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Biomedical subjects

M Fukui

Publications and source records attributed to M Fukui.

At least 199 records · Page 11Linked to original sources
PubMed1998

Molecular specificity of a medium chain acyl-CoA synthetase for substrates and inhibitors: conformational analysis.

Amino acid conjugation is an important route of detoxification of xenobiotic and endogenous carboxylic acids. The specificity of the purified medium chain acyl-CoA synthetase catalyzing the first reaction of amino acid conjugation was investigated further for substrates and inhibitors. Molecular modeling techniques were applied to derive the molecular characteristics of substrates and inhibitors for the medium chain acyl-CoA synthetase. The purified enzyme accepted not only straight medium chain fatty acids but also aromatic acids. Of the arylacetic acids, activity was obtained with naphthylacetic acids, whereas introduction of a methyl group at the alpha-position caused loss of activity. High activity was also observed with cyclohexanoic acid. Diflunisal, 2-hydroxydodecanoic acid, and nalidixic acid inhibited the medium chain acyl-CoA synthetase activity for hexanoic acid, with Ki values of 0.8, 4.4, and 12.3 microM, respectively. The inhibitory carboxylic acids were competitive with respect to hexanoic acid. The hydroxyl or ketone (oxo) groups at the beta-position of carboxylic acids were an important determinant for inhibitory activity. All substrates and inhibitors contained a flat hydrophobic region coplanar to the carboxylate group. In addition, the substrates had negative values for charge on the carbon in the beta-position of carboxylic acids.

Acetates↗
PubMed1998

Stroke due to a fusiform aneurysm of the cervical vertebral artery: case report.

Aneurysms of the cervical vertebral artery (VA) are uncommon; they are often caused by trauma or spontaneous dissection. A fusiform aneurysm without evidence of atherosclerosis or dissection has not been reported previously. A 46-year-old man presented with a pontine infarct. Imaging revealed a fusiform aneurysm of the left VA at the C5-6 level, with occlusion of the basilar artery. Associated minor anomalies included fusion of the vertebral bodies of C5 and C6, cervical rib and platybasia. The left VA arose directly from the aortic arch and entered the transverse foramen at the C4 level. Hyperextension and left lateral flexion of the neck caused kinking of the VA proximal to the aneurysm. Turbulent flow in the aneurysm lumen was noted on angiography.

Cerebral Angiography↗
PubMed1998

Delayed cerebral radionecrosis with a high uptake of 11C-methionine on positron emission tomography and 201Tl-chloride on single-photon emission computed tomography.

A 47-year-old woman, who 2.5 years previously had undergone resection of a malignant astrocytoma of the left temporal lobe followed by radiotherapy, was found to have a mass in the left frontal lobe. This showed high uptake of thallium-201 (201Tl) on single-photon emission computed tomography and 11C-methionine on positron-emission tomography, suggesting recurrent tumour. Histological examination of the resected lesion, however, revealed it to be radionecrosis. This case thus illustrates a diagnostic pitfall in the use of these investigations for distinguishing radionecrosis from recurrent malignant glioma.

Adult↗
PubMed1998

A comparative study of thallium-201 SPET, carbon-11 methionine PET and fluorine-18 fluorodeoxyglucose PET for the differentiation of astrocytic tumours.

Thallium-201, carbon-11 methionine (MET) and fluorine-18 fluorodeoxyglucose (FDG) have all been used to assess brain tumours. The aim of this study was to determine which of these tracers are of use for evaluating the histological grade and the extent of astrocytoma. 201Tl single-photon emission tomography (SPET), MET positron emission tomography (PET) and FDG PET were all performed in 23 patients (13 men, 10 women) with newly diagnosed astrocytic tumours [seven with astrocytoma (grade II), ten with anaplastic astrocytoma (grade III) and six with glioblastoma (grade IV)]. The 201Tl uptake of the tumours was evaluated by a lesion-to-normal region count ratio. Both MET and FDG uptake of the tumours was evaluated by a semiquantitative analysis using the standardized uptake value. 201Tl uptake was found to increase in rank order with histological grade and was significantly different among the three groups (grade II: 1.51+/-0.36; grade III: 2.58+/-1.50; grade IV: 7. 65+/-3.84). MET uptake in grade II (1.49+/-0.44) was also significantly lower than that in both grade III (3.29+/-1.44) and grade IV (3.20+/-0.92). FDG uptake was not significantly different among the three groups (grade II: 2.90+/-0.45; grade III: 3.86+/-1. 56; grade IV: 3.57+/-0.83). No significant correlation was observed between 201Tl uptake and either MET uptake or FDG uptake. In most patients, the extent of the increased MET uptake was the largest while that of the increased FDG uptake was the smallest. In patients with positive 201Tl uptake, the extent of the 201Tl uptake was equal to or smaller than that of gadolinium enhancement. For evaluation of histological grade of astrocytic tumours. 201Tl is therefore considered to be useful though the 201Tl uptake in some grade III astrocytomas was not different from that in grade II astrocytomas. MET was found to be highly useful for detecting astrocytomas, for differentiating between benign and malignant astrocytomas, and for evaluating the extent of astrocytomas; however, it was not sufficiently useful permit evaluation of the histological grade. FDG was not found to be useful either for evaluating the histological grade or for differentiating between benign and malignant astrocytomas.

Astrocytoma↗
PubMed1998

Supratentorial primitive neuroectodermal tumours: a report of four cases with an unusual clinical course in one patient.

Four children, who were treated for supratentorial primitive neuro-ectodermal tumours between 1986 and 1995 at Kyushu University Hospital, are here presented. The initial characteristic symptoms and signs of these patients included vomiting and headache, followed by motor weakness. All patients underwent direct surgery for their tumours while 2 also received a course of postoperative radio-therapy. After these treatments, 3 died within 4 months after diagnosis, whereas one infant, who underwent a total removal of the tumour but had no adjuvant therapy, is still alive after a follow-up period of 4 years. Most of the tumour cells of these 4 cases were poorly differentiated neuro-ectodermal cells, but some also showed variable differentiation along the glial and/or neuronal lines. While such differentiation had no impact on the clinical course of the patients, the malignant potential as assessed by the percentage of MIB1-positive cells showed a good correlation with the clinical features; the 3 cases with a rapid clinical course had MIB1 staining indices of more than 2%, and one case, who survived more than 4 years, had the same indices of 0.2% as found in benign tumours. Although "PNETs" of Hart and Earl share certain clinical features, they may be a group of tumours heterogeneous in their origins, histogenesis, and biological behaviours.

Biomarkers, Tumor↗
PubMed1998

Radiation-induced brain tumours: potential late complications of radiation therapy for brain tumours.

The development of neoplasms subsequent to therapeutic cranial irradiation is a rare but serious and potentially fatal complication. In this study, we retrospectively reviewed the clinical and pathological aspects of 11 patients who underwent cranial irradiation (range, 24-110 cGy) to treat their primary disease and thereafter developed secondary tumours within a span of 13 years. All tumours arose within the previous radiation fields, and satisfied the widely used criteria for the definition of radiation-induced neoplasms. There was no sex predominance (M: 5, F: 6) and the patients tended to be young at irradiation (1.3-42 years; median age: 22 years). The median latency period before the detection of the secondary tumour was 14.5 years (range: 6.5-24 years). Meningiomas developed in 5 patients, sarcomas in 4, and malignant gliomas in 2. A pre-operative diagnosis of a secondary tumour was correctly obtained in 10 patients based on the neuro-imaging as well as nuclear medicine findings. All patients underwent a surgical removal of the secondary tumour, 3 underwent additional chemotherapy, and one received stereotactic secondary irradiation therapy. During a median of 2 years of follow-up review after the diagnosis of a secondary tumour, 3 patients died related to the secondary tumours (2 sarcomas, 1 glioblastoma), one died of a recurrent primary glioma, while the remaining 7 have been alive for from 10 months to 12 years after being treated for the secondary tumours (median: 3 years). Based on these data, the clinicopathological characteristics and possible role of treatment for secondary tumours are briefly discussed.

Adolescent↗
PubMed1998

Three-dimensional localization of subclinical ictal activity by magnetoencephalography: correlation with invasive monitoring.

BACKGROUND: Although magnetoencephalography (MEG) provides accurate information on the spatial distribution and temporal patterns of the "interictal" epileptic activities, it is interictal in nature and therefore also prone to all the problems associated with interictal data. METHODS: We investigated the subclinical "ictal" epileptic activity with a 37-channel, large-array biomagnetometer and mapped the data onto a three-dimensional image in a patient with intractable frontal lobe epilepsy. Dipole source localization was calculated based on magnetic fields for both the interictal and subclinical ictal activities. RESULTS: The current dipoles of the interictal MEG spikes (MEG irritative zone) were revealed to be scattered in the left anterior frontal lobe, whereas that of the subclinical ictal onset (MEG subclinical ictal onset zone) was surrounded by the interictal dipole cluster. The dipole source localization of the propagating activities was not calculated with a single dipole model. The MEG subclinical ictal onset zone correlated well with the ictal onset zone subsequently recorded by invasive subdural electrophysiological monitoring. After multiple subpial transection of the deduced epileptogenic area, a dramatic reduction of the seizures occurred. CONCLUSION: These results illustrate the potential of MEG for localizing the epileptogenic foci with high spatial and temporal resolution.

Adolescent↗
PubMed1998

Nasal absorption kinetic behavior of azetirelin and its enhancement by acylcarnitines in rats.

PURPOSE: The long-term stability and nasal absorption characteristics of a basic nasal formulation of azetirelin, a thyrotropin-releasing hormone analog and its absorption enhancement by incorporation of acylcarnitines in the formulation were investigated. METHODS: The long-term stability of basic nasal azetirelin formulations at 25 degrees C was predicted by calculation from the Arrhenius plot of the data on 6 months' storage at 40, 50 and 60 degrees C. Nasal azetirelin absorption characteristics were kinetically examined by intranasal administration to rats, determination of plasma azetirelin level by radioimmunoassay, and fitting the data to a two-compartment model including absorption rate. RESULTS: Basic nasal azetirelin formulations of pH 4.0 and pH 5.1 were predicted to be highly stable. Residual azetirelin after 2 years storage at 25 degrees C was greater than 95%. Nasal absorption characteristics of this formulation in the pH 4.0-6.3 range showed pH-dependency, with pH 4.0 showing the highest absolute bioavailability (Bioav) of 17.1%. This nasal Bioav was 21 times greater than that of oral administration (0.8%). Acylcarnitines with 12 or more carbon atoms in the acyl chain greatly enhanced nasal absorption of azetirelin: Bioavs with lauroylcarnitine chloride (LCC) and palmitoylcarnitine chloride were 96.9% and 72.9%, respectively. This enhancement by LCC plateaued at the low concentration of 0.1%. CONCLUSIONS: The basic nasal azetirelin formulation at pH 4.0 is stable and shows adequate absorption, with nasal absorption having greater Bioav than oral absorption. The 12-carbon acylate LCC was the strongest enhancer among acylcarnitines and provided near-total delivery of the administered dose to the blood.

Absorption↗
PubMed1998

HLA-DRB1 alleles contribute to determining the prognosis of Japanese diabetes mellitus positive for antibodies to glutamate decarboxylase.

Diabetes mellitus positive for antibodies to glutamate decarboxylase is heterogeneous as far as the degree of impairment of endogenous insulin release, though antibodies to glutamate decarboxylase are the most useful marker for future insulin deficiency. To investigate what determines the prognosis of diabetes mellitus positive for antibodies to glutamate decarboxylase, we measured HLA-DRB1 alleles in three groups: 77 cases of insulin-dependent diabetes mellitus (IDDM), 44 of non-insulin-dependent diabetes mellitus (NIDDM) with secondary failure of oral hypoglycemic therapy, and 22 of NIDDM well controlled by diet and/or sulfonylurea agents. The proportion of susceptible and resistant alleles to IDDM determined the degree of insulin deficiency, and comparison of IDDM to NIDDM well controlled by diet and/or sulfonylurea agents revealed significant differences in DRB1*0405 (P < 0.05; RR = 2.82 and RR = 0.89, respectively) and DRB1*1502 (P < 0.001; RR = 0.02 and RR = 2.19, respectively). This study revealed that HLA-DRB1 alleles contribute to determining the prognosis of Japanese diabetes mellitus positive for antibodies to glutamate decarboxylase.

Adolescent↗
PubMed1998

Microsurgical anatomy for lateral approaches to the foramen magnum with special reference to transcondylar fossa (supracondylar transjugular tubercle) approach.

Microsurgical anatomy for lateral approaches to the foramen magnum, especially for transcondylar fossa (supracondylar transjugular tubercle) approach, was studied using cadavers. The transcondylar fossa approach is an approach in which extradural removal of the posterior portion of the jugular tubercle through the condylar fossa is added to the far lateral approach. Some differences between this approach and the transcondylar approach are demonstrated. The atlanto-occipital joint and the jugular tubercle are obstacles for the lateral approaches. The condylar fossa forming the external occipital surface of the jugular tubercle is located supero-posterior to the occipital condyle. The fossa is limited laterally by the sigmoid sulcus and the jugular foramen. The posterior condylar canal communicating anteriorly with the distal end of the sigmoid sulcus, the jugular foramen, or the hypoglossal canal opens at the bottom of the fossa. The condyle is situated inferior to the posterior condylar and hypoglossal canals, and the jugular tubercle is located superior to them. In the transcondylar fossa approach the posterior part of the jugular tubercle is extradurally removed, but the condyle and the atlanto-occipital joint are untouched. On the other band, in the transcondylar approach the medial parts of the condyle and the lateral mass of Cl are removed. The latter approach offers better visualization of the inferior part of the foramen magnum. The essential difference of the two approaches is in the direction of looking and the extent of resection of the atlanto-occipital joint. Both approaches offer excellent view of the ventral dural space in the lower clivus and the foramen magnum, but the level of exposure differs somewhat between them. In the lateral approaches to the foramen magnum, the condylar fossa, the posterior condylar canal, and the posterior condylar emissary vein all play an important role as intraoperative anatomical landmarks.

Journal Article↗
PubMed1998

Expression of inducible nitric oxide synthase in rats following subarachnoid hemorrhage.

The possible expression of the inducible isoform of nitric oxide synthase (iNOS) was examined in a rat model of subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage was induced by the injection of autologous blood into the cisterna magna using stereotactic technique under general anesthesia. The rats were then killed at specific time intervals between 4 hours to 7 days after SAH. Reverse-transcriptional polymerase chain reaction (RT-PCR) revealed the expression of iNOS mRNA in the homogenate obtained from the tissue around the circle of Willis one day after SAH (Day 1). No iNOS mRNA was detected either in the sham-operated animals, or at any of the other time intervals after SAH. An immunohistochemical study was performed to examine the localization of iNOS-positive cells in the central nervous system. Inducible NOS immunoreactivity was thus observed in the mononuclear cells and polymorphonuclear cells infiltrating into the subarachnoid space of the basal cistern on Day 1. This immunoreactivity persisted faintly on Day 2, but had completely disappeared on Day 7. A vascular diameter study disclosed a vasoconstrictive change in the middle cerebral artery after SAH. Taken together, these results are thus considered to confirm the expression of iNOS in the infiltrated inflammatory cells after the insult of SAH, which may therefore play an introductory role in the development of the pathological series of events after SAH, including vasospasm.

Animals↗
PubMed1998

Magnetic source imaging of the sensory cortex on the surface anatomy MR scanning.

Surgery for lesions either within or close to the central sulcus of the brain always carries the risk of inducing iatrogenic motor or sensory deficits. We performed advanced magnetic source imaging (MSI) of the somatosensory cortex combined with 3-dimensional (3-D) surface anatomy scanning (SAS) of magnetic resonance imaging on 9 patients who had peri-Rolandic lesions, including 7 tumor cases, 1 arteriovenous malformation and 1 focal cortical dysplasia. 3-D MSI mapped out the entire somatosensory homunculus and localized the lesion on a cortical surface image. The results were then used for developing an appropriate surgical strategy and also as a reference in the operating room. This relationship and deduced localization were both confirmed by a cortical recording of the somatosensory evoked potentials at the time of surgery. Case histories of selected patients are briefly reported to demonstrate how the method can be used to improve the safety of surgical excisions of peri-Rolandic lesions. MSI on SAS including the cortical veins, was thus found to provide a readily interpretable presurgical road map of the cortical surface which compares favorably to that of intraoperative brain mapping.

Adolescent↗
PubMed1998

Sulfate-reducing bacteria and their activities in cyanobacterial mats of solar lake (Sinai, Egypt).

The sulfate-reducing bacteria within the surface layer of the hypersaline cyanobacterial mat of Solar Lake (Sinai, Egypt) were investigated with combined microbiological, molecular, and biogeochemical approaches. The diurnally oxic surface layer contained between 10(6) and 10(7) cultivable sulfate-reducing bacteria ml-1 and showed sulfate reduction rates between 1,000 and 2, 200 nmol ml-1 day-1, both in the same range as and sometimes higher than those in anaerobic deeper mat layers. In the oxic surface layer and in the mat layers below, filamentous sulfate-reducing Desulfonema bacteria were found in variable densities of 10(4) to 10(6) cells ml-1. A Desulfonema-related, diurnally migrating bacterium was detected with PCR and denaturing gradient gel electrophoresis within and below the oxic surface layer. Facultative aerobic respiration, filamentous morphology, motility, diurnal migration, and aggregate formation were the most conspicuous adaptations of Solar Lake sulfate-reducing bacteria to the mat matrix and to diurnal oxygen stress. A comparison of sulfate reduction rates within the mat and previously published photosynthesis rates showed that CO2 from sulfate reduction in the upper 5 mm accounted for 7 to 8% of the total photosynthetic CO2 demand of the mat.

Bacteria↗
PubMed1998

Dissociated expression of collagen type IV subchains in diabetic kidneys of KKAy mice.

Diabetic nephropathy is characterized by thickening of the glomerular basement membrane and expansion of the mesangial matrix. The glomerular basement membrane is assembled from at least five genetically distinct collagen IV chains. In patients with diabetic nephropathy, differential distribution of these components has been demonstrated. In order to clarify the relationship between progression of diabetic nephropathy and altered type IV collagen assembly in the renal cortex, we examined steady state mRNA levels encoding collagen IV subchains in the kidney cortices of spontaneously diabetic KKAy mice and nondiabetic C57black mice as controls. They were sacrificed at 4, 8, 16, and 24 weeks of age. Northern and dot blot analyses were performed using 32P-labeled mouse probes for classical alpha1(IV) and alpha2(IV) and for alpha3(IV), alpha4(IV), and alpha5(IV) minor chains. The mRNA levels for all collagen IV chains peaked at 4 weeks of age and declined rapidly thereafter in the nondiabetic mice. At all times, alpha1(IV) and alpha2(IV) mRNA expressions were abundant and almost unchanged in KKAy mice. In contrast, mRNA levels for alpha3(IV), alpha4(IV), and alpha5(IV) progressively changed with age. It appears that the expression of minor collagen IV chains is dissociated from the alpha1(IV) and alpha2(IV) chains in diabetic nephropathy. Moreover, an unbalanced increase in the production may affect collagen IV assembly and contribute to basement membrane thickening in diabetic nephropathy of KKAy mice.

Animals↗
PubMed1998

Genes that cause aberrant cell morphology by overexpression in fission yeast: a role of a small GTP-binding protein Rho2 in cell morphogenesis.

To identify the genes involved in cell morphogenesis in Schizosaccharomyces pombe, we screened for the genes that cause aberrant cell morphology by overexpression. The isolated genes were classified on the basis of morphology conferred. One of the genes causing a rounded morphology was identified as the rho2+ gene encoding a small GTP-binding protein. The overexpression of rho2+ resulted in a randomized distribution of cortical F-actin and formation of a thick cell wall. Analyses using cdc mutants suggested that the overexpression of rho2+ prevents the establishment of growth polarity in G1. The rho2+ gene was not essential, but among cells deleted for rho2+, those with an irregular shape were observed. The disruptant also showed a defect in cell wall integrity. An HA-Rho2 expressed in the cell was suggested to be present as a membrane-bound form by a cell fractionation experiment. A GFP-Rho2 was localized at the growing end(s) of the cell and the septation site. The localization of GFP-Rho2 during interphase was partially dependent on sts5+. These results indicate that Rho2 is involved in cell morphogenesis, control of cell wall integrity, control of growth polarity, and maintenance of growth direction. Analysis of functional overlapping between Rho2 and Rho1 revealed that their functions are distinct from each other, with partial overlapping.

CDC2 Protein Kinase↗
PubMed1998

Mutations in CLCN5 chloride channel in Japanese patients with low molecular weight proteinuria.

Mutations in the CLCN5 gene have been demonstrated in three disorders of hypercalciuric nephrolithiasis, i.e., Dent's disease, X-linked recessive nephrolithiasis, and X-linked recessive hypophosphatemic rickets. Recently, a number of Japanese children with low molecular weight proteinuria (LMWP) showing symptoms similar to those shown by patients with Dent's disease in British families have also been reported to have mutations in the CLCN5 gene. The present study examines five unrelated Japanese families with LMWP, two of which lacked any signs other than LMWP, and three of which had several signs other than LMWP, i.e., hypercalciuria, aminoaciduria, hypophosphatemia, and rickets. One nonsense (E118X) and one missense (W22G) mutation were found in three patients in the two families having only LMWP. One genomic deletion including exons 5 to 8 in the CLCN5 gene was found in a patient with hypophosphatemic rickets, and a nonsense mutation (R347X) was found in one patient with LMWP and slight hypercalciuria. No mutations of the exons and exon-intron boundaries in the CLCN5 gene were found in one patient with LMWP, aminoaciduria, and hypokalemia. In addition to the predicted loss of chloride channel function in these nonsense and deletion mutations, the loss of function in the missense mutation W22G was confirmed in the Xenopus oocyte expression system. These results clarified four novel mutations in the CLCN5 genes, and additionally suggested that the loss-of-function mutation of the CLCN5 does not necessarily lead to hypercalciuria and nephrocalcinosis in the early stage of the disease, and that LMWP is an early and essential manifestation of disorders of the CLC-5 chloride channel.

Adult↗