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Biomedical subjects

M Matsunaga

Publications and source records attributed to M Matsunaga.

At least 19 recordsLinked to original sources

Controlled normothermia during ischemia is important for the induction of neuronal cell death after global ischemia in mouse.

A stable model of neuronal damage after ischemia is needed in mice to enable progression of transgenic strategies. We performed transient global ischemia induced by common carotid artery occlusions with and without maintaining normal rectal temperature (Trec) in order to determine the importance of body temperature control during ischemia. We measured brain temperature (Tb) during ischemia/reperfusion. Mice with normothermia (Trec within +/- 1 degrees C) had increased mortality and neuronal cell death in the CA1 region of hippocampus, which did not occur in hypothermic animals. If the Trec was kept within +/- 1 degrees C, the Tb decreased during ischemia. After reperfusion, Tb in the normothermia group developed hyperthermia, which reached > 40 degrees C and was > 2 degrees C higher than Trec. We suggest that tightly controlled normothermia and prevention of hypothermia (Trec) during ischemia are important factors in the development of a stable neuronal damage model in mice.

Animals↗

Post-challenge hyperinsulinaemia rather than hyperglycaemia is associated with the severity of coronary artery disease in patients without a previous diagnosis of diabetes mellitus.

OBJECTIVE: To ascertain the prevalence of abnormal glucose metabolism in patients with coronary artery disease (CAD) but no previous diagnosis of diabetes mellitus (DM) and to examine the relation between the severity of CAD and responses of glucose and insulin to the glucose tolerance test. METHODS AND RESULTS: Abnormalities of glucose metabolism and insulin response were analysed in 144 patients with CAD without a previous diagnosis of DM who underwent both coronary arteriography and 75 g oral glucose tolerance test. The proportions of impaired and diabetic glucose tolerance were very high (39% for impaired and 21% for diabetic glucose tolerance); only 40% had normal glucose tolerance. The parameters of glucose metabolism were not associated with the number of diseased coronary arteries or the presence of previous myocardial infarction (MI). However, the insulin concentration at 60 minutes or 120 minutes after glucose challenge, insulin area, and the ratio of insulin to glucose area were significantly higher in patients with significant coronary stenosis and with previous MI. Fasting glucose concentration and most conventional risk factors did not predict post-challenge hyperinsulinaemia. CONCLUSION: Patients with CAD without a previous diagnosis of DM had a high prevalence of abnormal glucose tolerance. Post-challenge hyperinsulinaemia was associated with the number of diseased coronary arteries and the presence of previous MI. The insulin response to the glucose challenge test requires further investigation as a potential risk factor for CAD and a potential target for intervention.

Blood Glucose↗

Suppression of oxidative stress after transient focal ischemia in interleukin-1 knock out mice.

Interleukin-1 (IL-1) contributes to ischemic neurodegeneration. However, the mechanisms regulating action of IL-1 are still poorly understood. In order to clarify this central issue, mice that were gene deficient both IL-1alpha and beta (IL-1 KO) and wild-type mice were subjected to 1 hour transient middle cerebral artery occlusion (tMCAO). The concentration of 8-hydroxy deoxyguanosine (8OHdG) which is considered to be a reliable oxidative DNA damage by superoxide anion, in brain and of total nitric oxide (NO) in plasma were determined by use of HPLC. Twenty-four hours after tMCAO, the ratio of 8OHdG to dG in the ipsilateral hemisphere of wild-type mice were 2.24 x 10(-3) and 4.41 x 10(-3) in the neocortex and striatum, respectively. The concentration of 8OHdG in the ipsilateral hemisphere of the wild-type mice was higher than that of the IL-1 KO mice. The concentration of total NO in the plasma of IL-1 KO mice was also lower than that of the wild-type 24 hours after tMCAO. These results strongly suggest that IL-1 is participated in generating reactive oxygen spices and it aggravates and induces the ischemic neuronal cell death.(183 words).

8-Hydroxy-2'-Deoxyguanosine↗

Effect of continuous low-dose intravenous diltiazem on epidural fentanyl analgesia after lower abdominal surgery.

BACKGROUND: The postoperative opioid-sparing effects of systemic L-type calcium channel blockers are controversial. We investigated whether the postoperative analgesic effect of epidural fentanyl was enhanced by i.v. infusion of diltiazem at a rate that would minimize any cardiovascular depressant effect. METHODS: After elective lower abdominal gynaecological surgery, 30 patients were randomized to receive continuous i.v. diltiazem 1 micro g kg(-1) min(-1) (diltiazem group) or the same volume of saline (control group) for 24 h. Cumulative postoperative epidural fentanyl consumption, visual analogue scale (VAS) scores and verbal rating scores (VRS) at rest and during mobilization, sedation scores, incidence of side-effects and overall patient satisfaction were assessed. RESULTS: There was no significant difference in cumulative epidural fentanyl consumption between the groups at any period. Although there were no statistically significant differences in VAS scores, VRS, sedation scores, incidence of side-effects and overall patient satisfaction, there was a trend to an increased incidence of nausea in the diltiazem group. CONCLUSIONS: Continuous i.v. infusion of diltiazem did not reduce epidural fentanyl consumption when administered at dosages having minimal haemodynamic depressant effects.

Analgesia, Epidural↗

Dipole orientation differs between high frequency oscillations and N20m current sources in human somatosensory evoked magnetic fields to median nerve stimulation.

The dipole orientation of equivalent current source for the high frequency oscillations (HFOs) above 300 Hz and that for the underlying N20m were compared. Somatic magnetic fields were recorded over the left hand somatosensory area to right median nerve stimulation at the wrist with a wide-bandpass (0.1-2000 Hz). The HFOs and underlying N20m were extracted by digital filtering of 300-900 Hz and 1-300 Hz, respectively. We found that the orientation of the HFOs and underlying N20m current sources differs and that the HFO source orientation shows a more divergent pattern than the N20m. These results suggest that the somatosensory HFOs are not generated from the pyramidal cell population in area 3b which produces the underlying N20m and that they may reflect activities of the non-pyramidal neuron population.

Adult↗

Expression of metabotropic glutamate receptor mRNAs in the human spinal cord: implications for selective vulnerability of spinal motor neurons in amyotrophic lateral sclerosis.

To elucidate the relevance of metabotropic glutamate receptors (mGluRs) to the selective vulnerability of motor neurons in the spinal cord in patients with amyotrophic lateral sclerosis (ALS), we investigated the distribution of mRNAs coding mGluR1-5 in the normal human spinal cord. The mRNAs for mGluR1, 4 and 5 were observed in the spinal gray matter, whereas mGluR2 mRNA was absent in the spinal cord and mGluR3 mRNA was displayed only on glial cells in the white matter. Signals for mGluR1 and mGluR5 were enriched in the dorsal horn, while mGluR4 mRNA was abundant in the ventral horn. Since agonists to group I mGluRs (mGluR 1 and 5) have been demonstrated to have neuroprotective effects on spinal motor neurons, less expression of mRNAs coding mGluR1 and mGluR5 in the ventral horn than in the dorsal horn may be implicated in the selective susceptibility of spinal motor neurons in ALS.

Aged↗

Fluoxetine reduces L-DOPA-derived extracellular DA in the 6-OHDA-lesioned rat striatum.

We investigated the effect of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on L-DOPA-derived extracellular dopamine (DA) levels in the striatum of rats with nigrostriatal dopaminergic denervation using in vivo microdialysis. Treatment with fluoxetine (10 mg/kg, i.p.) induced a 41% reduction in the cumulative amount of extracellular DA during 300 min following L-DOPA administration (50 mg/kg, i.p.; p < 0.01). This effect was antagonized by pretreatment with WAY-100635, a potent 5-HT1A antagonist, indicating that this effect of fluoxetine is due to its indirect 5-HT1A agonistic property. These results suggest that SSRIs may impair motor functions in patients with Parkinson's disease by reducing efflux of exogenous L-DOPA-derived DA.

Adrenergic Agents↗

Expression and localization of cytochrome P450 17 alpha-hydroxylase/c17,20-lyase in the avian brain.

Steroids synthesized de novo from cholesterol in the brain are generally called neurosteroids. We have recently demonstrated, using biochemical and molecular biological methods, that certain structures in the quail brain possess cytochrome P450 side-chain cleavage enzyme (P450scc) and 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase (3beta-HSD) and produce pregnenolone, pregnenolone sulfate and progesterone. To clarify the biosynthetic pathway of neurosteroids in the avian brain, therefore, we examined the expression of messenger RNA (mRNA) encoding for the enzyme cytochrome P450 17alpha-hydroxylase/c17,20-lyase (P450(17alpha,lyase)), which converts pregnenolone to dehydroepiandrosterone via 17alpha-hydroxypregnenolone or progesterone to androstenedione via 17alpha-hydroxyprogesterone. RT-PCR analysis followed by Southern hybridization indicated the expression of P450(17alpha,lyase) mRNA in the brain of sexually mature birds without a clear-cut sex difference. Employing biochemical techniques combined with HPLC analysis, the conversion of progesterone to 17alpha-hydroxyprogesterone was also found in brain slices of the mature male. P450(17alpha,lyase) mRNA was detected in various brain regions, but there was a clear regional difference in the expression. The expressions of P450(17alpha,lyase) mRNA in the diencephalon and mesencephalon were significantly higher than those in the cerebrum and cerebellum, unlike 3beta-HSD mRNA, which showed no regional difference in the expression. In situ hybridization revealed the cellular localization of P450(17alpha,lyase) mRNA. The cells expressing P450(17alpha,lyase) mRNA were detected several diencephalic and mesencephalic regions, such as the preoptic area, the anterior hypothalamus, the dorsolateral thalamus, the optic tectum and the ventral midbrain. The expression was also localized in the septum, the hyperstriatum accessorium, and the ventral portions of the archistriatum in the telencephalon. Cerebellar Purkinje cells also expressed P450(17alpha,lyase) mRNA. These results suggest that the avian brain possesses P450(17alpha,lyase) as well as P450scc and 3beta-HSD in both sexes. The expression of P450(17alpha,lyase) in the avian brain may be region-dependent.

17-Hydroxysteroid Dehydrogenases↗

Combined transcriptome and proteome analysis as a powerful approach to study genes under glucose repression in Bacillus subtilis.

We used 2D protein gel electrophoresis and DNA microarray technologies to systematically analyze genes under glucose repression in B:acillus subtilis. In particular, we focused on genes expressed after the shift from glycolytic to gluconeogenic at the middle logarithmic phase of growth in a nutrient sporulation medium, which remained repressed by the addition of glucose. We also examined whether or not glucose repression of these genes was mediated by CcpA, the catabolite control protein of this bacterium. The wild-type and ccpA1 cells were grown with and without glucose, and their proteomes and transcriptomes were compared. 2D gel electrophoresis allowed us to identify 11 proteins, the synthesis of which was under glucose repression. Of these proteins, the synthesis of four (IolA, I, S and PckA) was under CcpA-independent control. Microarray analysis enabled us to detect 66 glucose-repressive genes, 22 of which (glmS, acoA, C, yisS, speD, gapB, pckA, yvdR, yxeF, iolA, B, C, D, E, F, G, H, I, J, R, S and yxbF ) were at least partially under CcpA-independent control. Furthermore, we found that CcpA and IolR, a repressor of the iol divergon, were involved in the glucose repression of the synthesis of inositol dehydrogenase encoded by iolG included in the above list. The CcpA-independent glucose repression of the iol genes appeared to be explained by inducer exclusion.

Amino Acid Sequence↗

Activation of 5-HT(1A) but not 5-HT(1B) receptors attenuates an increase in extracellular dopamine derived from exogenously administered L-DOPA in the striatum with nigrostriatal denervation.

In order to determine whether L-DOPA-derived extracellular dopamine (DA) in the striatum with dopaminergic denervation is affected by activation of serotonin autoreceptors (5-HT(1A) and 5-HT(1B) receptors), we applied in vivo brain microdialysis technique to 6-hydroxydopamine-lesioned rats and examined the effects of the selective 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the selective 5-HT(1B) receptor agonist CGS-12066 A on L-DOPA-derived extracellular DA levels. Single L-DOPA injection (50 mg/kg i.p.) caused a rapid increase and a following decrease of extracellular DA, with a peak value at 100 min after L-DOPA injection. Pretreatment with both 0.3 mg/kg and 1 mg/kg 8-OH-DPAT (i.p.) significantly attenuated an increase in L-DOPA-derived extracellular DA and the times of peak DA levels were prolonged to 150 min and 225 min after L-DOPA injection, respectively. These 8-OH-DPAT-induced changes in L-DOPA-derived extracellular DA were antagonized by further pretreatment with WAY-100635, a selective 5-HT(1A) antagonist. In contrast, intrastriatal perfusion with the 5-HT(1B) agonist CGS-12066 A (10 nM and 100 nM) did not induce any changes in L-DOPA-derived extracellular DA. Thus, stimulation of 5-HT(1A) but not 5-HT(1B) receptors attenuated an increase in extracellular DA derived from exogenous L-DOPA. These results support the hypothesis that serotonergic neurons are primarily responsible for the storage and release of DA derived from exogenous L-DOPA in the absence of dopaminergic neurons.

Animals↗

Mutation of an arginine biosynthesis gene causes reduced pathogenicity in Fusarium oxysporum f. sp. melonis.

Restriction enzyme-mediated integration (REMI) mutagenesis was used to tag genes required for pathogenicity of Fusarium oxysporum f. sp. melonis. Of the 1,129 REMI transformants tested, 13 showed reduced pathogenicity on susceptible melon cultivars. One of the mutants, FMMP95-1, was an arginine auxotroph. Structural analysis of the tagged site in FMMP95-1 identified a gene, designated ARG1, which possibly encodes argininosuccinate lyase, catalyzing the last step for arginine biosynthesis. Complementation of FMMP95-1 with the ARG1 gene caused a recovery in pathogenicity, indicating that arginine auxotrophic mutation causes reduced pathogenicity in this pathogen.

Arginine↗

Optimization of conditions for detailed compositional analysis of acrylic oligomers by supercritical fluid chromatography with temperature programming or modifier gradient technique.

Acrylic oligomers such as pentaerythritolacrylates (PEA), which are often utilized in the field of functionalized materials, generally consist of very complex homologous series. In this work, measuring conditions for packed-column supercritical fluid chromatographic separation of a complex PEA sample manufactured industrially were systematically examined using temperature programming or modifier gradient technique. Under the conditions thus optimized, not only the main components, PEA homologues containing different number of acryloyl groups, but also trace constituents such as their by-products formed through Michael addition reactions were favorably resolved on the resulting chromatograms. The fact that the coefficient of variation (CV) for relative intensity of each peak was approximately 3-6% even for the minor components suggested that detailed compositional analysis of PEAs could be performed precisely by the proposed method.

Journal Article↗

[Recurrence of bullous pemphigoid after surgery: report of a case].

We report a 38-year-old woman with myoma uteri and bullous pemphigoid controlled by oral prednisolone (7.5 mg.day-1). She underwent transabdominal hysterectomy under epidural anesthesia using mepivacaine supplemented with intravenous midazolam and butorphanol, without untoward event. On the postoperative day 2, recurrence of bullous pemphigoid was noted. The skin lesion of pemphigoid was improved after increasing the prednisolone dose up to 60 mg a day.

Adult↗

[A case of acute sensory neuropathy associated with cytomegalovirus infection].

We report a non-compromised patient with acute sensory neuropathy (ASN) developed following cytomegalovirus (CMV) hepatitis. A 67-year-old man admitted to a hospital because of acute hepatic dysfunction accompanying fever and skin eruption. One month later, when hepatic function normalized, numbness and clumsiness started acutely first in the right upper limb next to all the extremities. He found difficulty in walking in a couple of weeks. One month after the commencement of neurological illness, he was referred to us. On examination, he had sensory limb ataxia. His gait was wide-based, and Romberg sign was positive. Position sense was severely diminished in the extremities. Skin sensation was also attenuated distally, while no motor weakness was noted. Tendon reflexes were almost absent. Nerve conduction studies revealed absent sensory potentials in all but the left median nerve, in which amplitude was 5.5 microV with sensory conduction velocity of 40.7 m/s. Motor conduction studies, on the other hand, appeared normal except for a slight focal delay in the right ulnar nerve across the elbow. Mild increase in F-wave latencies was noted. A sural nerve specimen taken two months after the neurological onset showed a marked decrease in myelinated fiber density and active fiber degenerations accompanying axonal sproutings. Sjögren syndrome and paraneoplastic neuropathy were excluded serologically and by comprehensive imaging techniques. Although IgM anti-CMV antibody was not detected, serum IgG anti-CMV antibody was positive and significantly increased during the neurological illness. The intrathecal antibody synthesis of IgG anti-CMV antibody was suggested by a low serum/cerebrospinal fluid (CSF) antibody ratio and a high CSF IgG index. From these observations, it was strongly suggested that acute hepatitis and subsequent ASN were associated with CMV infection in this patient. Although some cases with post-infectious ASN have been previously reported, this is the first report of ASN preceded by CMV infection.

Acute Disease↗

Magnetic Effects on Alkylammonium Chloride Solutions Investigated by Interfacial Tension Measurements at the Mercury/Solution Interface.

The effects of magnetic exposure on several kinds of alkylammonium chloride solutions were investigated using interfacial tension measurements at the mercury/solution interface. The comparison between the electrocapillary curves of magnetized and nonmagnetized solutions revealed that magnetic exposure induced an increase in interfacial tension, and that such an effect was remarkable at around the potential of zero charge. The appearance of the magnetic effect depended on the specific adsorbability of alkylammonium cations, which in turn depended on the kind of cations. The interfacial tension change induced by magnetic exposure quantitatively correlated with the specific adsorbability of the cations. These results indicated that the magnetism induced an effect on the solution of alkylammonium cations having higher specific adsorbabilities. Copyright 2000 Academic Press.

Journal Article↗

Peripheral and central conduction abnormalities in diabetes mellitus.

OBJECTIVES: To investigate peripheral and central somatosensory conduction in patients with diabetes. METHODS: The authors recorded sensory nerve action potentials and 5-channel somatosensory evoked potentials (SEPs) with noncephalic reference after median nerve stimulation in 55 patients with diabetes and 41 age- and height-matched normal subjects. The authors determined onset or peak latencies of the Erb's potential (N9) and the spinal N13-P13 and the cortical N20-P20 components, and obtained the central conduction time (CCT) by onset-to-onset and peak-to-peak measurements. RESULTS: Both onset and peak latencies of all SEP components were prolonged in patients with diabetes. The mean onset CCT in the diabetic group was 6.3 +/- 0.5 msec (mean +/- SD)-significantly longer than that in the control group (6.1 +/- 0.2 msec)-whereas no significant difference was found in the peak CCT. The amplitudes of N9 and N13-P13 components (but not N20-P20) were significantly smaller in the diabetic group. The peripheral sensory conduction velocity was also decreased in the diabetic group, but there was no significant correlation between peripheral conduction slowing and the onset of CCT prolongation. CONCLUSIONS: Diabetes affects conductive function in the central as well as peripheral somatosensory pathways. The CCT abnormality does not coincide with lowering of the peripheral sensory conduction. The current results do not favor a hypothesis that a central-peripheral distal axonopathy plays an important role in development of diabetic polyneuropathy.

Adult↗