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Biomedical subjects

M Ohno

Publications and source records attributed to M Ohno.

At least 361 records · Page 20Linked to original sources

Myotoxicity and physiological effects of three Trimeresurus flavoviridis phospholipases A2.

When basic proteins I and II from Trimeresurus flavoviridis (Habu snake) venom, which are Lys-49-phospholipase A2 (PLA2) with low activity, were injected intramuscularly into mice, myonecrosis was induced accompanied by a rapid increase of plasma creatine kinase level. This increase was about 2 times greater than that raised by highly active T. flavoviridis Asp-49-PLA2 which has been regarded as a myotoxic factor. Calcium-dependent depolarization of frog muscle fibers was observed with basic proteins I and II but not with Asp-49-PLA2. Indirect hemolysis of rat erythrocytes was induced by Asp-49-PLA2 but not by basic proteins I and II. Myotoxicity and depolarization effects appear to be not necessarily related to lipolytic activity of proteins although hemolytic effects is in parallel to lipolytic potency. Light microscopic observations of muscle preparations treated with three PLA2s showed similar histological changes, i.e., myolytic necrosis without hemorrhage and infiltration of polymorphonuclear cells. The structural and functional elements of PLA2s for eliciting myotoxicity are discussed.

Amino Acid Sequence↗

Effects of intrahippocampal injections of N-methyl-D-aspartate receptor antagonists and scopolamine on working and reference memory assessed in rats by a three-panel runway task.

In order to elucidate the roles of hippocampal N-methyl-D-aspartate-type excitatory amino acid receptors in working and reference memory in rats, the effects of intrahippocampal injections of selective and competitive N-methyl-D-aspartate receptor antagonists such as CGS 19755 (cis-4-phosphonomethyl-2-piperidine carboxylic acid), 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid and 2-amino-5-phosphonovaleric acid on this behavior were examined with a three-panel runway task. The results were compared with the effect of the muscarinic receptor antagonist scopolamine. In the working memory task, CGS 19755 and 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid at 10 and 32 ng/side, injected bilaterally into the dorsal hippocampus before testing, produced a significant increase in the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points). This also occurred after the rats were given systemic injection of these drugs at 3.2 and 10 mg/kg. In the reference memory task, neither CGS 19755 nor 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid affected the number of errors, whether given at doses up to 32 ng/side intrahippocampally or up to 10 mg/kg systemically. Working memory errors also increased significantly after intrahippocampal injections of d-2-amino-5-phosphonovaleric acid at 100 and 320 ng/side, but were not affected by I-2-amino-5-phosphonovaleric acid at doses up to 1 microgram/side. On the other hand, intrahippocampal scopolamine at 1.0 and 3.2 micrograms/side increased significantly working memory errors, without affecting reference memory errors.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗

[Overt leukemia from MDS associated with marked basophilia].

A 52-year-old woman was admitted to our hospital because of leukocytosis. She had been diagnosed with RAEB in another hospital in past time. At the admission, the white cell count was 30,900/microliter with blasts (14.0%) and marked basophilia (49.0%). Bone marrow aspiration revealed with 30.2% blasts and 21.1% basophils. Having obtained those results, diagnosis of RAEB in transformation was made. After admission, number of basophils in peripheral blood increased gradually, and level of histamine in serum was elevated significantly. Multiple peptic ulcers in stomach and bowel and high fever were induced due to histaminemia. Despite several therapy she died because of respiratory failure and septisemia. Although the mechanism of basophilia in this patient could not be clarified, there was a possibility that basophilia in this patient might be differentiated from leukemic clone because almost basophils in peripheral blood were mature and those had many granules including metachromasia by stained with toluidine blue.

Basophils↗

[Recurrent fusiform aneurysm of the internal carotid artery; a case report].

A 61-year-old woman was referred to our department on February 12, 1991, due to a fusiform aneurysm of her left internal carotid artery (ICA). She had received aneurysm surgery twice in other hospitals in the past. The first operation, in June, 1980, was for an unruptured, symptomatic left internal carotid-posterior communicating aneurysm and the aneurysm disappeared completely after the neck clipping procedure was carried out by one of the authors. In November, 1990, she suffered from subarachnoid hemorrhage with a hematoma in the left frontal lobe. A ruptured anterior communicating aneurysm was clipped in another hospital, where abnormal dilatation of the left ICA was pointed out. She was referred to our department after a ventricular peritoneal shunt operation. Though the postoperative angiogram performed in 1980 had shown complete disappearance of the left IC-PC aneurysm, it was presumed that the fusiform aneurysm which she presented at our department was recurrent because it existed in almost the same place as the aneurysm which had been clipped. It was also in contact with a clip applied in 1980. In accord with the patient's desire to receive surgery, the fusiform aneurysm was operated on directly, and it was remarkably reduced in size by dome clipping. During a clip, a Sugita booster clip was useful for preventing a slip-out of the clip applied on the aneurysmal dome. The patient was discharged about 20 days after the operation and returned to her usual life. A recurrent fusiform aneurysm of the ICA arising after the neck clipping of IC-PC aneurysm has rarely been encountered.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneurysm↗

[Clinical value of PMN elastase activity before reperfusion therapy in acute myocardial infarction: comparison with clinical characteristics, reperfusion events and myocardial damage].

Many recent studies demonstrate that neutrophils may be involved in the genesis and propagation of myocardial ischemia and reperfusion injury. Clinical value of PMN elastase activity before reperfusion which is released from activated polymorphonuclear leucocyte were evaluated in 30 patients with acute myocardial infarction. 19 patients with normal or moderately elevated PMN elastase activity (G1: less than 200 micrograms/l) revealed similar clinical characteristics before reperfusion therapy, compared to 11 patients with extremely high PMN elastase activity (Group 1: greater than or equal to 200 micrograms/l). But Group 1 represented fewer incidence of reperfusion events (Group 1 2/19, Group 2 7/11, p less than 0.01) such as arrhythmia, BP down, re-elevation of ST segments, and increased chest pain just after reperfusion, and higher incidence of salvaged myocardium in the risk area (Group 1 5/11, Group 2 4/19 p less than 0.1) evaluated by Tc-99m PYP, T1-201 dual SPECT, than Group 2. Wall motion analysis also showed that both global and regional wall motion were severely depressed in Group 2 compared with Group 1 (Group 1: Global EF 66.6 +/- 13.5, Extent 26.5 +/- 17.4, Severity 63.1 +/- 48.5, Group 2: Global EF 51.2 +/- 10.6, Extent 40.1 +/- 16.3, Severity 112.8 +/- 55.5, p less than 0.01 for Global EF, Extent, and p less than 0.05 for Severity). These data suggest that leucocyte activation before reperfusion may play important role in the genesis of reperfusion injury.

Aged↗

[Pharmacokinetics of carboplatin after intraperitoneal administration and clinical effect in ovarian cancer].

The patients with ovarian cancer are apt to combine peritonitis carcinomatosa (PC). The effect of intraperitoneal (IP) administration of CDDP against peritonitis carcinomatosa was examined. Hydration was not necessary when CBDCA was injected, because nephrotoxicity of CBDCA was very low compared to CDDP. We studied pharmacokinetics of IP-CBCCA and its efficacy and safety. Four hundreds and fifty mg of CBDCA was dissolved in 1,000 ml of saline and administrated through the subcutaneously implanted Infuse-A-Port for 60 minutes. Complete response was 25%. The platinum concentration in the ascites (injected saline) decreased to 90.8 micrograms/ml at 2 hr after administration and to 3.8 micrograms/ml at 24 hrs, and 79.7 97.5% existed as free Pt. The concentration of serous Pt reached to 6.2 micrograms/ml at 15 min. and was kept at 6-8 micrograms/ml. and 52.4-92.7% existed as free Pt in serum. Pt was excreted to urine and reached to the peak concentration at 4 hr. Adverse effect was mainly myelotoxicity without renal toxicity and emesis. Leukocytopenia of grade 4 was 14.3%, thrombocytopenia was 25.0%. We tried IP administration to the outpatients. The doses were mainly 300 mg, but in some cases, it was escalated to 450 mg, Adverse effect of 300 mg was thrombocytopenia of grade 4 (4.8%). These results suggest that IP administration of CBDCA seemed to be a new method as locosystemic chemotherapy. We demonstrated new chemotherapeutic method to outpatients.

Adenocarcinoma↗

Responses of human gastroepiploic arteries to vasoactive substances: comparison with responses of internal mammary arteries and saphenous veins.

We examined the responses of human gastroepiploic arteries to histamine, serotonin, and norepinephrine, comparing those of internal mammary arteries and saphenous veins. Fresh specimens of the vessels were obtained intraoperatively from 21 patients. The vessels were suspended in organ chambers to record isometric tensions. With gastroepiploic arteries, histamine induced relaxations in the endothelial rings (85% +/- 7%) but failed to induce any contractions or relaxations in the rings without endothelium. The relaxations were prevented by methylene blue or hemoglobin and the H1-histaminergic receptor antagonist chlorpheniramine. With internal mammary artery rings with endothelium, histamine at a low concentration (10(-8) to 10(-5.5) mol/L) induced relaxations (53% +/- 12%) but evoked contractions at a higher concentration (10(-5) to 10(-4.5) mol/L). With saphenous veins, histamine caused only contractions. Serotonin induced markedly greater contractions in saphenous veins than in either artery. The endothelium inhibited the maximal contraction in response to serotonin in both arteries but not in veins. With the gastroepiploic artery, the responses to norepinephrine and serotonin were similar to those of the internal mammary artery. Histamine induces endothelium-dependent relaxations only, and histaminergic receptors that induce contractions may be absent on vascular smooth muscle cells. These vasoactive properties may contribute to the high patency as a coronary graft.

Acetylcholine↗

Rapid colorimetric assay for the quantification of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6).

The methods in general use for quantifying leukemia inhibitory factor (LIF) activity involve measurements of suppression of proliferation or stimulation of phagocytic activity of mouse myelocytic leukemia (M1) cells. We have developed a novel assay for LIF activity which consists of measuring MTT reduction by M1 cells. The ability of M1 cells to reduce MTT correlates with the level of LIF used for stimulation. The MTT assay of LIF is much quicker than previously used quantitation methods and it is just as sensitive. The MTT assay can also be used to quantify IL-6.

Animals↗

Glycosylation at the Fab portion of myeloma immunoglobulin G and increased fucosylated biantennary sugar chains: structural analysis by high-performance liquid chromatography and antibody-lectin enzyme immunoassay using Lens culinaris agglutinin.

An antibody-lectin enzyme immunoassay technique which had been developed for the analysis of sugar chains of alpha-fetoprotein (N. Kinoshita et al., Clin. Chim. Acta, 179: 143-152, 1989) was used for analysis of sugar chains of myeloma immunoglobulin G (IgG). The IgG sugar chains of four of nine patients with myeloma were found to be highly reactive to Lens culinaris agglutinin as compared with those of six normal controls and 177 patients without myeloma. This reflected a high L. culinaris agglutinin/concanavalin A ratio. The IgGs of these patients were found to have highly sialylated, fucosylated, and bisected biantennary sugar chains at Fab portions as judged by the lectin-blotting technique as well as by high-performance liquid chromatography analysis. These results indicate that some of the myeloma IgG proteins undergo unusual glycosylation processes.

Carbohydrate Sequence↗

Effect of staurosporine, a protein kinase C inhibitor, on impairment of working memory in rats exposed to cerebral ischemia.

A 5-min period of cerebral ischemia induced in rats by the four-vessel occlusion method increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) assessed by a working memory procedure applied in a three-panel runway task. The protein kinase C (PKC) inhibitor, staurosporine 0.03 and 0.1 mg/kg, administered immediately after blood flow reperfusion, significantly reduced the increase in errors expected to occur 24 h after 5 min of ischemia. However, administration of staurosporine 0.1 mg/kg 6 h after ischemia had no effect on the increase in errors. The protective effect of staurosporine suggests that the enhanced PKC activity during the early reperfusion phase plays a crucial role in the post-ischemic impairment of working memory.

Alkaloids↗

Interaction with phospholipid bilayers, ion channel formation, and antimicrobial activity of basic amphipathic alpha-helical model peptides of various chain lengths.

Basic amphipathic alpha-helical peptides Ac-(Leu-Ala-Arg-Leu)3 or 4-NHCH3 (4(3) or 4(4)) and H-(Leu-Ala-Arg-Leu)3-(Leu-Arg-Ala-Leu)2 or 3-OH (4(5) or 4(6)) were synthesized and studied in terms of their interactions with phospholipid membranes, biological activity, and ion channel-forming ability. CD study of the peptides showed that they form alpha-helical structures in the presence of phospholipid liposomes and thus they have amphipathic distribution of the side chains along the axis of the helix. A leakage study of carboxyfluorescein encapsulated in phospholipid vesicles indicated that the peptides possess a highly potent ability to perturb the membrane structure. Membrane current measurements using the planar lipid bilayer technique revealed that the peptide 4(6), which was long enough to span the lipid bilayer in the alpha-helical structure, formed cation-selective ion channels at a concentration of 0.5 microM in a planar diphytanoylphosphatidylcholine bilayer. In contrast, other shorter peptides failed to form discrete and stable channels though they occasionally induced an increase in the membrane current with erratic conductance levels. The probability of detecting a conductance increase was in the order of 4(6) greater than 4(5) greater than 4(4) greater than 4(3), which corresponds to the order of the peptide chain lengths. Furthermore, 4(6) but not 4(5) showed an antimicrobial activity against both Gram-positive and -negative bacteria. The structure of ion channels formed by 4(6) and the relationship between the peptide chain length and biological activity of the synthetic peptides are discussed.

Amino Acid Sequence↗

[MR imaging of pontine infarction within 2 weeks after ictus].

Magnetic resonance (MR) images of 10 patients with pontine infarction were reviewed. A total of 17 examinations were performed on a 1.5 Tesla high-field scanner (GE) within two weeks after ictus. The infarcted area was detected by MR as early as 20 hours after stroke in one case. However, MR images obtained in two cases three and nine hours after onset were unremarkable. It is therefore suggested that follow-up study should be performed when initial MR images within 20 hours postictus are normal. T1-weighted images at four, nine and twelve days after ictus were interpreted as normal. In two of these three examinations, the infarcted areas were clearly demonstrated as hyperintense lesions on T2-weighted images. In the other examination, however, an area of mildly increased signal intensity was seen on T2-weighted images. This case suggests that the fogging effect is also observed on MR imaging and that a small pontine infarction may be overlooked during the subacute stage. Basilar artery occlusion was detected as an absence-of-flow void in three of the ten patients. In conclusion, MR imaging proved to be a relatively useful diagnostic modality for evaluating acute and subacute pontine infarctions.

Acute Disease↗

Blockade of 5-HT2 receptors protects against impairment of working memory following transient forebrain ischemia in the rat.

The effects of the 5-HT2 receptor antagonists pirenperone, cinanserin and ritanserin on impairment of working memory in an animal model of cerebral ischemia were investigated, using a three-panel runway task. A 5-min period of ischemia caused a significant increase in the number of errors (attempts to pass through two incorrect panels of the 3 panel gates at 4 choice points). Pirenperone at 0.32 and 1.0 mg/kg, cinanserin 10 mg/kg and ritanserin 3.2 mg/kg administered i.p. immediately after blood flow reperfusion significantly reduced the increase in errors expected to occur 24 h after the 5 min of ischemia. These results suggest that the blockade of 5-HT2 receptors prevents the impairment of working memory following transient forebrain ischemia.

Animals↗

[MR imaging of medullary infarction].

Magnetic resonance (MR) images of 20 patients with medullary infarction have been reviewed. All patients were imaged on a 1.5 Tesla high-field scanner (GE, Signa). Clinical diagnoses of these 20 patients were Wallenberg's syndrome (15), cerebellar infarct (3), right hemiparesis (1), and multiple cerebral infarcts (1). Locations of infarct were right lateral (8), right postero-lateral (2), left lateral (5), left postero-lateral (4) and left anterior (1). Associated ipsilateral cerebellar infarcts were observed in six patients. Ipsilateral vertebral artery (VA) occlusions were detected in six patients, and VA aneurysm in two. Thus, MR imaging is a pertinent diagnostic modality for evaluating medullary infarction and associated vascular diseases.

Adult↗

Conformational studies of amphipathic alpha-helical peptides containing an amino acid with a long alkyl chain and their anchoring to lipid bilayer liposomes.

In order to investigate the conformation and orientation of lipid-bound peptides and proteins in the lipid bilayer, basic amphipathic alpha-helical peptides with a long alkyl chain, palmitoyl-(Leu-Ala-Arg-Leu)3-NHCH3 (P-4(3)) and Ac-Leu-Ala-Arg-Leu-Trp-Amy-Arg-Leu-Leu-Ala-Arg-Leu-NHCH3 (Amy-4(3), Amy; alpha-aminomyristic acid) were designed and synthesized. The conformational features and spectroscopic behavior in a buffer solution and in neutral and acidic liposomes were studied by CD, dye-leakage, and fluorescence measurements. The CD data indicated that P-4(3) took an alpha-helical structure in aqueous solution and in neutral and acidic liposomes. On the other hand, Amy-4(3) took a beta-structure in aqueous solution and an alpha-helical structure in neutral and acidic liposomes. The conformational change of Amy-4(3) was confirmed by fluorescence study on lipid titration of the peptide. The dye-leakage experiment showed that both peptides interacted with acidic liposomes to perturb them, but less effectively than Ac-(Leu-Ala-Arg-Leu)3-NHCH3 (4(3)) which has no long alkyl group. Based on these results, a discussion is made concerning the conformation and orientation of peptides in aqueous solution and in the lipid bilayer.

Amino Acid Sequence↗

Effect of the kappa-receptor agonist, U-50,488H, on cerebral ischemia-induced impairment of working memory assessed in rats by a three-panel runway task.

The effect of U-50,488H, a selective kappa-receptor agonist, on memory functions in an animal model of cerebral ischemia was investigated by use of a three-panel runway task. A 5-min period of ischemia caused a significant increase in the number of errors (pushes made on the two incorrect panels of the three panel-gates at four choice points) in a working memory task but it did not impair a reference memory task. U-50,488H at 10 and 32 mg/kg, administered i.p. immediately after blood flow restoration significantly reduced the increase in errors expected to occur in a working memory task assessed 24 h after 5 min of ischemia. This protective effect of U-50,488H on amnesia in the ischemic rat was antagonized by the kappa-receptor antagonist, MR-2266. We conclude that U-50,488H prevents the impairment of working memory following transient forebrain ischemia, an event mediated by the activation of the kappa-opioid receptor.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗