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Biomedical subjects

K Meguro

Publications and source records attributed to K Meguro.

At least 109 records · Page 6Linked to original sources
PubMed1994

Molecular defects of uroporphyrinogen decarboxylase in a patient with mild hepatoerythropoietic porphyria.

The molecular defect of uroporphyrinogen decarboxylase (UROD) was examined in a patient with mild hepatoerythropoietic porphyria. To elucidate the UROD defect, we cloned UROD cDNAs from EBV-transformed lymphoblastoid cells of the proband using reverse transcriptase-polymerase chain reaction. Nucleotide sequence analysis of the cloned UROD cDNAs revealed two separate missense mutations, each occurring in a separate allele. One mutation was a Val134-->Gln transition, and was due to three sequential point mutations (T417G418T419-->CCA); the other mutation was a His220-->Pro transition (A677-->C). UROD phenotype studies demonstrated that the TGT-->CCA mutation was inherited from the father, and the A-->C mutation was inherited from the mother. In contrast to the null activity previously described for a mutant UROD from a patient with familial porphyria cutanea tarda, these mutant URODs had subnormal but substantial enzyme activities, when expressed in Chinese hamster ovary cells. This is the first demonstration of a mutation caused by three sequential base substitutions.

Adult↗
PubMed1994

[A clinicopathological study of senile dementia of Alzheimer's type (SDAT) and white matter lesions of Binswanger's type].

A clinicopathological study of senile dementia of Alzheimer's type (SDAT) accompanied by the white matter lesions of Binswanger's type was carried out. Fifty-seven patients, who were diagnosed as suffering from SDAT based on clinical and pathological criteria, were classified into two groups based on the white matter lesions of Binswanger's type. Namely, group 1 consisted of the SDAT patients without any subcortical or white matter lesions (30 cases); group 2 consisted of those with white matter lesions of Binswanger's type (11 cases). The other 9 cases included those with vascular lesions and 4 with some of the same pathological changes found in Parkinson's disease. Clinically, group 2 patients showed subcortical symptoms such as urinary incontinence, Parkinsonian gait, being accompanied by hypertension and arrhythmias. Periventricular lucency (CT) were common in group 2. Macroscopically, both groups showed moderately to severe atrophy, and the width of the corpus callosum of group 2 was narrower than that of group 1. There was no difference in cerebral arteriosclerosis between the groups. In microscopic findings, patients in group 2 showed diffuse distribution of cortical changes such as senile plaques as well as Alzheimer's senile plaques as well as Alzheimer's neurofibrillary tangles while those in group 1 showed various types of diffuse or local distribution. Arteriolosclerosis of the white matter were found in both groups. There was no difference in aortic atherosclerosis and/or heart disease. The complication of white matter lesions of Binswanger's type was not a rare finding in SDAT.

Aged↗
PubMed1994

[Surgical indication for unruptured cerebral aneurysm in patients with ischemic cerebrovascular disease].

A series of 44 cases is presented of patients who received surgical treatment for unruptured aneurysms in the anterior circulation, and which were associated with ischemic cerebrovascular disease (CVD). The age of patients varied from 34 to 76 (mean 62.8) years old. The associated ischemic CVD was transient ischemic attack (TIA) in ten, minor completed stroke in 23, and major completed stroke in 11 cases. Thirty five patients recovered fully. However, there were three deaths due to new cerebral infarction or delayed intracranial hemorrhage within 30 days after surgery (mortality 6.8%). Transient morbidity occurred in four patients (9.1%), and permanent morbidity in two patients (4.5%). In six cases, new ischemic events occurred after the surgery. In contrast, all 40 patients whose unruptured aneurysms were not associated with CVD fully recovered from the surgery they underwent. The authors indicate three risk factors which might lead to complication; diabetes mellitus, aneurysms located in the middle cerebral artery, and those larger than 6mm in diameter. Another three life-threatening factors are; elderly patients (> 65 year-old), male, aneurysms larger than 7mm in diameter. Direct surgery for unruptured aneurysms in ischemic CVD patients should be considered in cases free of risk factors indicated above. Eight cases in this series had extracranial carotid artery stenosis on the same side as the aneurysm. Carotid endoarterectomy (CEA) was performed prior to aneurysmal clipping in six patients, and their postoperative courses were excellent. In two patients, clipping was performed prior to CEA, and transient morbidity occurred in one of them.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Sevoflurane MAC in the elderly].

Twenty four elderly surgical patients (mean age, 82 years) undergoing surgery were anesthetized with sevoflurane and oxygen. In these patients, the minimum alveolar concentration (MAC) for sevoflurane was determined. The MAC of sevoflurane in the elderly was 1.22 +/- 0.09% (SE), and this value was found to be about 30% smaller than that of 40-50 year-old patients.

Adult↗
PubMed1993

Periventricular hyperintensity on magnetic resonance imaging correlated with brain ageing and atrophy.

Fifty-two patients with cerebrovascular risk factors without neurological abnormalities were reviewed with respect to periventricular hyperintensity (PVH) on T2-weighted magnetic resonance imaging (MRI); brain atrophy was also assessed by CT and T1-weighted MRI. Extensive PVH showed a stronger correlation with age-related atrophy than mild or absent PVH. The relative volume of brain affected by PVH, calculated by computer, also correlated with brain atrophy, especially ventricular enlargement. The effects of PVH on brain ageing and atrophy is discussed.

Aged↗
PubMed1993

Functional analysis of cDNAs for two types of human heme oxygenase and evidence for their separate regulation.

We cloned a cDNA coding for a putative human heme oxygenase isozyme, designated type 2 (HO-2), and analyzed its function by transient expression assays. HeLa cells transfected with either HO-2 cDNAs or a cDNA coding for authentic heme oxygenase (HO-1) expressed the activity of heme oxygenase, although no activity was detected in the mock transfected cells. Using specific anti-HO-1 antibody, we showed that expression of a HO-1 cDNA resulted in the increase in its protein levels, but HO-1 protein was not detectable in the cells expressing HO-2 cDNAs. We thus confirmed the functional identity of HO-1 and HO-2. Then, we analyzed their expression in an erythroid cell line, YN-1-0-A. Treatment with hemin or by heat shock (42 degrees C) led to a remarkable increase in the HO-1 mRNA levels, while HO-2 mRNA expression was not induced at all, suggesting that they are under separate regulation.

Cell Line↗
PubMed1993

Two chronic myelogenous leukaemia cell lines which represent different stages of erythroid differentiation.

We established two cell lines, YN-1 and Y-1K, from the peripheral blood of two chronic myelogenous leukaemia patients in blastic crisis. Characterization of the YN-1 and Y-1K cells revealed that these cells expressed erythroid lineage markers. However, there was a marked difference in the level of gamma-globin mRNA and haemoglobin in YN-1 and Y-1K cells. YN-1 contained approximately 1-5% benzidine-positive staining cells, whereas no benzidine-positive cells were observed in Y-1K cells. Haemoglobin production in YN-1 cells was markedly increased with various chemical inducers of erythroid differentiation, but was not in Y-1K cells. In contrast, Y-1K cells expressed CD34 stem cell antigen and CD41 megakaryocyte-specific antigen. These observations suggested that, although both cell lines were committed to the erythroid lineage, each cell line represented a distinct differentiation stage in the erythroid differentiation programme. Y-1K seemed to correspond to an early stage of cells in erythroid lineage, whereas YN-1 represented a more advanced stage in human erythropoiesis.

Adult↗
PubMed1993

Acute subdural hematoma--prediction of outcome with a linear discriminant function.

We devised a linear discriminant function to predict the outcome for patients with acute subdural hematoma (ASDH) based on a consecutive series of 170 ASDH cases with mild to severe head injury [Glasgow Coma Scale (GCS) 3-15]. Functional recovery was achieved in 50.0% of patients and the mortality was 36.5%. The relationship between initial clinical and radiological signs and the outcome 3 months after admission was studied retrospectively by Mann-Whitney's U-test and Pearson's chi-squared test. Fourteen factors (GCS, pupillary response, motor paresis, age, hematoma volume and thickness, midline shift, association with cerebral contusion and subarachnoid hemorrhage, obliteration of the basal, ambient, or quadrigeminal cistern on computed tomography, fibrin-fibrinogen degradation product level, and intracranial pressure) were found to correlate significantly (p < 0.01) with outcome. Linear discriminant functions were formulated by multivariate analysis to investigate the relationship between these factors and recovery or poor prognosis. The following formula was obtained: Z = -0.110 + 0.013 (Age) - 0.108 (GCS) + 0.397 (Eye) + 0.003 (Shift) + 0.268 (Ambient). Functional recovery could be predicted by a negative Z value, with an accuracy of 90.59%. This simple discriminant function is useful for predicting the outcome of ASDH.

Adult↗
PubMed1993

Effect of nicotine on cognitive disturbance in animals with acetylcholine deficient brain.

The effect of nicotine on learning disturbance was tested in rats fed with a choline-deficient diet (Ch free) or in senescence-accelerated mice (SAM). Concentration of acetylcholine in the brain was significantly lower in rats fed with Ch free and SAM. Passive avoidance learning shows that rats fed with Ch free and SAM showed significantly impaired learning, compared to controls. Nicotine (0.04 mg/kg) administered intraperitonealy significantly improved learning in animals with learning disturbances, as well as in controls. Vitamin B12 facilitated acetylcholine synthesis or release in the brain and improved the cognitive disturbance. We therefore suggest that acetylcholine contributes to learning and that nicotine may improve learning in an acetylcholine deprived rats.

Acetylcholine↗
PubMed1993

[Effects of different concentrations of an inhaled anesthetic agent, sevoflurane on sympatho-adrenal medullary functions in rats].

Effects of different inspiratory concentrations of an inhaled anesthetic agent, sevoflurane on efferent activities of the adrenal sympathetic nerve and adrenal catecholamine secretion were examined using rats either under the resting condition or during noxious mechanical stimulation of a hindpaw. Under the resting condition, an increase in the inspiratory concentration of sevoflurane from 2.1% to 4.2% caused a gradual decrease in the adrenal nerve activity and the catecholamine secretion. When noxious mechanical stimulation was applied to a hindpaw by pinching, both the adrenal nerve activity and adrenaline secretion increased, and the responses were attenuated dose-dependently by sevoflurane concentration of between 2.1% and 4.2%. Noradrenaline secretion was unchanged during the pinching stimulation throughout the administration of sevoflurane 2.1-4. 2%.

Adrenal Medulla↗
PubMed1993

[MR imaging of associated brain injuries in cases with acute extradural hematoma].

To assess the efficacy of magnetic resonance (MR) imaging for detection of associated brain injuries in cases with extradural hematoma (EDH), 32 patients of EDH were examined by MR. CT detected associated lesion in eleven patients (34%), while MR detected them in 24 patients (75%). MR is more sensitive than CT in detecting associated lesions, especially when T2 weighted imaging is used. Non-hemorrhagic contusions adjacent to EDH, and near the cranial base were well shown by MR, however they tended to be missed by CT. EEG findings were clearly related to abnormalities detected by MR. Coupling between functional change and organic change was confirmed. The improved detection and anatomic localization of associated brain injuries by MR should allow more accurate assessment of brain injuries, and sophisticated management of EDH patient. The authors also discussed on the cardiorespiratory monitoring and support during MRI examination in critically ill patients.

Adolescent↗
PubMed1992

Studies on antidiabetic agents. 11. Novel thiazolidinedione derivatives as potent hypoglycemic and hypolipidemic agents.

In the course of further chemical modification of the novel antidiabetic pioglitazone (AD-4833, U-72,107), a series of 5-[4-(2- or 4-azolylalkoxy)benzyl- or -benzylidene]-2,4-thiazolidinediones was prepared and evaluated for hypoglycemic and hypolipidemic activities in insulin-resistant, genetically obese, and diabetic KKA(y) mice. Replacement of the 2-pyridyl moiety of pioglitazone by a 2- or 4-oxazolyl or a 2- or 4-thiazolyl moiety greatly enhanced in vivo potency. The corresponding 5-benzylidene-type compounds, in which a methine was used as a linker between the benzene ring and the thiazolidinedione ring, also had potent biological activity. Among the compounds synthesized, 5-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]-2,4- thiazolidinedione (18) exhibited the most potent activity, more than 100 times that of pioglitazone. The synthesis and structure-activity relationships for this novel series of derivatives are detailed.

Animals↗
PubMed1992

The effects of morphine administered into the vertebral artery on the somatosympathetic A- and C-reflexes in anesthetized cats.

The effects of morphine (0.2-200 micrograms/kg) administered into the brain stem via a vertebral artery on the somatosympathetic A- and C-reflexes evoked in a cardiac sympathetic nerve by electrical stimulation of somatic myelinated (A) and unmyelinated (C) afferent nerve fibers in anesthetized cats were examined. The intravertebral arterial administration of 20-200 micrograms/kg morphine depressed dose-dependently both the somatosympathetic A- and C-reflexes. Following the administration of 200 micrograms/kg morphine, the amplitudes of the sympathetic A- and C-reflexes were depressed to 71 +/- 8% and 80 +/- 8% of the control magnitude, respectively. Injection of 2-200 micrograms/kg morphine caused hypotension in a dose-dependent manner. It is concluded that morphine administered in the brain stem via the vertebral artery produced a nonselective and slight depression of both the somatosympathetic A- and C-reflexes by acting at the level of brain stem.

Anesthesia↗
PubMed1992

Histamine H1 receptors in human brain visualized in vivo by [11C]doxepin and positron emission tomography.

Histamine H1 receptors in the living human brain were visualized by positron emission tomography (PET) using [N-11C-methyl]-(E)-doxepin ([11C]doxepin). The regional distribution of the carbon-11-labeled compound in the brain corresponded well with that of the histamine H1 receptors measured in vitro using [3H]pyrilamine. The radioactivity in the brain was significantly reduced by intravenous pretreatment with d-chlorpheniramine (5 mg), a histamine H1 antagonist. The regional distribution of [11C]doxepin in the brain 45-90 min after its injection was almost the same as that of [11C]pyrilamine in the brain. These results indicate that [11C]doxepin is useful for measuring histamine H1 receptors in human brain by PET.

Adult↗
PubMed1992

Vitamin B12 improves cognitive disturbance in rodents fed a choline-deficient diet.

The effect of vitamin B12 on learning disturbance was tested in rats. Rats were fed a choline-enriched, choline-deficient, and choline-deficient diet with vitamin B12. Concentrations of acetylcholine in the brain were significantly lower in rats fed a choline-deficient diet than rats fed a choline-enriched diet. Passive avoidance learning shows that rats on a choline-deficient diet showed significantly impaired learning compared to rats on a choline-enriched diet. However, there was no significant difference of acetylcholine in the brain or in the passive avoidance learning between rats fed a choline-enriched and a choline-deficient with vitamin B12 diet. We, therefore, suggest that vitamin B12 potentiates learning in an acetylcholine-deprived brain.

Acetylcholine↗