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Biomedical subjects

M Ohno

Publications and source records attributed to M Ohno.

At least 307 records · Page 17Linked to original sources
PubMed1993

Proliferation of microglia/macrophages in the demyelinating CNS and PNS of twitcher mouse.

In demyelinating lesions in the central and peripheral nervous systems of twitcher mouse, a murine model of globoid cell leukodystrophy, marked increases of [3H]thymidine-labeled elements including Mac-1 immunopositive (Mac-1+) microglia/macrophages was observed. Their proliferative activities were already pronounced at the postnatal day (P) 20, an early stage of demyelination, peaked at P30 and then declined at P45, at the terminal stage of the disease. Many of the [3H]thymidine-labeled Mac-1+ cells had morphological features of ramified microglia. Macrophage-like Mac-1+ cells were less frequently labeled. The results of this study showed that (1) microglia/macrophages proliferated in the genetic demyelinating lesions, (2) many dividing Mac-1+ cells had the shape of ramified microglia and (3) the rate of proliferation declined in later stages when reactive microglia/macrophages were abundant in the lesions. The temporal events of this study suggest that signal(s) from the degenerating myelin or myelin-forming cells stimulate(s) cellular proliferation and that ramified microglia were one of the principal-dividing elements in the lesion. The biological mechanisms underlying the decline of the proliferative activity of microglia require further studies.

Animals↗
PubMed1993

Regulation of RNA processing and transport by a nuclear guanine nucleotide release protein and members of the Ras superfamily.

The RCC1 gene of mammals encodes a guanine nucleotide release protein (GNRP). RCC1 and a homolog in Saccharomyces cerevisiae (MTR1/PRP20/SRM1) have previously been implicated in control of mRNA metabolism and export from the nucleus. We here demonstrate that a temperature-sensitive fission yeast mutant which has a mutation in a homologous gene, and two of three additional (mtr1/prp20/srm1) mutants accumulate nuclear poly(A)+ RNA at 37 degrees C. In S.cerevisiae, maturation of rRNA and tRNA is also inhibited at 37 degrees C. Nevertheless, studies with the corresponding BHK-21 cell mutant indicate that protein import into the nucleus continues. MTR1 homologs regulate RNA processing at a point which is distinct from their regulation of chromosome condensation since: (i) poly(A)+ RNA accumulation in the fission yeast mutant precedes chromosome condensation, and (ii) unlike chromosome condensation, accumulation of nuclear poly(A)+ RNA does not require p34cdc28 kinase activation or protein synthesis. Moreover, experiments involving inhibition of DNA synthesis indicate that the S.cerevisiae homolog does not govern cell cycle checkpoint control. Since RCC1p acts as GNRP for Ran, a small nuclear GTPase of the ras superfamily, we have identified two homologs of Ran in S.cerevisiae (CNR1 and CNR2). Only CNR1 is essential, but both code for proteins extremely similar to Ran and can suppress mtr1 mutations in allele-specific fashion. Thus, MTR1 and its homologs appear to act as GNRPs for a family of conserved GTPases in controlling RNA metabolism and transport. Their role in governing checkpoint control appears to be restricted to higher eukaryotes.

Amino Acid Sequence↗
PubMed1993

Chymotrypsin inhibitory conformation of dipeptides constructed by side chain-side chain hydrophobic interactions.

A complete series of configurational isomers (L-L, L-D, D-L and D-D) of a dipeptide Leu-Phe benzyl ester have been synthesized and assayed for chymotrypsin. In the conformational analysis by 400 MHz 1H NMR, the L-D and D-L isomers, but not the L-L and D-D isomers, showed fairly large upfield shifts (0.2-0.4 ppm) of Leu-beta CH2 and gamma CH proton signals, indicating the presence of shielding effects from the benzene ring. In addition to distinct signal splitting of Phe-beta CH2, the NOE enhancement observed between Leu-delta CH3 and Phe-phenyl groups revealed that these groups are in close proximity. These data indicated that L-D and D-L isomers form a hydrophobic core between side chains of adjacent Leu and Phe residues. When the dipeptides were examined for inhibition of chymotrypsin using Ac-Tyr-OEt as a substrate, the L-L isomer showed no inhibition, itself becoming a substrate. However, the other three isomers inhibited chymotrypsin in a competitive manner, and the D-L isomer was strongest with Ki of 2.2 x 10(-5) M. It was found that the D-L isomer was only slowly hydrolysed but the L(or D)-D isomer was not. H-D-Phe-L-Leu-OBzl with the inverse sequence of H-D-Leu-L-Phe-OBzl inhibited chymotrypsin more strongly (Ki = 6.3 x 10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Chymotrypsin↗
PubMed1993

Coenzyme Q10 and coronary artery disease.

It has been postulated that oxidatively modified low-density lipoprotein (LDL) contributes to the genesis of atherosclerosis. Ubiquinone has been suggested to be an important physiological lipid-soluble antioxidant and is found in LDL fractions in the blood. We measured plasma level of ubiquinone using high-performance liquid chromatography and plasma levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides in 245 normal subjects (186 males, 59 females) and in 104 patients (55 males, 49 females) who had coronary artery disease not receiving pravastatin and 29 patients (12 males, 17 females) receiving pravastatin. In the normal subjects, the plasma ubiquinone levels did not vary with age. In the patient groups, the plasma total cholesterol and LDL levels were higher and the plasma ubiquinone level lower than in the normal subject group. The LDL/ubiquinone ratio was higher in the patient groups. We found that ubiquinone level, either alone or when expressed in relation to LDL levels, was significantly lower in the patient groups compared with the normal subject group. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor is thought to prevent atherosclerosis, however, it also inhibits ubiquinone production. The present study revealed that HMG CoA reductase inhibitor decreased plasma cholesterol level, and that it did not improve either the ubiquinone level or the LDL/ubiquinone ratio. From these results, the LDL/ubiquinone ratio is likely to be a risk factor for atherogenesis, and administration of ubiquinone to patients at risk might be needed.

Coronary Disease↗
PubMed1993

Olivary degeneration after cerebellar or brain stem haemorrhage: MRI.

Magnetic resonance (MR) images of seven patients with olivary degeneration caused by cerebellar or brain stem haemorrhages were reviewed. In four patients with cerebellar haemorrhage, old haematomas were identified as being located in the dentate nucleus; the contralateral inferior olivary nuclei were hyperintense on proton-density- and T2-weighted images. In two patients with pontine haemorrhages, the old haematomas were in the tegmentum and the ipsilateral inferior olivary nuclei, which were hyperintense. In one case of midbrain haemorrhage, the inferior olivary nuclei were hyperintense bilaterally. The briefest interval from the ictus to MRI was 2 months. Hypertrophic olivary nuclei were observed only at least 4 months after the ictus. Olivary degeneration after cerebellar or brain stem haemorrhage should not be confused with ischaemic, neoplastic, or other primary pathological conditions of the medulla.

Aged↗
PubMed1993

Usefulness of sodium chloride as a nondiffusible indicator in the measurement of extravascular lung thermal volume in dogs.

The authors examined the usefulness of sodium chloride as a nondiffusible indicator during the first passage through dogs' lungs, before and after increased-permeability pulmonary oedema produced by an intravenous injection of alloxan. With an injection of a mixture of ice-cold 3 per cent sodium chloride and indocyanine green dye (a nondiffusible reference indicator), the authors simultaneously recorded three dilution curves from the aortic root: dye dilution, thermal and blood electrical conductivity dilution curves in six dogs. The mean transit time of sodium chloride in the conductivity dilution curve was significantly different from, but fairly equal to, that of indocyanine green dye (6.2 +/- 1.4 s (mean +/- SD) against 6.5 +/- 1.4 s (p < 0.01) in the baseline period, and 7.6 +/- 1.9 s against 8.4 +/- 2.1 s (p < 0.01) in the oedema period, respectively). The calculated extravascular lung thermal volume with the thermal and conductivity dilution method (Y, ml kg-1) correlated well with the gravimetrically determined extravascular lung mass in a total of 12 dogs, including six other dogs without intervention (x, g kg-1) (y = 0.72 x +3.03, r = 0.96). The authors conclude that sodium chloride is useful as a nondiffusible indicator in the first passage through the lungs, and that the thermal and conductivity dilution method is also useful for measuring extravascular lung water mass.

Animals↗
PubMed1993

Neuromuscular effects of pipecuronium during sevoflurane anesthesia compared with isoflurane and enflurane anesthesia.

We evaluated the neuromuscular effects of pipecuronium during anesthesia with equipotent concentrations of either sevoflurane, isoflurane or enflurane. Twenty-seven patients scheduled for minor elective otolaryngeal or plastic surgery were studied and randomly assigned to 3 groups, one group per anesthetic agent. Anesthesia was induced with thiamylal 5 mg.kg(-1) and the trachea was intubated with succinylcholine 1 mg.kg(-1), then anesthesia was maintained with 60% nitrous oxide in oxygen and sevolfurane, isoflurane or enflurane, depending on the group. Neuromuscular blocking effects were monitored by recording the electromyographic activity of the adductor pollicis muscle from supramaximal stimulation of the ulnar nerve at 10-s intervals. Pipecuronium 40 microg.kg(-1) was administered when electromyographic activity had reached a stable state, 30 min after succinylcholine administration. The maximum effect (% block of control) and clinical duration (time to 25% recovery) of pipecuronium were 99.1 +/- 1.4% and 63.7 +/- 14.7 min (mean +/- S.D.) for sevoflurane, 99.0 +/- 2.0% and 60.9 +/- 20.5 min for isoflurane, and 98.0 +/- 2.5% and 62.8 +/- 28.7 min for enflurane, respectively. There were no significant differences in these values between the anesthetics. Cardiovascular stimulant effects were not observed in any of the groups. We conclude that the effect of pipecuronium under seveflurane anesthesia is similar to that under isoflurane and enflurane anesthesia.

Clinical Trial↗
PubMed1993

Ameliorative effects of the centrally active cholinesterase inhibitor, NIK-247, on impairment of working memory in rats.

Using a three-panel runway task, the effects of NIK-247 on impairment of working memory produced by scopolamine, hippocampal lesions, and cerebral ischemia were investigated in rats; these effects were compared with those of the well-known cholinesterase inhibitors, tetrahydroaminoacridine (THA) and physostigmine. Intraperitoneal injection of scopolamine (0.56 mg/kg) significantly increased the number of errors (pushes made on the two incorrect panels of the three-panel gates located at four choice points). NIK-247 (3.2-18 mg/kg PO), THA (1-10 mg/kg PO), and physostigmine (0.1 and 0.32 mg/kg IP) dose-dependently reduced the increase in errors induced by scopolamine. NIK-247 (32 mg/kg) was also effective in reducing the increase in errors produced by lesions of the dorsal hippocampus. A 5-min period of cerebral ischemia markedly increased the number of errors. NIK-247 (3.2 and 10 mg/kg), given immediately after blood flow recirculation and again 20 min before the runway test carried out 24 h after ischemia, significantly reduced the increase in errors expected to occur after ischemia. Tetrahydroaminoacridine (3.2 mg/kg) and physostigmine (0.1 mg/kg) similarly reversed the increased errors in ischemic rats. These results suggest that NIK-247 alleviates the impairment of working memory produced by scopolamine, hippocampal lesions, and cerebral ischemia, possibly through activation of the central cholinergic system.

Acetylcholinesterase↗
PubMed1993

Amygdaloid NMDA and muscarinic receptors involved in working memory performance of rats.

In a three-panel runway task, the competitive N-methyl-D-aspartate (NMDA) receptor antagonist, 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid (CPP) (56 ng/side), injected bilaterally into the basolateral subdivision of the amygdala, significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel gates at four choice points) in a test of working memory. Intra-amygdaloid injection of the muscarinic receptor antagonist scopolamine (5.6 micrograms/side) also significantly increased working memory errors. In a test of reference memory, neither CPP nor scopolamine affected the number of errors when injected into the basolateral amygdala at doses up to 56 ng/side or 5.6 micrograms/side, respectively. These results indicate that processes mediated by NMDA and muscarinic receptors in the basolateral amygdala are involved in the performance of working memory, but not in reference memory.

Amygdala↗
PubMed1993

Purification, sequencing and characterization of single amino acid-substituted phospholipase A2 isozymes from Trimeresurus gramineus (green habu snake) venom.

Two phospholipases A2 named PLA2-III and IV were newly isolated from Trimeresurus gramineus (green habu snake) venom in addition to PLA2-I and II reported previously [ODA et al. (1991) Toxicon 29, 157; Fukagawa et al. (1992) Toxicon 30, 133]. Their isoelectric points were determined to be about 4.5. PLA2-III and IV exhibited almost unchanged lipolytic activity toward egg-yolk when compared with PLA2-I. The amino acid sequences were determined by sequencing the native proteins and the peptides produced by enzymatic (Achromobacter protease I and clostripain) and chemical (hydroxylamine) cleavages of the S-carboxamidomethylated derivative of the proteins. Both proteins consisted of 122 amino acid residues. When compared with PLA2-I, PLA2-III showed only a single amino acid substitution at the N-terminal position; namely from His to Asn. PLA2-IV also showed a single substitution from Ala to Asp at position 72. It was inferred that these amino acid substitutions between PLA2-I and PLA2-III or IV are due to the single base substitution at the corresponding codons of genes, which might be preserved independently. The unique presence of Phe at position 28, where Tyr is commonly located and assumed to be a part of the Ca(2+)-binding loop, was conserved in both PLA2-III and IV as in PLA2-I. There was no significant difference in the dissociation constants (4.3-5.2 x 10(-4) M) for Ca2+ between these PLA2S and Tyr-28-containing PLA2S. These results suggested that the p-hydroxy group of Try-28 does not play a crucial role in binding of PLA2S to Ca2+.

Amino Acid Sequence↗
PubMed1993

Discriminative stimulus properties of NIK-247 and tetrahydroaminoacridine, centrally active cholinesterase inhibitors, in rats.

The discriminative stimulus effect of the novel centrally active cholinesterase inhibitor, NIK-247, was investigated in rats and compared with that of tetrahydroaminoacridine (THA). Rats were trained to discriminate either 10 mg/kg NIK-247 or 1.8 mg/kg THA from saline in a two-lever food-reinforced procedure. The stimulus effect of NIK-247 was substituted for by the cholinesterase inhibitors, THA and physostigmine. The THA stimulus was substituted for by NIK-247 and physostigmine. The muscarinic receptor agonist arecoline substituted for the NIK-247 and THA stimuli. Both stimulus effects of NIK-247 and THA were blocked by the muscarinic antagonist scopolamine. The dopaminergic-activating drugs amantadine and lisuride substituted for the stimulus effects of NIK-247 and THA. However, neither the NIK-247 nor the THA stimulus was antagonized by the dopamine antagonists haloperidol, SCH 23390, and sulpiride. These results suggest that the discriminative stimulus effects of NIK-247 and THA are mediated by muscarinic receptors, and that the dopaminergic activity resulting from cholinergic activation may account for some part of both stimuli.

Aminoquinolines↗
PubMed1993

Blockade of hippocampal nicotinic receptors impairs working memory but not reference memory in rats.

In a three-panel runway task, intrahippocampal injection of the nicotinic receptor antagonist, mecamylamine (10 and 18 micrograms/side), significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) in a test of working memory. This increase in errors also occurred after rats were given IP mecamylamine (10 mg/kg). Mecamylamine did not affect the number of errors in a test of reference memory whether it was given at doses up to 18 micrograms/side intrahippocampally or up to 10 mg/kg IP. These results suggest that mechanisms mediated by hippocampal nicotinic receptors play a role in working memory but not in reference memory.

Animals↗
PubMed1993

Interaction between pullulanase from Klebsiella pneumoniae and cyclodextrins.

The interaction between pullulanase from Klebsiella pneumoniae and alpha-, beta-, and gamma-cyclodextrins and 6-O-alpha-glucosyl-alpha-cyclodextrin and 6-O-alpha-glucosyl-beta-cyclodextrin was examined by means of inhibition studies of the enzyme activity, UV difference spectroscopy, and flow calorimetry. All the above cyclodextrins were found to be competitive inhibitors, but beta-cyclodextrin and 6-O-alpha-glucosyl-beta-cyclodextrin showed strong inhibition, the inhibitor constants being two orders of magnitude less than those of alpha- and gamma-cyclodextrins. The difference spectra of beta-cyclodextrin were slightly but significantly different from those of the other cyclodextrins, showing blue shift of a few nanometers. Moreover, only beta-cyclodextrin has a positive entropy change upon binding with the enzyme; all the other cyclodextrins have negative values. These results show that the binding mode of beta-cyclodextrin is subtly different from those of alpha- and gamma-cyclodextrins.

Calorimetry↗
PubMed1993

Purification and characterization of UDP-N-acetylglucosamine: alpha-6-D-mannoside beta 1-6N-acetylglucosaminyltransferase (N-acetylglucosaminyltransferase V) from a human lung cancer cell line.

A beta 1-6N-acetylglucosaminyltransferase (GnT-V) [EC 2.4.1.155] which catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to alpha-D-6-mannoside has been purified up to 20,000-fold from the cultured supernatant of the QG small lung cancer cell line with a 37% yield. The isolation procedure included chromatography on phenyl-Sepharose, hydroxylapatite, UDP-hexanolamine Sepharose, and a biantennary sugar substrate (GnGn-bi-Asn) coupled to activated CH-Sepharose 4B. Sodium dodecyl sulfate gel electrophoresis under non-reducing conditions showed a single band of 73 kDa. Under reducing conditions, however, an additional component of 60 kDa was seen. Peptide mapping analysis indicated that both of these proteins were essentially identical, indicating that the 60-kDa component is probably a proteolytically cleaved form of the 73-kDa protein. Studies on the activity of the enzyme toward a variety of pyridylaminated sugars showed that the enzyme is most active toward triantennary (GnGnGn-tri-PA) and biantennary (GnGn-bi-PA) sugars. The Km values for GnGn-bi-PA and UDP-GlcNAc were 133 microM and 3.5 mM, respectively. These studies represent the first report of the enzymatic properties of a highly purified human GnT-V.

Acetylglucosamine↗
PubMed1993

Myocardial SPECT and left ventricular performance study using a single Tc-99m teboroxime injection. Comparison with thallium-201 myocardial SPECT.

Myocardial SPECT using teboroxime was compared to thallium SPECT in 26 patients undergoing cardiac catheterization. Agreement between thallium SPECT and teboroxime SPECT for the identification of myocardial segments was 209/235 (89%). A significant correlation was found in 15 patients between the left ventricular ejection fraction by teboroxime first-pass study and the ejection fraction by contrast ventriculography. In nine patients with myocardial infarction and/or multivessel coronary artery disease, the ejection fraction revealed a mean decrease from 0.52 at rest to 0.46 at exercise. Teboroxime makes it possible to perform an exercise first-pass study of left ventricular ejection fraction followed by myocardial perfusion imaging.

Adult↗
PubMed1993

Carboxyl-terminal heparin-binding fragments of platelet factor 4 retain the blocking effect on the receptor binding of basic fibroblast growth factor.

Platelet factor 4 (PF-4) blocks the binding of basic fibroblast growth factor (bFGF) to its receptor. In the present study, we constructed carboxyl-terminal fragments, which represent the heparin-binding region of the PF-4 molecule, and examined whether these synthetic peptides retain the blocking effects on the receptor binding of bFGF. Synthetic peptides inhibited the receptor binding of bFGF. Furthermore, they inhibited the migration and tube formation of bovine capillary endothelial cells in culture (these phenomena are dependent on endogenous bFGF).

Amino Acid Sequence↗
PubMed1993

Effects of acetylsalicylic acid on pulmonary vascular tone and membrane permeability in blood-perfused dog lung.

We studied the effects of acetylsalicylic acid (ASA) on pressor response, microvascular filtration coefficient (Kf), extravascular lung water, and plasma concentrations of cyclooxygenase- and 5-lipoxygenase-derived products in 21 blood-perfused dog lungs with constant flow. The lungs were perfused for 1 h with an intrapulmonary injection of saline as vehicle (n = 5), a low dose of ASA [136 +/- 25 (SD) micrograms/ml perfusate; n = 5], a high dose of ASA (1,006 +/- 278 micrograms/ml perfusate; n = 6), or alloxan (1,000 mg; n = 5). Alloxan significantly increased Kf and extravascular lung water, whereas neither the low nor high dose of ASA increased Kf or extravascular lung water. The ASA-induced increase in vascular resistance did not correlate with the extent of the decrease in perfusate 6-keto-prostaglandin F1 alpha or the ratio of perfusate 6-ketoprostaglandin F1 alpha to thromboxane B2. Moreover, ASA did not enhance the generation of perfusate leukotrienes B4, D4, or E4. We conclude that pulmonary microvascular permeability is unaltered by ASA and that neither the decrease in plasma prostacyclin nor the increase in plasma sulfidopeptide leukotrienes may account for ASA-induced pulmonary vasoconstriction.

6-Ketoprostaglandin F1 alpha↗