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Biomedical subjects

K Meguro

Publications and source records attributed to K Meguro.

At least 91 records · Page 5Linked to original sources

[Simultaneous rupture of multiple intracranial aneurysms: a case report].

A rare case of simultaneous rupture of multiple aneurysms is reported. A 68-year-old man presented severe headache and vomiting and was transferred to our hospital. CT scan showed subarachnoid hemorrhage (SAH) in the interhemispheric fissure, the right basal cistern, the right sylvian fissure and intracerebral hemorrhage (ICH) in the paraventricle area. Continuation of the hemorrhage could not be detected between SAH and ICH on CT scan. Multiple aneurysms were detected by angiograms on the anterior communicating artery (A-com) and the bifurcation and the distal portion of the left middle cerebral artery (MCA). These findings suggested that SAH was due to a ruptured aneurysm of A-com, and ICH was due to a ruptured aneurysm of the distal portion of MCA. Simultaneous rupture of multiple aneurysms was confirmed by surgical findings. This case indicates that the usual assumption of a single aneurysm rupture in a patient with multiple aneurysms may be erroneous.

Adult↗

[FLAIR images of cerebral and brain stem infarction].

FLAIR (fluid-attenuated inversion recovery) images are MR images obtained with an inversion recovery sequence having a long inversion time (TI) and a long echo time (TE). We examined 47 cases (56 graphics) of lacunar infarction (LI), 28 cases (32 graphics) of cortical infarction (CI) and 16 cases (23 graphics) of stem infarction (SI) with a FLAIR sequence having a repetitive time (TR) of 6500 msec, a TI of 1700 msec and a TE of 110 msec, and compared these graphics with T2-weighted images by spin-echo sequence (TR 2500 msec, TE 90 msec). LI and CI were better demonstrated with FLAIR images than with conventional T2-weighted images. FLAIR images were very useful in detecting lesions adjacent to the lateral ventricles and the cerebral sulci in particular, because the cerebrospinal fluid signals in the lateral ventricles and the cerebral sulci were low-intensity, with brain tissue appearing as high-intensity areas. In a number of old infarctions, FLAIR images revealed cystic structures, constructed out of internal low-intensity areas and peripheral high-intensity areas. These structural changes suggested that FLAIR images can provide information on pathological changes.

Aged↗

The role of the erythroid-specific delta-aminolevulinate synthase gene expression in erythroid heme synthesis.

Using antisense technology, the effects of suppressed gene expression of the erythroid-specific delta-aminolevulinate (ALA) synthase (ALAS-E) on heme synthesis, expression of mRNAs encoding an erythroid-specific transcription factor NF-E2, other heme pathway enzymes, and beta-globin were examined in murine erythroleukemia (MEL) cells. In MEL cells in which an antisense ALAS-E RNA was expressed (AS clone), sense ALAS-E mRNA levels in both untreated and dimethylsulfoxide (DMSO)-treated cells were decreased compared with their respective controls. Heme synthesis in AS clones was decreased in proportion to the suppressed levels of ALAS-E mRNA. In addition, mRNAs for ALA dehydratase, porphobilinogen deaminase, ferrochelatase (FeC), and beta-globin were also decreased in AS clones. There was a strong correlation between the level of ALAS-E mRNA and most of the mRNAs of the heme pathway enzymes and beta-globin. There was a decrease in the mRNA level of p45, but not of mafK, which are the large and the small subunits of NF-E2, respectively, in AS clones. Treatment of AS cells with hemin and ALA in the presence of DMSO partially restored the suppressed mRNA levels for beta-globin and FeC and heme content, respectively. These findings thus indicate that heme formation, which is determined by the level of ALAS-E, plays an essential role on gene expression of many proteins necessary for erythroid development.

5-Aminolevulinate Synthetase↗

Effects of thioperamide, a histamine H3 antagonist, on the step-through passive avoidance response and histidine decarboxylase activity in senescence-accelerated mice.

The effect of thioperamide, a histamine H3 receptor antagonist, on learning and memory was studied in the senescence-accelerated mice-prone strain (SAM-P/8) and normal-rate aging strain (SAM-R/1). In a passive avoidance test, SAM-P/8 mice of 12 months showed significant impairment of learning and memory compared with SAM-R/1 mice of the same age. Thioperamide significantly improved the response latency in SAM-P/8 mice when injected intraperitoneally at a dose of 15 mg/kg. The histidine decarboxylase (HDC) activity in the forebrain was significantly lower in SAM-P/8 mice than in SAM-R/1 mice. Thioperamide administration significantly potentiated HDC activity in the forebrain of SAM-P/8 mice as well as improving learning and memory. These results suggest that central histaminergic neurons may be involved in learning and memory impairment of SAM-P/8 mice, although other possibilities are not ruled out.

Aging↗

A novel translocation involving chromosomes 2, 9, 14, and 22 in chronic myeloid leukemia.

A 46-year-old man with chronic myelogenous leukemia was found to have a new complex translocation. In chronic phase, all of the bone marrow cells had a rearrangement of a t(2;9;14;22) (p21;q34;q32;q11). Southern blot analysis of leukocyte DNA revealed rearrangement of the breakpoint cluster region (bcr) within the 5.8-Kb bcr. The patient eventually died in blast crisis 28 months later. The cytogenetic findings of bone marrow cells showed a 46,XY,t(2;9;14;22)(p21;q34;q32;q11),add(1p),del(3q) karyotype in blast crisis.

Chromosome Banding↗

Principle of the bark of Phellodendron amurense to suppress the cellular immune response: effect of phellodendrine on cellular and humoral immune responses.

Previously we have isolated the quaternary base alkaloids, magnoflorine and phellodendrine, from Phellodendri Cortex (cortex of Phellodendron amurense Rupr., Rutaceae) as the biologically active principles to suppress local graft-versus-host (GvH) reactions in mice. In this paper, we focus on phellodendrine. Phellodendrine suppressed local semisyngeneic GvH reactions and systemic allogeneic GvH reactions in X-ray irradiated recipient mice. Phellodendrine also suppressed the induction phase of sheep red blood cell (SRBC)-induced delayed type hypersensitivity in mice and tuberculin-induced delayed type hypersensitivity in guinea pigs, but did not suppress the effector phase of these reactions. Surprisingly, phellodendrine, unlike prednisolone and cyclophosphamide, did not affect antibody production in mice to SRBC. Phellodendrine was expected to be a valuable new type of immunosuppressor against the cellular immune response.

Animals↗

Sleep disturbance in elderly patients with cognitive impairment, decreased daily activity and periventricular white matter lesions.

We investigated how sleep disturbance is correlated with brain lesions, cognitive impairment and decreased daily activity (ADL). Two hundred and four chronically ill patients including patients with vascular dementia were classified into eight groups based on cognitive function, ADL and grades of PVL (periventricular lucency) as shown by computerized tomography. Visual monitoring of the sleep/wake state was performed hourly for 14 consecutive days and the daytime sleep hours and the nighttime sleep hours were determined based on detected disturbances in the sleep/wake pattern. Whether any specific infarcted regions were correlated with sleep disturbance was also evaluated. We found that daytime sleep hours were increased and nighttime sleep hours were decreased by three single factors: cognitive impairment, decreased ADL and the severe grade of PVL. As for an interactive effect of the two factors, daytime sleep hours were increased by dementia with decreased ADL (independent of PVL) and increased by decreased ADL with the severe grade of PVL (independent of dementia). Although three factors affected sleep independently, ADL has an interactive effect on sleep with dementia and with PVL. No specific cortical regions related to sleep disturbance were found.

Activities of Daily Living↗

Multiple arteriovenous malformations of spinal cord and brain in a child.

A case of concurrent intracranial and spinal cord arteriovenous malformations (AVMs) is described. A 3-year-old girl presented with paraparesis, bladder-bowel disturbances and bilateral dysesthesia of the lower extremities due to a spinal hematoma, resulting from a spinal AVM. Magnetic resonance imaging revealed a hematoma and abnormal vessels in the spinal cord. The AVM was embolized with polyvinyl alcohol particles and silk sutures and was surgically removed. Later, this girl presented with disturbance of consciousness due to an intraventricular hemorrhage, resulting from a cerebral AVM. The cerebral AVM was surgically resected. The coexistence of bleeding cerebral and spinal AVMs is very rare.

Angiography, Digital Subtraction↗

Studies on antidiabetic agents. XII. Synthesis and activity of the metabolites of (+/-)-5(-)[p(-)[2-(5-ethyl-2-pyridyl)ethoxy]benzyl]-2,4- thiazolidinedione (pioglitazone).

The metabolites of (+/-)-5(-)[p(-)[2-(5-ethyl-2- pyridyl)ethoxy]benzyl]-2,4-thiazolidinedione (1, pioglitazone), which is a representative insulin-sensitizing agent, were synthesized to confirm their structures and for studies of their pharmacological properties. Of the metabolites identified, a compound hydroxylated at the 2-position of the ethoxy chain (3) and compounds oxygenated at the ethyl side chain attached to the pyridine ring (4, 5) were found to be active, although the potency was slightly lower than that of the parent compound.

Animals↗

Synthesis of 3-ureido derivatives of coumarin and 2-quinolone as potent acyl-CoA: cholesterol acyltransferase inhibitors.

Novel 3-ureido derivatives of 4-phenylcoumarin and 4-phenyl-2-quinolone were synthesized and evaluated for acyl-CoA: cholesterol acyltransferase (ACAT)-inhibitory activity. These derivatives inhibited rat intestinal ACAT with IC50 values at the 10(-8) to 10(-9) M level and were found to normalize plasma cholesterol levels in cholesterol-fed rats when administered as dietary admixtures.

Animals↗

Effect of lymphokine-activated killer cells with or without radiation therapy against malignant brain tumors.

The use of autologous lymphokine-activated killer (LAK) cells to treat malignant brain tumors was evaluated in 10 patients, one with metastatic malignant melanoma and nine with malignant glioma. LAK cells were obtained by culturing autologous peripheral blood lymphocytes with human recombinant interleukin-2 (rIL-2) for 7-28 days. All patients underwent surgery to remove as much tumor as possible and an Ommaya reservoir was implaced in the tumor cavity. Two of the 10 patients had received radiotherapy elsewhere, so were treated with LAK cells alone. Eight patients were treated with a combination of LAK cells and radiotherapy, using 1.8-2.0 Gy fractions given five times a week with a total dosage between 54 and 65 Gy. LAK cells and rIL-2 were injected to the tumor cavity via the Ommaya reservoir once a week for inpatients and once a month for outpatients. The duration of the LAK therapy ranged from 3 to 23 months (mean 13.7 mos). Neuroimaging evaluation revealed two complete responses, three partial responses, four no changes, and one progressive disease. In one patient with pontine glioma, the Karnofsky performance score was raised from 20 to 60. There were no side effects after the injection of LAK cells and rIL-2. The results suggest low-dose LAK therapy is a useful and safe treatment modality for malignant brain tumors.

Adult↗

Gait disturbance of patients with vascular and Alzheimer-type dementias.

The gaits of 15 patients with senile dementia of the Alzheimer type and 15 with vascular dementia were compared with those of 15 healthy control subjects. Patients with senile dementia showed significantly slower velocity and shorter step length than the healthy controls, and those with vascular dementia exhibited a reduction on these two variables relative to patients with senile dementia of the Alzheimer type.

Accidental Falls↗

[Low incidence of point mutation of N-ras oncogene in human gliomas].

We examined the incidence of point mutations in codon 12 and 61 of N-ras gene in human gliomas using PCR with mismatched primers. This method detects point mutations. PCR with mismatched primers induced restriction sites in normal DNA but not in mutational DNA. Genomic DNAs were extracted from paraffin-embedded tissues and were amplified with nested PCR. Among 17 cases, point mutation has not been able to be found so far, when examined in codon 12 of N-ras gene and among 10 cases in codon 61 of N-ras gene. It can thus be said that point mutational activation of N-ras oncogene is an uncommon event in human gliomas.

Base Sequence↗

[Response-oriented salvage chemotherapy with mitoxantrone, etoposide and enocitabine for previously treated acute myeloid leukemia. Tohoku Leukemia Study Group].

Twenty-two patients with previously treated acute myeloid leukemia (AML) received salvage chemotherapy with mitoxantrone, 5 mg/m2/d on days 1 to 3, etoposide, 70 mg/m2/d on days 1 to 5, and enocitabine, 170 mg/m2/d on days 1 to 7 (BHAC-ME). Additional mitoxantrone, etoposide (both for up to 2 days) and enocitabine (for up to 7 days) were given if the bone marrow obtained on day 8 was not severely hypoplastic. Mitoxantrone and etoposide had been previously administered in 14 and 15 patients, respectively. Seven patients had primary resistance; 14 patients had first relapse (4 early and 10 late): and 2 patients had second relapse. Overall, seven patients (31%) achieved a complete remission; 7/14 with first relapse, and 0/8 with primary resistance or second relapse. Four patients, 3 with primary resistance and 1 with first relapse, died of infectious complication in aplasia. First relapse patients who had been previously treated both with mitoxantrone and etoposide, had a lower CR rate than the other first relapse patients [2/8 (25%) vs 5/6 (86%)], although patient characteristics such as duration of first CR, initial karyotype, and performance status, were similar between the two groups. We conclude that response-oriented BHAC-ME regimen is still active in first relapse AML patients unless they have received both mitoxantrone and etoposide previously.

Acute Disease↗

Novel acyl-CoA:cholesterol acyltransferase inhibitors. Synthesis and biological activity of 3-quinolylurea derivatives.

A series of 3-quinolylurea derivatives (1) was synthesized and evaluated for acyl-CoA:cholesterol acyltransferase (ACAT) inhibitory activity. For in vitro studies, the most potent inhibitory activity was found in derivatives having substituents at the 6,7- or 6,8-positions and an ortho-substituted phenyl group at the 4-position of quinoline ring. The 2,4-difluorophenyl group appeared to be the optimum N'-substituent of the urea moiety. The IC50 values of compounds 52-54 and 59 were in the nanomolar order. Plasma cholesterol-lowering activity of compounds 50, 52, and 54 was observed at less than 1 mg/kg/day in cholesterol-fed rats. Compound 52 was also hypocholesterolemic in hamsters fed a diet without loading cholesterol.

Animals↗

Assessment of dopamine metabolism in brain of patients with dementia by means of 18F-fluorodopa and PET.

By means of positron emission tomography (PET) and 18F-fluorodopa (FDOPA), a study was initiated to analyze the cerebral dopamine (DA) metabolism of 32 subjects including those with AD/SDAT and vascular dementia (VD, multi-infarct type). A semiautomated irregular ROI drawing routine to identify the striatum was developed that interactively defined the PET threshold pixels referring to the count histograms and location of the corresponding pixels. A comparative study by five examiners showed significant improvement in the area size definition and count linearity particularly for low contrast objects. The graphical plot was employed to calculate the FDOPA influx rate (Ki) for the ROI data with cerebellar radioactivity as an input function. The striatal Ki value was found to be relatively stable and did not show signs of a significant age-related change. The vascular patients had smaller Ki to the striatum than the aged control. Although the mean Ki of AD/SDAT was almost compatible with that of age-matched normals, their Ki was more scattered with higher and lower Ki cases. The multiple regression analysis revealed that the Ki could be predicted by age and the mini-mental state (MMS) performance (r2 = 0.590, p < 0.01 for AD/SDAT, r2 = 0.401, and p < 0.05 for VD). MMS was found to be a more dominant factor than age. We conclude that dopamine metabolism became disturbed as dementia became progressively severe.

Aged↗

Nicotine improves cognitive disturbance in senescence-accelerated mice.

Senescence-accelerated mice (SAM), a murine model of age-related deterioration in learning ability, were studied as to the acetylcholine (ACh) contents in the brain tissues and the effect of nicotine administration. We found that the ACh content of SAM-P/8 (accelerated senescence-prone) mice was lower than that of SAM-R/1 (accelerated senescence-resistant) mice in the midbrain thalamus and the hypothalamus. In addition, an IP administration of nicotine was found to improve learning ability of SAM-P/8 as shown by performance of a passive avoidance task. Nicotine may potentiate cognitive function in SAM-P/8.

Acetylcholine↗