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Biomedical subjects

S Aoki

Publications and source records attributed to S Aoki.

At least 91 records · Page 5Linked to original sources

[Study of lymphocyte and NK cell activity during mild hypothermia therapy].

Infectious disease is a common complication of mild hypothermia therapy. However, very little has been reported about immune response during hypothermia. In the present study, the number and subset of peripheral lymphocytes and mitogen response to phytohaemagglutinin (PHA) and concanavalin A (Con-A) were examined in 14 patients who received mild hypothermia therapy. NK cell ratio and activity were also examined in the same patients. Six out of 14 patients had complicated infectious diseases during mild hypothermia therapy. Five of them had pneumonia and the remaining one had thrombophlebitis. The number of peripheral lymphocytes decreased in patients whose rectal temperature was less than 34.5 degrees C, whereas mitogen response of lymphocytes to PHA and Con-A remained unchanged in patients whose rectal temperature was above 34.0 degrees C. NK cell ratio and cytotoxicity decreased in patients whose rectal temperature was less than 34.5 degrees C, including infectious cases. These results suggested that, under hypothermia therapy, immune responses of the patients whose rectal temperature was less than 34.5 degrees C were disturbed because of the reduced number of peripheral lymphocytes and depression of NK cell activity.

Adult↗

[Three cases of malignant lymphoma accompanied by renal cell carcinoma].

Three cases of malignant lymphoma (ML) accompanied by renal cell carcinoma (RCC) are reported. From September 1997 through August 2000, we treated 85 patients with ML. Among these patients, three had accompanying RCC (clear cell type): case 1, a 57-yr-old man with gamma/delta-T cell lymphoma; case 2, a 25-yr-old man with Grade 3 follicular lymphoma; case 3, a 64-yr-old man with MALToma of the right orbit. Renal cell carcinoma is a relatively rare disease, but several reports have indicated that, for some reason, the incidence of concurrent RCC and ML is higher than expected. It is possible that the two malignancies share some common background factors, such as genetic mutation, immunological abnormality, or an immunomodulatory effect of the first tumor. The patient in case 2 was thought to have an abnormal immunological background from his medical history, which included bronchial asthma, idiopathic thrombocytopenic purpura, and mesangial proliferative glomerulonephritis (non-IgA type). Therefore the combination of ML and RCC in this patient may have been due to immunological impairment.

Adult↗

Neuropsychological changes after surgical treatment for temporal lobe epilepsy.

PURPOSE: The effect of unilateral temporal lobectomy on seizure frequency is well recognized, but little is known about the neuropsychological changes that occur after surgical treatment. We assessed neuropsychological status in 26 patients with an average age of 35 years before and after unilateral temporal lobectomy for medically intractable TLE. METHODS: Neuropsychological examination to assess cognitive function, memory, attention, visuospatial analysis, language, and emotional functions was performed preoperatively and at 1 month and 1 year after the surgery. RESULTS: At both 1 month and 1 year after the surgery, the patients had improved scores, compared with the preoperative scores, on the Wechsler Adult Intelligence Scale-Revised (WAIS-R: verbal IQ, performance IQ, and full-scale IQ), Wechsler Memory Scale-Revised (WMS-R: verbal, general, and delayed paired associates memory), and Raven Colored Progressive Matrices. In the Minnesota Multiphasic Personality Inventory (MMPI), significant decreases were observed at 1 year after the surgery in the scores for infrequency, hypochondriasis, psychasthenia, and schizophrenia. Patients in whom the seizures had been relieved postoperatively also had improved scores on the WAIS-R, WMS-R, and Raven Colored Progressive Matrices. CONCLUSIONS: These data suggest that neuropsychological improvement postoperatively is influenced by the reduction in the frequency of seizures after surgery.

Adult↗

[The false positive reaction of the Triage panel drug-of-abuse by herbal drugs ma-huang (Ephedra sinica (Ephedraceae))].

We investigated false-positive reactions obtained from a drug screening test using a Triage panel. We detected 2 cases giving false-positive reaction for AMP (amphetamine, methamphetamine) during the screening of 187 normal subjects. Subsequent follow up testing by high-performance liquid chromatography (HPLC), showed both to be false-positive reactions. As both cases have a history of ingesting the herbal drug, Ma-huang (Ephedra sinica (Ephedraceae)), containing ephedrine, we examined the relationship between false-positive reactions on Triage and Ma-huang. All urine samples collected from 7 healthy volunteers following administration of Ma-huang indicated AMP positive on Triage. Also a high ratio of AMP positives was observed in the patients who were administered Ma-huang-containing drugs at the hospital. However, none of them were identified as true-positives by HPLC or gas chromatography mass spectrometry (GC/MS) analysis. The extract of Ma-huang contained in herbal drugs, which otherwise contain neither amphetamine nor its derivatives, gives (AMP) positive indications on Triage. We speculate that unidentified components of Ma-huang cause the false-positive reactions. We suggest that follow-up tests by GC/MS or HPLC are needed wherever a positive result is obtained from a screening test by Triage. Furthermore, it will be established to continue collecting information on prescribed and non-prescribed drugs.

Adult↗

[The ubiquitin-proteasome system and neurodegeneration].

Many studies have suggested the ubiquitin-proteasome system played an essential role in the pathogenesis of neurodegenerative disorders. In 1999, we provided evidence that a mutation of the system could directly cause neurodegeneration using the gad mouse. Namely, we identified the gad mutation was caused by an intragenic deletion of a gene encoding ubiquitin C-terminal hydrolase 1(UCH-L1), which is a member of de-ubiquitinating enzyme family. In human, missense mutation of UCH-L1 gene was reported in a German family with Parkinson's disease. As well, the parkin gene product was revealed to be an E3 ubiquitin ligase which recognize a form of alpha-synuclein as a substrate. Thus, the investigation of the ubiquitin-proteasome system should provide a clue for understanding neurodegeneration. We have characterized UCH-L1 and identified candidates of endogenous substrates as well as interacting proteins of UCH-L1. In addition, we found amount of monomeric ubiquitin was decreased in the brain of the gad mouse compared with wild type mice. We have also tried to develop "protein therapy" using UCH-L1 protein with TAT sequence. We observed the protein was delivered to brain after intraperitoneal injection in the wild type mouse. This approach would provide a new therapeutic strategy for neurodegeneration.

Animals↗

Dynamical quark effects on light quark masses

Light quark masses are calculated in lattice QCD with two degenerate flavors of dynamical quarks. The calculations are made with improved actions with lattice spacing a = 0.22-0.11 fm. In the continuum limit we find m(M&Smacr;)(ud)(2 GeV) = 3.44(+0.14)(-0.22) MeV using the pi and rho meson masses as physical input, and m(M&Smacr;)(s)(2 GeV) = 88(+4)(-6) MeV or 90(+5)(-11) MeV with the K or straight phi meson mass as additional input. The quoted errors represent statistical and systematic combined, the latter including those from continuum and chiral extrapolations, and from renormalization factors. Compared to quenched results, two flavors of dynamical quarks reduce quark masses by about 25%.

Journal Article↗

Roles of His-79 and Tyr-180 of D-xylose/dihydrodiol dehydrogenase in catalytic function.

Mammalian dimeric dihydrodiol dehydrogenase is identical with d-xylose dehydrogenase and belongs to a protein family with prokaryotic proteins including glucose-fructose oxidoreductase. Of the conserved residues in this family, either His-79 or Tyr-180 of d-xylose/dihydrodiol dehydrogenase has been proposed to be involved in the catalytic function. Site-directed mutagenesis was used to examine the roles of the two residues of the monkey enzyme. A mutant, Y180F, was almost inactive, but, similarly to the wild-type enzyme, exhibited high affinity for NADP(H) and fluorescence energy transfer upon binding of NADPH. The H79Q mutation had kinetically largest effects on K(d) (>7-fold increase) and K(m) (>25-fold increase) for NADP(H), and eliminated the fluorescence energy transfer. Interestingly, the dehydrogenase activity of this mutant was potently inhibited with a 190-fold increase in the K(m) for NADP(+) by high ionic strength, which activated the activity of the wild-type enzyme. These results suggest a critical role of Tyr-180 in the catalytic function of this class of enzymes, in addition to functions of His-79 in the coenzyme binding and chemical steps of the reaction.

Animals↗

The roles of Rirol and Ngrol genes in hairy root induction in Nicotiana debneyi.

The function of Rirol genes in TL-DNA of the Ri plasmid of Agrobacterium rhizogenes has been previously studied in Nicotiana tabacum and Daucus carota, but it was reported that these plants have a TL-DNA-similar sequence in their genome. We investigated the function of Rirol genes in N. debneyi by infection with A. tumefaciens harboring these genes, because the genome of N. debneyi does not contain a TL-DNA-similar sequence. The single gene RirolB induced adventitious roots in N. debneyi. Introduction of a DNA fragment that contained RirolB, RirolC, RiORF13 and RiORF14 resulted in more intense and earlier root formation than that of RirolB. Ngrol genes (NgrolB, NgrolC, NgORF13, and NgORF14) in the genome of Nicotiana glauca that are similar in sequence to Rirol genes were also examined. In contrast with Rirol genes, Ngrol genes did not induce adventitious roots on leaf segments of N. debneyi. Further infection analysis revealed that one of the reasons for this diversity of their functions might be the difference in the rolB region between the sequence of bacteria and plants. The difference in function between the genes of plants and bacteria is analyzed and the molecular evolution of Ngrol genes is discussed.

Journal Article↗

Functional comparison between YCF1 and MRP1 expressed in Sf21 insect cells.

YCF1 is a yeast vacuole membrane transporter involved in resistance to Cd(2+) and to exogenous glutathione S-conjugate precursors. MRP1 contributes to multidrug resistance (MDR) in tumor cells. MRP1 and YCF1 have extensive amino acid sequence homology (63% amino acid similarity). We expressed MRP1 or YCF1 in insect cell membranes and compared their functions to know more about their structure-function relationships. YCF1 and MRP1 with His epitopes were expressed in Sf21 insect cells; both of them in the plasma membrane. The ATP-dependent transport of [(3)H]LTC(4) in Sf/YCF1-His vesicles was osmotically sensitive and showed saturable kinetics with an apparent K(m) of 758 nM for LTC(4) and 94 microM for ATP which were similar to those in yeast cells. The K(m) of YCF1 for LTC(4) (758 nM) was sevenfold higher than that of MRP1 (108 nM). MK-571 and ONO-1078, reversing agents for MRP1-mediated MDR, considerably inhibited the transport of LTC(4) by both YCF1 and MRP1. However, PAK-104P, a pyridine analog that reverses MDR associated with P-gp and MRP1, inhibited the transporting activity of MRP1 stronger than that of YCF1. KE1, another MDR reversing agent, moderately inhibited the transport of LTC(4) by MRP1 but not that of YCF1. In conclusion, we successfully expressed yeast YCF1 in Sf21 insect cells and found that the localization of the protein was different from that in yeast. The function of YCF1 in Sf21 insect cells was similar but not identical to that of MRP1.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Damage-induced neuronal endopeptidase (DINE) is a unique metallopeptidase expressed in response to neuronal damage and activates superoxide scavengers.

We isolated a membrane-bound metallopeptidase, DINE (damage-induced neuronal endopeptidase), by differential display PCR using rat normal and axotomized hypoglossal nuclei. The most marked properties of DINE were neuron-specific expression and a striking response to axonal injury in both the central nervous system and peripheral nervous system. For instance, cranial and spinal nerve transection, ischemia, corpus callosum transection, and colchicine treatment increased DINE mRNA expression in the injured neurons, whereas kainate-induced hyperexcitation, immobilization, and osmotic stress failed to up-regulate DINE mRNA. Expression of DINE in COS cells partially inhibited C2-ceramide-induced apoptosis, probably because of the activation of antioxidant enzymes such as Cu/Zn-superoxide dismutase, Mn-superoxide dismutase, and glutathione peroxidase through the proteolytic activity of DINE. These data provide insight into the mechanism of how injured neurons protect themselves against neuronal death.

Animals↗

A strong source of methyl chloride to the atmosphere from tropical coastal land.

Methyl chloride (CH3Cl), the most abundant halocarbon in the atmosphere, has received much attention as a natural source of chlorine atoms in the stratosphere. The annual global flux of CH3Cl has been estimated to be around 3.5 Tg on the grounds that this must balance the loss through reaction with OH radicals (which gives a lifetime for atmospheric CH3Cl of 1.5 yr). The most likely main source of methyl chloride has been thought to be oceanic emission, with biomass burning the second largest source. But recent seawater measurements indicate that oceanic fluxes cannot account for more than 12% of the estimated global flux of CH3Cl, raising the question of where the remainder comes from. Here we report evidence of significant CH3Cl emission from warm coastal land, particularly from tropical islands. This conclusion is based on a global monitoring study and spot measurements, which show enhancement of atmospheric CH3Cl in the tropics, a close correlation between CH3Cl concentrations and those of biogenic compounds emitted by terrestrial plants, and OH-linked seasonality of CH3Cl concentrations in middle and high latitudes. A strong, equatorially located source of this nature would explain why the distribution of CH3Cl is uniform between the Northern and Southern hemispheres, despite their differences in ocean and land area.

Arctic Regions↗

Quenched light hadron spectrum

We present results of a large-scale simulation for the flavor nonsinglet light hadron spectrum in quenched lattice QCD with the Wilson quark action. Hadron masses are calculated at four values of lattice spacing in the range a approximately 0.1-0.05 fm on lattices with a physical extent of 3 fm at five quark masses corresponding to m(pi)/m(rho) approximately 0.75-0.4. The calculated spectrum in the continuum limit shows a systematic deviation from experiment, though the magnitude of deviation is contained within 11%. Results for decay constants and light quark masses are also reported.

Journal Article↗

Mapping of a particular element using an absorption edge with an X-ray fluorescence imaging microscope.

An X-ray fluorescence imaging microscope with a Wolter-type objective mirror (magnification: 13) has been constructed at beamline 39XU of SPring-8. Monochromatic X-rays (DeltaE/E approximately 10(-4)) in the energy range 6-10 keV were used for X-ray fluorescence excitation of the specimens. Using two monochromatic X-rays above and below the absorption edge of a particular element, a two-dimensional image of the element could be obtained. As a result, two-dimensional element mapping of the test specimens (Cu, Co, Ni, Fe and Ti wires) and constituent minerals (Fe, Mn and Ti) of a rock specimen (a piemontite-quartz schist) became possible.

Journal Article↗

Two-dimensional thick-slice MR digital subtraction angiography for assessment of cerebrovascular occlusive diseases.

Although spatial resolution of current MR angiography is excellent, temporal resolution has remained unsatisfactory. We evaluated clinical applicability of 2D thick-slice, contrast-enhanced subtraction MR angiography (2D-MR digital subtraction angiography) with sub-second temporal resolution in cerebrovascular occlusive diseases. Twenty-five patients with cerebrovascular occlusive diseases (8 moyamoya diseases, 10 proximal internal carotid occlusions, and 2 sinus thromboses ) were studied with a 1.5-T MR unit. The MR digital subtraction angiography (MRDSA) was performed per 0.97 s continuously just after a bolus injection of 15 ml of gadolinium chelates up to 40 s in sagittal (covering hemisphere) or coronal planes. Subtraction images were generated at a workstation. We evaluated imaging quality and hemodynamic information of MRDSA in comparison with those of routine MR imaging, non-contrast MR angiography, and X-ray intra-arterial DSA. Major cerebral arteries, all of the venous sinuses, and most tributaries were clearly visualized with 2D MRDSA. Also, pure arterial phases were obtained in all cases. The MRDSA technique demonstrated prolonged circulation in sinus thromboses, distal patent lumen of proximal occlusion, and some collateral circulation. Such hemodynamic information was comparable to that of intra-arterial DSA. Two-dimensional thick-slice MRDSA with high temporal resolution has a unique ability to demonstrate cerebral hemodynamics equivalent to that of intra-arterial DSA and may play an important role for evaluation of cerebrovascular occlusive diseases.

Adult↗

Time-resolved two-dimensional thick-slice magnetic resonance digital subtraction angiography in assessing brain tumors.

The aim of this study was to evaluate clinical applicability of two-dimensional (2D) thick-slice, contrast-enhanced magnetic resonance digital subtraction angiography (MRDSA) with high temporal resolution in diagnosis of brain tumors. Forty-four patients with brain tumors including, 15 meningiomas, 8 gliomas, 6 metastatic tumors, 4 neuromas, and 2 hemangioblastomas, were studied with 2D MRDSA with frame rate approximately 1 s. Images were continuously obtained following the initiation of bolus injection of gadolinium chelates for 40 s and subtraction images were generated in a workstation. We evaluated visualization of normal cranial vessels on MRDSA and compared MRDSA and intra-arterial digital subtraction angiography (IADSA) with regard to hemodynamic information. Large cerebral arteries, all venous sinuses, and most tributaries were clearly visualized. A stain was present in hypervascular tumors including all 15 meningiomas and 2 hemangioblastomas on MRDSA. Presence of a stain demonstrated on MRDSA and that on IADSA coincided in 16 of 20 cases (Spearman rank correlation value was 0.85). The location, shape, and phase of the stain on MRDSA were similar to those on IADSA. Two-dimensional MRDSA with high temporal resolution has a unique ability to demonstrate cerebral hemodynamics, such as IADSA, and can play an important role in assessing brain tumors.

Adolescent↗

Simultaneous display of MRA and MPR in detecting vascular compression for trigeminal neuralgia or hemifacial spasm: comparison with oblique sagittal views of MRI.

A new technique, simultaneous display of magnetic resonance angiography (MRA) and multiplanar reconstruction (MPR), was performed by a workstation to identify the involved vessels in patients with trigeminal neuralgia (TN) or hemifacial spasm (HFS), and the results were compared with those of oblique sagittal MRI technique. Twelve patients with either HFS or TN were prospectively assessed by simultaneous display of MRA and MPR, and oblique sagittal techniques, to point out the neurovascular compression and to identify the involved vessels. Three-dimensional (3D) time-of-flight (TOF) spoiled gradient-echo (SPGR) images were acquired to create MRA and MPR. Oblique sagittal views were also created and displayed on films. A total of 15 vessels in 12 patients were identified as compressing vessels during surgery. Simultaneous display of MRA and MPR technique pointed out the presence of vessels at and/or around root entry/exit zone (REZ) in all 12 patients, but proper identification by the name of the individual vessel was correct in 13 of 15 cases. However, oblique sagittal technique indicated the presence of vessels at and/or around REZ in 11 patients, but only 8 of 14 vessels were correctly identified. Our new method, simultaneous display of MRA-MPR, facilitated correct identification of the involved vessels compared with the oblique sagittal view method.

Hemifacial Spasm↗

Crossline levels in serum and erythrocyte membrane proteins from patients with diabetic nephropathy.

Crossline is one of the structurally defined adducts of advanced glycation endproducts (AGEs) which has both a crosslink and fluorescence similar to AGE-protein in vivo. Crossline was measured in serum and erythrocyte membrane proteins (EMP) from 52 type 2 diabetic patients using a specific enzyme-linked immunosorbent assay system. Serum and EMP crossline levels in the diabetic patients were significantly higher than those in normal control. The patients with advanced diabetic nephropathy (serum creatinine levels of more than 1.2 mg/dl) had markedly elevated serum crossline levels compared to those with moderate diabetic nephropathy (clinical proteinuria) (180. 7+/-51.7 vs. 71.8+/-18.4 pmol/ml; P<0.01). On the other hand, there were no significant differences in EMP crossline levels between the two. EMP crossline levels in the patients with moderate diabetic nephropathy (8.8+/-2.9 pmol/mg protein) and those with advanced diabetic nephropathy (9.7+/-3.0 pmol/mg protein) were significantly higher than those without clinical proteinuria (6.4+/-1.9 pmol/mg protein; P<0.01). The present study demonstrated that EMP crossline levels were associated with the presence of nephropathy in patients with type 2 diabetes mellitus. Serum crossline levels were significantly influenced by remaining renal function. The measurement of crossline from a blood sample could provide us with important information for the study of clinical evaluation and pathogenesis of diabetic complications.

Aged↗