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Biomedical subjects

M Fukui

Publications and source records attributed to M Fukui.

At least 163 records · Page 9Linked to original sources
PubMed1999

Influence of TNF microsatellite polymorphisms (TNFa) on age-at-onset of insulin-dependent diabetes mellitus.

The TNF-alpha gene is located in the HLA region and has been implicated in the pathogenesis of Type I (insulin-dependent) diabetes mellitus (IDDM). We investigated the frequency of TNFa microsatellite alleles in 76 young-onset IDDM patients, 65 adult-onset IDDM patients, and 90 control subjects. We also examined the association of these TNFa alleles with HLA-DRB1 alleles, HLA-class I alleles, and TNF-alpha production. The frequency of the TNFa2 and TNFa9 alleles was increased in the young-onset IDDM patients compared to control subjects, but the increased frequency of TNFa2 was not significant after the correction for the number of comparisons was made. We did not find any association of TNFa2 or TNFa9 with any of the HLA-DRB1 alleles. In contrast, the frequency of the TNFa13 allele was decreased in both the young-onset and the adult-onset IDDM patients compared to the control subjects, but the difference lost significance after the correction was made in the adult-onset IDDM. The TNFa13 allele was strongly associated with DRB1*1502. Patients with TNFa2 or TNFa9 had greater TNF-alpha production, while those positive for TNFa13 had lower TNF-alpha production than patients with non-TNFa2, a9, and a13 alleles. These results suggest that TNFa polymorphisms are associated with age-at-onset of IDDM and influence the inflammatory process of pancreatic beta cell destruction in the development of IDDM.

Adolescent↗
PubMed1999

Intrinsic epileptogenicity of focal cortical dysplasia as revealed by magnetoencephalography and electrocorticography.

Focal cortical dysplasia (FCD) is often associated with severe partial epilepsy. In this study, we performed magnetoencephalography (MEG) and electrocorticogrsphy (ECoG) on four patients with FCD-associated epilepsy to confirm the 'intrinsic' epileptogenicity of FCD. In all patients, we determined the three-dimensional locations of the magnetic sources of the interictal paroxysmal activities by a single dipole model, and then the estimated dipole localization was superimposed on the magnetic resonance image. The dipole clusters were located in the T2-prolonged lesions, namely in the FCD lesions themselves. All patients underwent surgery for their medically intractable epilepsy, and the acute and/or chronic ECoG were thereafter recorded. Either frequent or continuous paroxysmal activities were recorded from the ECoG electrodes which were placed over the surface of the FCD lesion, while few paroxysmal activities were observed on the normal appearing adjacent cortex. Intraoperative depth recordings were performed in a patient with the needle electrode inserted into the FCD lesion and they revealed these paroxysmal foci to be located not on the cortical surface but at a depth of 15 mm from the cortical surface where both abnormal giant neurons and bizarre large eosinophilic cells (so-called balloon cells) were also prominently observed on the postoperative histological sections. Following a lesionectomy combined with the removal of the underlying white matter, three patients demonstrated a favorable seizure outcome. Our findings thus suggest the FCD lesions to be highly and intrinsically epileptogenic lesions.

Adult↗
PubMed1999

Distribution of brainstem somatosensory evoked potentials following upper and lower limb stimulation.

OBJECTIVE: Because somatosensory evoked potentials (SEP) to lower limb stimulation have not been recorded from the brainstem to the extent that upper limb SEPs have been studied, we compared brainstem recordings in response to both median nerve (MN) and posterior tibial nerve (PTN)stimulation. METHODS: SEPs were recorded directly from the dorsal surface of the brainstem in four patients with fourth ventricle tumors. RESULTS: Following MN stimulation, medullary SEPs were characterized by a major negativity (N1) preceded by a small positivity (P1) and followed by a large positivity (P2). In the pons, triphasic waves with predominant negativity were obtained. With PTN stimulation, similar medullary SEPs with a P1'-N1'-P2' configuration and pontine SEPs with a triphasic waveform were obtained. CONCLUSIONS: Since the distribution of PTN SEP was identical to that of MN SEP, PTN SEPs are thought to be generated by mechanisms similar to those for MN SEP. Thus, the P1' and N1' of medullary SEP would be generated by the dorsal column fibers that terminate in the nucleus, with P2' possibly arising postsynaptically in the nucleus. The triphasic PTN SEP from the pons reflects an axonal potential generated in the medial lemniscal pathway.

Adult↗
PubMed1999

Selective transvascular delivery of oligodeoxynucleotides to experimental brain tumors.

Optimal therapeutic strategy for malignant brain tumors is controversial. Recent studies of viral or nonviral gene therapy in rats emphasize the need for a selective delivery system. We examined whether phosphorothioate oligodeoxynucleotides (lacZ 2157, 5'-GTGGCGTCTGGCGGAAAACC-3') could be selectively delivered transvascularly into experimental brain tumors following intracarotid infusion of bradykinin, a specific blood-tumor barrier opener. The specificity of 32P-labeled complementary antisense lacZ 2157 and the stability of lacZ 2157 in vivo were confirmed using slot-blotting hybridization method and polyacrylamide gel electrophoresis. Concentrations of lacZ 2157 after intracarotid injection (2 mg/kg, 10 microg/kg/min) with or without bradykinin were determined in the brain, tumor tissue, liver, kidney, and plasma. The transfer ratio of lacZ 2157 from the plasma to the tissues was calculated and expressed as tissue content relative to plasma content of lacZ 2157 per mg tissue (Do, microl/mg). Delivery of lacZ 2157 to tumor tissue increased 3.24 times with bradykinin over delivery in controls (0.0243 +/- 0.0176 vs. 0.00750 +/- 0.00389; p < 0.05). Delivery of lacZ 2157 to ipsilateral and contralateral cerebral cortex to the tumor, and delivery to the contralateral basal ganglia, did not increase significantly with bradykinin. These results indicate that such transvascular delivery with bradykinin can deliver a relatively large amount of oligodeoxynucleotide selectively to brain tumors without affecting normal brain.

Animals↗
PubMed1999

Overproduction of elongation factor 1alpha, an essential translational component, causes aberrant cell morphology by affecting the control of growth polarity in fission yeast.

BACKGROUND: Elongation factor 1alpha (EF1alpha), an essential component of the eukaryotic translational machinery, has been shown to possess various biochemical and biological activities, including F-actin-binding and -bundling, microtubule- severing, and the activity of making fibroblasts highly susceptible to transformation. However, our understanding of the biological significance of EF1alpha with respect to these various biochemical or biological activities remains limited. Here we report the identification of EF1alpha-encoding genes as genes whose over-expression causes aberrant cell morphology in fission yeast. RESULTS: Overproduction of EF1alpha caused aberrant cell morphology-elliptic, curved or branched-and growth defects in yeast cells at high temperatures. EF1alpha-overproducing cells showed a supersensitivity to the actin inhibitor cytochalasin D and to the tubulin inhibitor thiabendazole. Genetic analyses using cdc mutants suggested that excess EF1alpha disturbed the establishment and the maintenance of growth polarity in the G1 phase by pre- venting the localization of F-actin to the polarized growing site and the organization of microtubules. Results from DNase I column chromatography indicated that EF1alpha was bound to G-actin. Indeed, the fission yeast actin was immunoprecipitated along with EF1alpha. Moreover, the temperature sensitivity caused by the overproduction of EF1alpha was restored by co-overproduction of actin. CONCLUSIONS: Fission yeast EF1alpha has the ability to alter the cell morphology of yeast by affecting the control of actin and microtubule cytoskeletons.

Actins↗
PubMed1999

Immunohistochemical expression of trk receptor proteins in focal cortical dysplasia with intractable epilepsy.

Focal cortical dysplasia (FCD), which is often associated with intractable epilepsy, is a form of abnormal structure of the cerebral cortex caused by a disorder of normal neocortical development. In such cerebral lesions obtained from four patients (two male, two female; average age 32.3 years at operation), the immunohistochemical expression of Trk receptors, which interact with neurotrophins and result in both growth and maturational changes in neuronal cells, was investigated in relation to the possible histogenesis of these lesions. In all cases, a derangement of the cortical laminar structure, dysplastic cytomegalic neurones, and large round balloon cells were the characteristic histological features. Immunohistochemically, the TrkA expression was localized in large dysplastic cytomegalic neurones, and TrkB expression was observed in large dysplastic and relatively small neuronal cells within the affected cortex. Although the exact roles of neurotrophins and their receptors in the pathogenesis of FCD remain uncertain, its development might be governed by such neurotrophic influences, and thus possibly prevent the death of abnormal neuronal cells. In addition, Trk receptors in FCDs may also play a role in establishing in the intrinsic epileptogenicity of FCDs.

Adult↗
PubMed1999

Pituitary abscess secondary to isolated sphenoid sinusitis.

Intracranial complications from isolated sphenoid sinusitis are rare but nevertheless demonstrate both a high morbidity and mortality. We herein report a case of a pituitary abscess secondary to sphenoid sinusitis in a 12-year-old boy. This patient presented with an acute onset of moderate fever and headache, followed by progressive right ptosis. An emergency endoscopic endonasal sphenoidotomy with sinus drainage and postoperative antibiotic therapy resulted in a satisfactory recovery.

Brain Abscess↗
PubMed1999

Role of inducible nitric oxide synthase in the cerebral vasospasm after subarachnoid hemorrhage in rats.

The involvement of de novo nitric oxide synthase (NOS) induction in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH) was examined using a rat model of SAH. SAH was induced by endovascular perforation with Nylon thread. The rats were killed at different time intervals, from one day to seven days after endovascular perforation. Inducible NOS messenger RNA (mRNA) expression was determined by reverse-transcription polymerase chain reaction (RT-PCR) and the distribution of iNOS positive cells was immunohistochemically examined. In the vascular tissue with a subarachnoid membrane, iNOS mRNA was expressed from one day to seven days after SAH. Inducible NOS positive cells were mainly recognized in the vascular tissue, but not in the brain parenchyma. The distribution of nitrotyrosine, an indicator of peroxynitrite production was also examined immunohistochemically and nitrotyrosine-positive cells were observed almost at the same sites of iNOS induction. To determine the role of iNOS in the development of cerebral vasospasm, we measured the diameter of the middle cerebral artery in animals either treated or not treated with aminoguanidine (AG), a selective inhibitor of iNOS. AG ameliorated the vasoconstrictive change after SAH. These results are thus considered to provide molecular and immunohistochemical evidence showing that iNOS expression following SAH and NO produced by iNOS can develop cerebral vasospasm after SAH.

Animals↗
PubMed1999

Effect of intracarotid bradykinin infusion on cerebral blood flow in dogs.

We examined whether intracarotid infusion of bradykinin altered circulation in the normal canine brain. Twenty-four anesthetized dogs were divided into four groups receiving different doses of bradykinin (1, 2.5, 5, and 10 micrograms kg-1 min-1). Regional cerebral blood flow (rCBF) was measured continuously using laser Doppler flowmetry through a burr hole in the frontal bone. Systemic blood pressure (SBP) and heart rate (HR) were monitored simultaneously. Higher doses of bradykinin significantly but temporarily decreased rCBF and SBP immediately after the start of infusion; these parameters rapidly recovered and then were stable through the rest of the infusion. During this period, percent change in rCBF and SBP was small, and differences between groups were not significant. On the other hand, HR increased during infusion and remained high. SBP, rCBF, and HR returned to pre-infusion levels after bradykinin was stopped. The results suggest that intracarotid infusion of bradykinin for treatment of brain tumors would be safe in terms of circulation to the uninvolved brain.

Animals↗
PubMed1999

Mapping of a familial moyamoya disease gene to chromosome 3p24.2-p26.

Moyamoya disease is characterized by bilateral stenosis and/or occlusion of the terminal portion of the internal carotid artery. Moyamoya disease is prevalent among patients <10 years of age. Although most cases appear to be sporadic, approximately 10% occur as familial cases. The incidence of familial cases has been increasing because noninvasive diagnostic equipment, such as magnetic-resonance imaging and magnetic-resonance angiography, can detect the disease in almost all affected patients, including asymptomatic patients, during screening studies. In this study, we performed a total genome search to identify the location of a familial moyamoya disease gene in 16 families, assuming an unknown mode of inheritance. A linkage was found between the disease and markers located at 3p24.2-26. A maximum NPL score of 3.46 was obtained with marker D3S3050. This is the first genetic locus found to be involved in the molecular pathogenesis of familial moyamoya disease.

Base Sequence↗
PubMed1999

Human chorionic gonadotrophin in CSF, not serum, predicts outcome in germinoma.

OBJECTIVES: Some intracranial germinomas, which may contain syncytiotrophoblastic giant cells (STGCs), are associated with a mildly to moderately increased human chorionic gonadotropin (HCG) concentration in serum, and patients with such germinomas are thus treated more aggressively than those with "pure" germinoma. However, the patients with germinoma and detectable HCG in CSF but not in serum have been classified and treated similarly to those with "pure" germinomas. The outcome of these patients and the relevance of HCG in the CSF were analysed. METHODS: The outcomes of patients with germinoma and increased serum HCG concentration (n=7) were compared with those of patients having detectable HCG titre in the CSF but not in the serum (n=5). RESULTS: Both groups in our series received similar treatments and also showed similar recurrence rates. The 40% recurrence rate in the group with HCG only in CSF did not correspond to the rate typical for "pure" germinoma: these tumours would be expected to have a better outcome. An additional patient whose CSF HCG were raised without increased serum HCG at recurrence is presented. CONCLUSIONS: It is recommended that patients with an increased HCG concentration in CSF should be considered to have "HCG producing germinoma", and they should be treated and followed up accordingly.

Adolescent↗
PubMed1999

Acute response of the lung mechanics of the rabbit to hypoxia.

We measured the change in total lung resistance (RL) and that in total lung elastance (EL) induced by hypoxia (n = 7) and compared the results with those by intravenous histamine bolus (n = 5) at three different positive end-expiratory pressure (PEEP) levels (2, 5, and 8 hPa) in open-chest and vagotomized rabbits. The percent increase ratio of RL (PIRR) and EL (PIRE) was defined as the change in RL and EL, respectively, induced by hypoxia compared with that in the normoxic condition, expressed as a percentage. PIR values for the change in RL and EL induced by bolus injection of histamine were also calculated. The PIRR and PIRE induced by hypoxia and by histamine were positive by a statistically significant amount at every PEEP level, except for the PIRE value at 8-hPa PEEP in the hypoxic challenge. The PIRE-to-PIRR ratio values in the hypoxic challenge at 2-hPa PEEP were significantly larger than those in the histamine challenge (hypoxia: 0.91 +/- 0.23%; histamine: 0.37 +/- 0. 065%, P < 0.05). The increase in EL induced by histamine in the acute phase has been reported to be mainly derived from tissue distortion secondary to bronchial constriction. Thus our results suggest that a part of the increase in EL by hypoxia was originated in different parenchymal responses from histamine and imply that this hypoxic response of lung parenchyma is sensitive to the increase in parenchymal tethering at high PEEP levels.

Airway Resistance↗
PubMed1999

Serum levels of soluble Fas and disease activity in patients with IgA nephropathy.

Using a sandwich ELISA, we studied 48 patients with IgA nephropathy and 10 patients with diffuse mesangial proliferative glomerulonephritis without IgA deposition (non-IgA PGN) to determine if levels of serum soluble Fas (s-Fas) might reflect the disease activity. The levels of serum s-Fas in patients with the advanced stage of IgA nephropathy were significantly higher than those in patients with the mild stage of the disease, in non-IgA PGN or in healthy controls. The results showed that advanced stage IgA nephropathy patients who showed heavy proteinuria and the presence of urinary casts revealed high levels of serum s-Fas. It was thus suggested that the measurement of serum s-Fas is useful in evaluating the degree of renal injury in patients with IgA nephropathy.

Adolescent↗
PubMed1999

Three-dimensional reconstruction system for imaging of the temporomandibular joint using magnetic resonance imaging.

This study was undertaken to develop a three-dimensional reconstruction system using magnetic resonance (MR) images in order to visualize three-dimensional images of the temporomandibular joint (TMJ) including the disk. The computerized reconstruction program (written using Visual Basic for Windows, Microsoft Corp.) could reliably generate three-dimensional images of the TMJ. Image processing techniques made the tracing of images unnecessary, reduced complex human manipulation and associated measurement errors. This system, capable of treating fifty thousand pixels or more, generates smooth three-dimensional images of the TMJ.

Data Display↗