cells. This result suggests a possible participation of particular signaling cascade, PLD-LPA(PA) system, in the invasion of certain tumor cells.

Animals↗

PubMed1993

Production of interleukin-5 by mouse astrocytes and microglia in culture.

Interleukin (IL)-5 was originally isolated as a B cell growth factor derived from T cells and is known as a multipotent cytokine. We found that IL-5 was detected in the cultures of microglia and astrocytes by both the enzyme-linked immunosolvent assay (ELISA) and bioassay with IL-5-dependent cell line, T88M. We also found that microglia and astrocytes expressed IL-5 mRNA. IL-5 receptor mRNA, however, was not detected in these cells. Stimulation with interferon-gamma increased expression of IL-5 in astrocytes and microglia. These results suggest that IL-5 produced by brain cells may be involved in the interaction between brain cells and immune cells in the brain.

Animals↗

PubMed1993

Regulation of astrocyte proliferation by prostaglandin E2 and the alpha subtype of protein kinase C.

We found that astrocytes expressed the alpha subtype of protein kinase C. Treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) caused cultured astrocytes to proliferate. This effect of TPA was blocked by staurosporine, a potent protein kinase C inhibitor, suggesting the involvement of protein kinase C in astrocyte proliferation. Indomethacin, an inhibitor of prostaglandin formation, enhanced both the normal and TPA-induced proliferation of astrocytes. Authentic prostaglandin E2 blocked this effect of indomethacin and also partially blocked the effect of TPA, suggesting that the intracellular mechanisms involved in prostaglandin E2-regulated astrocyte growth might differ from those acting in protein kinase-dependent growth. The effect of prostaglandin E2 was blocked by a specific anti-prostaglandin E2 polyclonal antibody. Cultured astrocytes and microglia produced and released prostaglandin E2 in response to stimulants such as lipopolysaccharide, TPA, and lymphokines. Since the sensitivity of astrocytes and microglia to these stimuli was different, prostaglandin E2 may differentially regulate astrocyte proliferation under different physiological conditions, acting in an autocrine fashion for astrocytes and in a paracrine fashion for microglia.

Alkaloids↗

PubMed1993

Specific expression of a complex sialyl Lewis X antigen on high endothelial venules of human lymph nodes: possible candidate for L-selectin ligand.

L-selectin is a cell adhesion molecule that mediates homing of lymphocytes to the peripheral lymph nodes and is speculated to bind to the carbohydrate determinant which is specifically expressed by the endothelial cells of high endothelial venules (HEVs) in the peripheral lymph nodes. One of the murine monoclonal antibodies (2H5, IgM, kappa), which was raised against sialyl LeX-active glycolipids which have long and complicated carbohydrate structures, was found to react strongly to the HEV endothelial cells of the human peripheral lymph nodes, while the typical anti-sialyl LeX antibodies SNH-3, FH-6 and CSLEX-1 failed to detect the antigen on HEV under the same condition. This new antibody was reactive to essentially all endothelial cells of HEV in the peripheral lymph nodes, and moderately to some endothelial cells in Payer's patches and appendices, but never reacted with the endothelial cells of post capillary venules in the spleen, thymus, or other organs. The 2H5 antibody detected three major glycoproteins of 90, 110 and 250 kDa, the most abundant molecular species being 110 kDa, in the stroma of human lymph nodes. In Stamper-Woodruff assays employing cryostat sections of human lymph nodes, the 2H5 antibody significantly inhibited the adhesion of peripheral lymphocytes to the endothelial cells of HEV. These results indicate that the carbohydrate antigens defined by the 2H5 antibody, most probably sialyl LeX determinants having complex carbohydrate structures, serve as the ligand for L-selectin on HEV endothelial cells.

Antibodies, Monoclonal↗

PubMed1993

Effect of a peptide leukotriene receptor antagonist, ONO-1078, on guinea-pig models of asthma.

Peptide leukotrienes have been suggested to play an important role in bronchial asthma. As antigen-induced bronchoconstrictions, airway hyperreactivity, and pulmonary eosinophil accumulation are characteristics of the pathology of asthma, we investigated the effect of a peptide leukotriene receptor antagonist, ONO-1078, on these responses using guinea-pig models of asthma. Oral administration of ONO-1078 (3 mg/kg) significantly inhibited slow-reacting substance of anaphylaxis-mediated bronchoconstriction induced by i.v. administered ovalbumin. ONO-1078 (30-100 mg/kg), when administered orally both 1 h before and 4 h after ovalbumin challenge, significantly reduced immediate- and late-phase asthmatic responses, with peak responses occurring immediately and 5-11 h after challenge with inhaled ovalbumin. Oral administration of ONO-1078 significantly reduced the airway hyperreactivity (10-30 mg/kg) and the pulmonary eosinophil accumulation (30-100 mg/kg) observed 4 and 24 h after ovalbumin challenge, respectively. These results suggest that ONO-1078 may be of therapeutic use for bronchial asthma.

Acetylcholine↗

PubMed1993

Nipradilol inhibits rat mesangial cell mitogenesis through the activation of soluble guanylate cyclase.

Nipradilol is a beta-adrenoreceptor blocking agent, whose structure contains an NO2 group. Thus, it is possible that it modulates the function of glomerular mesangial cells through the activation of soluble guanylate cyclase. To prove this hypothesis, we examined the effect of nipradilol on soluble guanylate cyclase, intracellular cyclic guanosine monophosphate (cGMP) accumulation, and the mitogenesis of cultured rat glomerular mesangial cells. Nipradilol increased intracellular cGMP accumulation in a dose-dependent manner through the activation of soluble guanylate cyclase. Furthermore, nipradilol inhibited the incorporation of [3H]thymidine into the mesangial cells stimulated by 2.5% fetal bovine serum in a dose-dependent manner. These results indicate that nipradilol may modulate mesangial cell function through an increase in intracellular cGMP resulting from the activation of soluble guanylate cyclase.

Adrenergic beta-Antagonists↗

PubMed1993

Stable expression of guinea pig NADPH-cytochrome P450 reductase and monkey P4501A1 cDNAs in Chinese hamster cells: establishment of cell lines highly sensitive to aflatoxin B [corrected].

To the cell line (A-15) expressing monkey P4501A1, which was developed from a Chinese hamster fibroblast cell line (CHL), a guinea pig [corrected] cDNA encoding NADPH-cytochrome P450 reductase was introduced and the transformants (designated AR-10, AR-13, and AR-18) stably expressing the reductase of increased level were established. The high-level expression of the reductase was confirmed by Northern and Western blot analyses and by measurement of the reductase activity in microsomes. The transfected clones showed 4- to 11-fold higher activity of the reductase than the parental cells. These cells showed about 9-fold higher sensitivity toward aflatoxin B1 (AFB1) cytotoxicity than A-15 cells and about 330-fold more than parental CHL cells. No difference in sensitivity was observed between CHL and the CHL-derived clones (CR-50, CR-52, and CR-68) expressing high levels of the reductase alone. Increased sensitivity of AR-10 cells was also observed with respect to sterigmatocystin cytotoxicity. Furthermore, in the assay for the induction of chromosomal aberrations, these clones were highly sensitive to AFB1. These results indicate that the level of the P450 reductase existing in parental CHL cells is not sufficient for maximal activity of monkey P4501A1.

Aflatoxin B1↗