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Biomedical subjects

M Yasuda

Publications and source records attributed to M Yasuda.

At least 379 records · Page 21Linked to original sources

Detection of the unilateral vestibular recruitment phenomenon using the rotation test.

The possibility of detecting unilateral vestibular recruitment using the rotation test was examined. According to the analogy model of cochlear recruitment, the directional difference of rotation nystagmus reaches its maximum at the threshold stimulus intensity of the affected ear when recruitment is present, and the predicted maximum directional difference remains within the normal variation range when the contribution from the spontaneous nystagmus is removed. Moreover, there was no difference in the positive ratio of recruitment in the rotation test between the two groups evaluated as having positive and negative recruitment on the caloric test. From these results, detection of the unilateral vestibular recruitment phenomenon, when similar to the cochlear recruitment, was concluded to be difficult using the rotation test.

Hot Temperature↗

Interleukin-1 alpha enhances hepatotoxicity of tumor necrosis factor-alpha in galactosamine-sensitized mice.

The possible involvement of interleukin-1 alpha (IL-1 alpha) in the pathogenesis of murine hepatitis model induced with galactosamine and lipopolysaccharide (LPS) was investigated. The injection of 10 ng/mouse of LPS in combination with 10 mg/mouse of galactosamine into mice induced hepatic damage at 24 hours. Treatment with anti-mouse IL-1 alpha antiserum 30 min before galactosamine/LPS injection showed a tendency to reduce the liver injury, while pretreatment with anti-mouse tumor necrosis factor-alpha (TNF) antiserum significantly protected mice from liver injury. The use of recombinant murine TNF, instead of LPS, in combination with galactosamine could elicit hepatic damage, whereas recombinant murine IL-1 alpha could not substitute for LPS. However, recombinant murine IL-1 alpha enhanced the hepatotoxic effect of recombinant murine TNF in galactosamine-sensitized mice. These results suggest that TNF plays a major role in the pathogenesis of galactosamine/LPS hepatitis in mice and that IL-1 alpha acts synergistically with TNF in this hepatitis model.

Animals↗

Effect of zinc-carnosine chelate compound (Z-103), a novel antioxidant, on acute gastric mucosal injury induced by ischemia-reperfusion in rats.

The protective effect of a novel synthetic zinc-carnosine chelate compound, zinc N-(3-aminopropionyl)-L-histidine (Z-103), on the gastric mucosal injury induced by ischemia-reperfusion was studied in rats. Ischemia and reperfusion injury was produced on the rat stomach by applying a small clamp to the celiac artery for 30 min and by removal of the clamp for 30 min. The decrease in the gastric mucosal blood flow was not influenced by the treatment with Z-103. The increase in total area of the erosions on the stomach after ischemia-reperfusion and the increase in lipid peroxides in the gastric mucosa were significantly inhibited by the oral administration of Z-103. In addition, Z-103 inhibited lipid peroxidation of rat brain homogenate and liver microsome in vitro. These results suggest that the protective effect of Z-103 against the aggravation of gastric mucosal injury induced by ischemia-reperfusion may be due to its inhibitory effect on lipid peroxidation.

Animals↗

Relation between functions and conformational characteristics of modified nucleosides found in tRNAs.

Conformational characteristics of N4-acetyl-2'-O-methylcytidine (ac4Cm), 5-methyl-2'-O-methylcytidine (m5Cm) and N2-dimethyl-2'-O-methylguanosine (m2(2)Gm) found in tRNAs from extremely thermophilic archaebacteria were analyzed by proton NMR spectroscopy. The 2'-O-methylation of ac4C, m5C and m2(2)G was found to stabilize the C3'-endo form and therefore cause "conformational rigidity". In particular, the ac4Cm was found to be extremely rigid due to additive effects of the N4-acetylation and 2'-O-methylation. Therefore, tRNAs from the extremely thermophilic archaebacteria use the base modifications in combination with the 2'-O-methylation, resulting in stabilization of the A-type conformation at specific positions in the tRNAs even at very high temperatures. In contrast, mesophile tRNAs use for a given site only one of these ribose and base modifications each of which is effective enough by itself at ordinary temperatures. These findings are consistent with our previous findings that roles of a variety of post-transcriptional modifications are to regulate the conformational rigidity/flexibility which is essential for the tRNA functions.

Archaea↗

RGD-containing peptides inhibit experimental peritoneal seeding of human ovarian cancer cells.

A synthetic peptide containing the RGD (Arg-Gly-Asp) sequence is known to inhibit the attachment between cells and the extracellular matrix (ECM) in vitro, and also inhibit experimental pulmonary metastasis of murine melanoma cells in vivo. Prevention of peritoneal seeding by RGD-containing peptides has never previously been discussed. In this study, the inhibition of peritoneal seeding by RGD-containing peptides is examined, using the in vivo experimental peritoneal seeding model with human ovarian cancer cells (JHOC-1). Intraperitoneal (i.p.) inoculation of nude mice with JHOC-1 cells soon resulted in peritoneal seeding in all of the mice. Most of them expired within 4 to 80 weeks, and none survived for as long as 10 weeks. GRGDS (Gly-Arg-Gly-Asp-Ser) sequenced synthetic peptides were administered by i.p. injection after tumor cell inoculation following some regimens, and the changes in body weight and the periods of survival of the peptides-treated and untreated mice were observed. Intraperitoneal administration of 2mg/mouse of GRGDS peptides (every 8 hours, for 4 days, beginning just after tumor cell inoculation) significantly prolonged the survival periods of the tumor implanted mice. In this study, RGD-containing peptides were found to be able to prevent in vivo experimental peritoneal seeding by continual i.p. administration. This might indicate that RGD and integrins plays a critical role in peritoneal seeding as well as in hematogeneous metastasis.

Animals↗

[Acute megakaryoblastic leukemia with leukemia cutis, meningeal leukemia, and myelofibrosis].

A 64-year-old man was admitted to our hospital with leukopenia. On admission, leukocyte count in the peripheral blood was 1,600/microliters, containing 24.5% blasts of lymphoid appearance, which were negative for myeloperoxidase. A bone marrow aspiration showed hypoplasia with increased blasts (31.6%). The blasts were ultrastructurally positive for platelet peroxidase (PPO) and positive for platelet membrane glycoprotein IIb/IIIa complex. A diagnosis of acute megakaryoblastic leukemia was made. Chemotherapy with behenoyl-ara C (BH-AC) (150 mg/day) was transiently effective. However, after three months, numerous nodules without itching appeared over the entire body, particularly on the anterior chest. A biopsy of the skin lesion revealed a diffuse fibrosis with infiltrations of the blasts. Bone marrow aspirations were dry tap, and a bone marrow biopsy showed marked myelofibrosis. Then, severe headache, vomiting, and loss of consciousness developed, and a lumbar puncture revealed infiltrations of blasts. Although methotrexate was intrathecally injected, he died due to the respiratory failure. As far as we know, a case of acute megakaryoblastic leukemia with leukemia cutis and meningeal leukemia is quite rare. In addition, it is interesting that megakaryoblastic leukemia was accompanied with both the fibrosis of skin and the myelofibrosis.

Humans↗

Pathogenesis of limb malformations in mice induced by methoxyacetic acid.

The present study was performed to reveal the pathogenesis of limb malformations induced by methoxyacetic acid (MAA) in developing mouse limbs. Pregnant Jcl:ICR mice were orally given at gestational day (gd) 10.5, 11.0, or 11.5 (vaginal plug = gd 0) a single dose of MAA 10 mmol/kg of body weight. Various patterns of cell death in limb buds were observed by vital dye staining with Nile blue A. Under a light microscope and transmission electron microscope, excessive cell death was observed in the mesenchyme as well as in the apical ectodermal ridge (AER) 2 hr after MAA treatment, reaching a maximum after 6 hr. Scanning electron microscopic examinations showed hypoplasia of the AER and small hand plates 24 hr after treatment. Small hand plates and delayed digital ray formation were noted at 48 hr. Neither detachment nor massive necrosis was detected in the periderm covering the limb bud. The distribution of cell death 6 hr after treatment was similar in limb buds treated either at gd 10.5, 11.0 or 11.5, but the final pattern of limb defects was different in fetuses treated at different stages. This study indicates that variations in the pattern of limb defects induced by MAA are due to differences in the amount and distribution of cell death, together with differences in the regenerative capacity of surviving cells.

Abnormalities, Drug-Induced↗

Pattern of limb malformations in mice induced by methoxyacetic acid.

The present study investigated the pattern of limb malformations induced in mice by methoxyacetic acid (MAA), one of di(2-methoxyethyl) phthalate (DMEP) metabolites. Pregnant Jcl:ICR mice were given orally at gestational day (gd) 10.5, 11.0, or 11.5 (vaginal plug = gd 0) a single dose of MAA 10 mmol/kg of body weight. Fetuses were examined at gd 15.5 for external and skeletal malformations. Limb defects were maximum in frequency and severity after administration at gd 11.5. Forelimbs had greater susceptibility than hindlimbs. Treatment at gd 10.5 produced cutaneous or osseous syndactyly between digits I and II, II and III, and ectrodactyly of digit II or digit I. Intercalary defects in the forelimbs were also detected. No hindlimb malformations were induced. Treatment at gd 11.0 induced ectrodactyly of digit II and digit I in the forelimbs, as well as osseous syndactyly or intercalary defects of the metacarpals or phalanges, and the frequency became increased. Hindlimb malformations were also detected in a small number with syndactyly between digits I and II or ectrodactyly in digit I. Treatment at gd 11.5 induced ectrodactyly in the forelimbs. Half of the forelimbs showed ectrodactyly with four missing digits (digits I, II, III, and V) and the remaining limbs showed ectrodactyly with a similar frequency with one, two, or three missing digits, either in the pre- or postaxial area. In the hindlimbs ectrodactyly with one, two, or three missing digits was the most common malformation observed. Syndactyly between digits I and II was also induced in a small percentage.

Abnormalities, Drug-Induced↗

[Usefulness of ulinastatin as a radical scavenger for protection of reperfusion injury after myocardial ischemia in open heart surgery].

The usefulness of ulinastatin for protection of reperfusion injury after myocardial ischemia was evaluated in 25 patients undergone open heart surgery (18 cases with coronary artery bypass grafting and 7 with valve replacements). Twenty five patients were divided into two groups; U (+)-group consisted of 12 patients with ulinastatin (10,000 IU/kg) injected via the aortic root just before aortic declamping, and U (-)-group of 13 patients without ulinastatin. There were no significant differences between the two groups in age, body weight, total cardiopulmonary bypass (CPB) time, and aortic cross clamp time. Blood samples were obtained from coronary sinus before the start of CPB, just before the aortic cross clamp and immediately after reperfusion, and 1 and 3 hours later. Levels of thiobarbituric acid (TBA), alpha-tocopherol (alpha TOC), polymorphonuclear elastase (PMNE), creatine phosphokinase (CK) and creatine phosphokinase isoenzyme (CK-WB) release were measured, and myocardial aerobic metabolism was also evaluated. At each time point after reperfusion, TBA levels in U (+)-group were significantly less (p less than 0.05), and alpha TOC levels were significantly higher (p less than 0.05) than those in U (-)-group. PMNE increased progressively during CPB and showed a peak at 3 hours after reperfusion. And both groups showed increased lactate production and anaerobic metabolism immediately after reperfusion and 1 hour later, as evidenced by changes in excess lactate and redox potential of lactate and pyruvate. There was, however, no significant difference between the two groups with CK-MB as well as CK release.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Artery Bypass↗

Phosphoramidon-sensitive endothelin converting enzyme in rat lung.

A neutral proteinase with endothelin (ET)-1 converting activity was identified in cytosol and membrane fractions prepared from rat lung, in a ratio of 1:4, respectively. The membrane-bound proteinase was solubilized by 0.5% 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) with an increase in specific activity, and then was characterized. The solubilized proteinase was capable of converting big ET-1 to ET-1 with an optimum pH of 6.5, and the conversion was dose-dependently suppressed by phosphoramidon (IC50 = 0.5 microM). The molecular mass of the proteinase was estimated to be about 500 kDa by gel filtration in the presence of 0.5% CHAPS. These results indicate that rat lung contains a phosphoramidon-sensitive neutral proteinase catalyzing conversion of big ET-1 to ET-1. The proteinase may be involved in the biosynthetic pathway of ET-1 in the lung and/or the conversion of circulating big ET-1.

Animals↗

[A ruptured aneurysm in the hypoplastic proximal anterior cerebral artery (A1 portion); case report].

A case of ruptured aneurysm in the hypoplastic proximal anterior cerebral artery (A1 portion) is reported. This 25-years old man complained of the sudden onset of severe headache and vomiting on January 11, 1989. He was referred to our hospital on the same day, and CT scan revealed subarachnoid hemorrhage. Cerebral angiography on the next day revealed an aneurysm in the hypoplastic A1 portion of the right anterior cerebral artery, and no branch was present at the site of the aneurysmal neck. He was operated on using the right pterional approach. The A1 portion was trapped and the aneurysm was removed successfully. The histology of the aneurysm was that of the usual type of the saccular aneurysm. The post-operative course was uneventful. He was discharged with no neurological deficit two months after the operation. As far as we know, there has been no report on a ruptured aneurysm in the hypoplastic A1 portion. We also reviewed the 55 aneurysms in the A1 portion that have been reported in the literature.

Adult↗

Disturbance of refinement of retinotectal projection in chick embryos by tetrodotoxin and grayanotoxin.

The role of neuronal activity in the refinement of the retinotectal projection in chick embryos was studied using tetrodotoxin (TTX) which blocks sodium channels and grayanotoxin I (GTX) which opens the channels. Optic nerve fibers were traced by the fluorescent dye DiI. The toxins were injected into the eyeball during the refinement phase of retinotectal projection (either the 13th, 14th or 15th day of incubation). A tiny crystal of DiI was placed in the temporal part of the retina. In the control embryos, fibers caudally overshooting and arborizations outside the terminal zone were found before maturation of retinotectal projection. Overshooting fibers regressed linearly, and aberrant arborizations reduced quadratically, and then the precise retinotopic map is formed by stage 44 (18th day of incubation). Both TTX and GTX interfered with the regression of overshooting fibers and arborizations outside the terminal zone. The initial action of the toxins are reverse, but their final effect may be comparable, and they may interfere with synchronous firing of the neighboring fibers. Our results emphasize a role of neuronal activity in the refinement of retinotectal projection.

Action Potentials↗

An attempt to structurally convert mu-selective morphine toward delta-receptor binding: dimerization based on enkephalin conformation.

In order to elucidate the substrate specificities for mu- and delta-opioid receptors, dimerization of the mu-specific morphine molecule was attempted, based on the hypothesis of the possible relationship between the molecular conformation of endogenous enkephalin and its selectivity for each opioid receptor. The NOR2 ([normorphine]N-CH2-CH2-N[normorphine]) thus synthesized exhibited agonist activity showing a preference for binding with the delta-opioid receptor, compared with the parent morphine molecule. Antagonist activity was also observed for NOR3 ([normorphine]N-CH2-CH2-CH2-N[normorphine]).

Animals↗

Effects of phorone and/or buthionine sulfoximine on teratogenicity of 5-fluorouracil in mice.

Embryotoxicity and teratogenicity of 5-fluorouracil (5-FU) and modulation of its effect by the depletors of glutathione (GSH) were evaluated in mice. Pregnant ICR mice were intraperitoneally (i.p.) injected with 25 mg/kg of 5-FU on day 11 of gestation (vaginal plug = day 0). Mice were pretreated i.p. with 250 mg/kg of phorone, a GSH depleting agent and/or 200 mg/kg of buthionine sulfoximine (BSO, an inhibitor of GSH biosynthesis) 4 hours before dosing with 5-FU. Dams were killed on day 17 of gestation. Fetuses were examined for external malformations, especially limb malformations. Pretreatment with phorone or BSO decreased fetal weight and increased the frequency and severity of oligodactyly induced by 5-FU, as well as the reduction of maternal GSH levels. Combined use of 125 mg/kg phorone and 100 mg/kg BSO i.p. augmented growth retardation induced with 5-FU. Cotreatment with exogenous GSH, at a dose of 300 mg/kg injected intravenously, could not suppress the augmentative effects of phorone and/or BSO on 5-FU teratogenicity under these experimental conditions. These results indicate that the level of endogenous GSH is one of the factors which significantly affects teratogenicity of 5-FU.

Animals↗

Cerebral energy metabolism in experimental canine hydrocephalus.

Cerebral energy metabolism, its relationship to the stage and extent of hydrocephalus, and the effect of cerebrospinal fluid (CSF) removal on it were studied in experimental canine hydrocephalus produced by intracisternal injection of kaolin by using phosphorus-31 (P-31) magnetic resonance (MR) spectroscopy and MR imaging. P-31 MR spectra were serially obtained before and after CSF removal, maximally on eight occasions over a period of nearly 5 h. There was a decrease in the ratio of creatine phosphate to inorganic phosphate, used as an indicator of the bioenergetic state, in acute and subacute stages of hydrocephalus as compared with the control. An animal in the subacute stage, when periventricular edema was most prominent, exhibited the most predominent decrease in this ratio at 14 days after hydrocephalic insult. The recovery of the ratio toward the control level was seen in the chronically hydrocephalic animal. There was no change in adenosine triphosphate (ATP) levels in any stage of hydrocephalus. Serial spectra obtained after the withdrawal of ventricular CSF showed no change in the bioenergetic state of the brain in any stage of hydrocephalus. There was no relationship between either the extent of hydrocephalus or the ventricular CSF pressure and the change in the bioenergetic state or the levels of any of the phosphorus compounds. These findings may indicate the alteration of the mitochondrial energy metabolism in hydrocephalus, which may explain the mechanism of hydrocephalic syndrome.

Acute Disease↗

The specificity of antiglobulin autoantibodies in patients with primary Sjögren's syndrome.

Antiglobulin autoantibodies have already been demonstrated in the sera of patients with primary Sjögren's syndrome (primary SS). In our study, the specificity of primary SS antiglobulins for different regions of IgG molecules was examined by employing both direct binding and competitive inhibition enzyme-linked immunosorbent assay. We found that a considerable amount of total antiglobulins in primary SS was specific for the Fab portion, although the remainder was specific for the Fc portion, namely rheumatoid factor (RF). In contrast, most of the antiglobulins in RA were specific for the Fc portion of IgG. These results indicate that in primary SS, antiglobulins directed against epitopes different from those of RF are produced. These antiglobulins may prove to have a different role in primary SS than that ascribed to RF in RA.

Antibodies, Anti-Idiotypic↗