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Biomedical subjects

M Fukui

Publications and source records attributed to M Fukui.

At least 325 records · Page 18Linked to original sources

Relationship between hepatic iron deposits and response to interferon in chronic hepatitis C.

OBJECTIVES: The response to interferon in chronic hepatitis C is believed to be affected by hepatic iron content. We histopathologically examined liver biopsy specimens from patients with chronic hepatitis C to determine whether the presence or absence of hepatic iron deposits correlated with the response to interferon. METHODS: Sixty-three patients with hepatitis C treated with interferon-alpha were examined. Liver biopsy specimens obtained just before treatment were sliced and stained with Perls' Prussian blue. Twenty patients had complete responses, 24 patients had transient responses, and 19 patients had no response. RESULTS: Iron deposits stained by Prussian blue were seen in hepatocytes, sinusoidal cells, and portal mesenchymal cells. The degree of hepatocytic and sinusoidal iron deposits did not correlate with the response to interferon. However, the degree of portal iron deposits did correlate with hepatic inflammation activity (tau = 0.55, p < 0.001) and the severity of liver fibrosis (tau = 0.60, p < 0.001), and it correlated negatively to the response to interferon (tau = -0.49, p < 0.001). CONCLUSIONS: The results suggest that portal iron deposits are a factor in the response to interferon. The presence of portal iron deposits seems to be related to a poor response.

Adult↗

Intracranial epidural abscess: late complication of allograft cranioplasty.

A case of intracranial epidural abscess, 20 years after allograftic cranioplasty was presented. The abscess was caused by bacterial implantation after a minor stab wound of the scalp over the cranioplastic plate. It seemed quite rare that the intarcranial abscess occurred 20 years after an allograftic cranioplasty.

Abscess↗

Purification and characterization of a medium chain acyl-coenzyme A synthetase.

Glycine conjugation is an important route of detoxification of many xenobiotic and endogenous carboxylic acids. A medium chain acyl-coenzyme A synthetase that catalyzes the first reaction of glycine conjugation was purified from bovine liver mitochondria by chromatographies on anion exchange, hydroxylapatite, affinity, and finally by gel filtration. The purified enzyme not only conjugates medium chain fatty acids, but also aromatic and arylacetic acids. The highest activity was shown with hexanoic acid. High activities were observed for benzoic acid derivatives with large alkyl and alkoxyl groups in the para- or meta-positions of the benzene ring. Ortho-substituted derivatives exhibited no activity. The enzyme was inhibited by iodoacetamide and salicylic acid, and activated by albumin. Salicylic acid was a competitive inhibitor of the enzyme, with an apparent Ki value of 37 microM. Enzyme activity increased 74% when the pH was raised from 7 to 10. Molecular weight of the purified medium chain acyl-coenzyme A synthetase was 65.5 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Animals↗

Validity of a random noise oscillation and body box system for the measurement of the respiratory impedance of small animals.

The accuracy and validity of a body box system which was developed for the measurement of airway and chest wall impedance in small animals such as canines was evaluated. Input impedance was calibrated using a resistance tube and the mouth flow sensing system was designed to be as symmetrical as possible such that the minimal common mode rejection ratio (CMRR) from 10 to 40 Hz was greater than 60 dB. The validity of this system using the resistance tube and inertant models indicated that the average error ratio for the input impedance and for the flow transfer function between the mouth and chest flow was within 3 and 0.5%, respectively. The location of the box pressure port near to the oscillatory flow inlet was shown to potentially give rise to errors in the measurement of the flow transfer factor due to the direct effects of the inflow. A distance of 60 cm was adopted in the present system, which proved to be sufficient to avoid this effect. It was concluded that the body box system which is described for small animals in the present study is appropriate for obtaining separate and accurate airway and tissue impedance data.

Airway Resistance↗

Chest flow during the initial inspiratory phase (V0.1) in pulmonary diseased patients.

We measured the chest flow 0.1 s after the onset of the inspiratory phase (V0.1) in patients with chronic pulmonary emphysema (CPE: n = 5), interstitial pneumonitis (IP: n = 5) and normal subjects (Nor: n = 5). The subjects sat in a body box and breathed air from outside of the body box. V0.1 was measured during rest and during maximal breathing (V0.1-rest, V0.1-max) and then these results were compared with P0.1 (P0.1 rest, P0.1-max) values. V0.1-rest was not significantly different between the three groups (Nor: 0.25 +/- 0.10, CPE: 0.27 +/- 0.06, IP: 0.26 +/- 0.06, l/s), whereas the P0.1-rest in IP patients was significantly greater than in normal subjects (Nor: 1.98 +/- 0.61, CPE: 3.00 +/- 0.80, IP: 3.60 +/- 0.68 hPa; P < 0.05 compared with normal). The V0.1-max in CPE and IP patients was significantly lower than in normal subjects (Nor: 3.66 +/- 1.16, CPE: 0.82 +/- 0.25, IP: 1.02 +/- 0.21 l/s, P < 0.05 compared with normal subjects (Nor: 3.66 +/- 1.16, CPE: 0.82 +/- 0.25, IP: 1.02 +/- 0.21 l/s, P < 0.05 compared with normal), whereas P0.1-max in IP patients was not significantly different with in normal subjects (Nor: 33.2 +/- 10.2, CPE: 9.8 +/- 3.7, IP: 19.5 +/- 3.4 hPa, P < 0.05 compared with normal, P < 0.05 compared with CPE). A simulation of the influence of the mechanical properties of the respiratory system on V0.1 and P0.1 using the Runge-Kutta method suggested that V0.1 was negatively affected by airway resistance but positively affected by chest wall and lung compliance. In contrast, the influence of respiratory mechanics on P0.1 was much less than on the V0.1, except for highly decreased lung compliance. In CPE patients, it was suspected that mechanical disorders might not simply be the determining factors of V0.1-max, but that limitations of the neuro-muscular drive due to chest wall deformity may also play a definitive role in the smaller V0.1-max. In contrast, it may be inferred that IP patients had to exert greater inspiratory effort as compared with the other two groups in order to maintain a similar V0.1-rest because of the increased airway resistance and decreased tissue compliance; thus these abnormal mechanical properties suppress the increase in the V0.1-max. It may be concluded that V0.1 is a good index of chest wall acceleration, which is determined by both the neuro-muscular drive and the mechanics of the respiratory system.

Aged↗

Hyperperfusion and hypermetabolism in brain radiation necrosis with epileptic activity.

We report a case of high uptake of 11C-methionine (MET), 18F-FDG (FDG) and 201Tl-Cl (Tl) in brain radiation necrosis. Twenty-one years previously, the patient had undergone surgery and radiation therapy consisting of 60-Gy for ependymoma in the anterior horn of the right lateral ventricle. The clinical features consisting of frequent seizures of the left face and arm suddenly appeared 2 wk before admission. MRI depicted a Tl and T2-prolonged lesion in the right frontal lobe. Abnormally high uptake in this area demonstrated by MET-PET, FDG-PET, Tl-SPECT or HMPAO-SPECT suggested the presence of a recurrent tumor. A craniotomy was then performed and an intraoperative electrocorticogram showed continuous epileptic spikes in the lesion. The epileptic foci were resected and the histological features of the lesion were consistent with radiation necrosis. After surgery, the seizures disappeared and the postoperative examinations with MET-PET, FDG-PET, Tl-SPECT and HM-PAO-SPECT no longer showed abnormally high uptake. Hypermetabolism and hyperperfusion related to epileptic fits are therefore thought to result in high uptake of MET, FDG and Tl in radiation necrosis.

Adult↗

Effect of probucol on mRNA expression of glomerular antioxidant enzymes in rat with subtotal nephrectomy.

OBJECTIVE: To investigate 1) the glomerular mRNA expression and protein activity of antioxidant enzymes (AOEs) including superoxide dismutase (SOD) and glutathine peroxidase (GSH-Px) and the glomerular content of lipid peroxide-malondiadehyde (MDA), 2) the effects of probucol (P), a potent antioxidant agent on these AOEs and MDA levels, in the chronic phase of subtotal nephrectomized rats. METHODS: The adult male Spregue-Dawley rats were randomly divided into three groups at the first week after subtotal renal ablation. Group 1 was sham rats (sham n = 8), group 2 underwent 5/6 nephrectomy without special therapy (5/6 Nx n = 8), and group 3 with 5/6 nephrectomy received probucol (5/6 Nxs+P n = 8) at a dose of 1% in the rat chow. At the 12th week after P was administrated, all of the rats were sacrificed to remove left kidney for the determination of glomerular level of MDA, activity of SOD, and GSH-Px, glomerular mRNA expression of AOEs by Northern blot analysis as well as a histological examination. RESULTS: In 5/6 Nx, serum cholesterol, proteinuria increased and creatinine clearance decreased progressively with age as compared with that in sham. Those abnormalities as well as glomerulosclerosis index (GI) ameliorated with the administration of probucol at the 12th week after subtotal nephrectomy [GI: sham 3.12 +/- 1.20, P < 0.01 vs 5/6 Nx 5/6 Nx 188.6 +/- 25.1; 5/6 Nx +/- P, 106.9 +/- 17.6, P < 0.05 vs 5/6 Nx]. The probucol therapy also significantly improved the decrease of glomerular Mn-SOD and GSH-Px both at mRNA level and protein activity and the increase of glomerular MDA content. CONCLUSIONS: We demonstrated a deficiency of glomerular AOEs in the chronic phase of remnant kidney, which may contribute to the progression of renal injury. The protective effects of probucol on both renal functional impairment and the development of glomerulosclerosis may be partially associated with improving surviving glomerular AOEs.

Animals↗

Studies on the metabolism of haloperidol (HP): the role of CYP3A in the production of the neurotoxic pyridinium metabolite HPP+ found in rat brain following ip administration of HP.

The levels of haloperidol (HP) and its pyridinium metabolite HPP+ were estimated in plasma and brain tissues of rats treated i.p. with HP (10 mg/kg). HP and HPP+ levels in plasma decreased linearly during the 0-3 hour period following drug administration. On the other hand, HPP+ levels in brain tissues increased gradually during the same period. HPP+ levels in brain tissues increased further when HP (10 mg/kg) was injected for three consecutive days. The formation of HPP+ also was studied in rat brain mitochondrial and liver microsomal preparations. Enzyme activity responsible for the conversion of HP to HPP+ was not found in brain mitochondria. Liver microsomal enzymes catalyzed the oxidation of HP and its tetrahydropyridine dehydration product HPTP to HPP+ with about the same efficiency. Studies employing several cytochrome P450 inhibitors and anti-cytochrome P450 antibodies were carried out in an effort to identify the forms of cytochrome P450 that are responsible for catalyzing the oxidation of HP and HPTP to HPP+. The formation of HPP+ in liver microsomes was strongly inhibited by ketoconazole and nifedipine and by an anti-CYP3A antibody. These results suggest that formation of HPP+ from HP and HPTP in rat liver microsomes is catalyzed mainly by CYP3A although the participation of other P450 forms cannot be ruled out.

Animals↗

Resting load regulates cytosolic calcium-force relationship of the contraction of bovine cerebrovascular smooth muscle.

1. We determined the effects of a change in preload, or resting load, on the development of force and on cytosolic calcium concentration ([Ca2+]i) during the contraction induced by high K+ depolarization and by the stable analogue of thromboxane A2, U-46619, using front-surface fluorometry and medial strips of bovine middle cerebral artery loaded with fura-2. 2. Increase in resting load of strips from 0.495 mN (low load; 0.85L(max)) to 1.98 mN (optimal load; L(max)) elevated resting levels of [Ca2+]i slightly, and, significantly, after a delay of a few seconds. The force developed by high K+ depolarization at resting load of 1.98 mN was much greater than that at a resting load of 0.495 mN (191.8% of that at 0.495 mN); however, there was no difference in [Ca2+]i elevation induced by high K+ depolarization between resting loads of 0.495 and 1.98 mN. 3. Both in the presence and absence of extracellular Ca2+, the force developed by U-46619 (0.1 microM) at resting load of 1.98 mN was also much greater than that at a resting load of 0.495 mN. Both in the presence and absence of extracellular Ca2+, there was no difference in the [Ca2+]i transients induced by U-46619 between two different resting loads. 4. The [Ca2+]i-force relationship during the contraction induced by high K+ depolarization was shifted to the left when the resting load was increased from 0.495 to 1.98 mN. At 0.495 mN resting load, this Ca(2+)-force relationship was shifted to the left by U-46619. This left-side shift of the curve by U-46619 was further enhanced by the increase in resting load from 0.495 to 1.98 mN. 5. The augmentation of force development induced by the change in resting load (from 0.495 to 1.98 mN) was not affected by a relatively specific inhibitor of protein kinase C, 1-(5-isoquinolinesulphonyl)-2-methylpiperazine dihydro-chloride (H-7; 10 microM). 6. We conclude that (1) at a given degree of [Ca2+]i elevation, the developed force induced by U-46619 was greater than that induced by high K+ depolarization, and (2) preload, or resting load (below optimal load), regulates contractile responsiveness of cerebrovascular smooth muscle to various stimulations, mainly by modulating the [Ca2+]i-force relationship, without affecting the extent of [Ca2+]i elevation. The results suggest the possibility that Ca(2+)-insensitive pathways may be involved in the stretch-dependent regulation of Ca2+ sensitivity of the contractile apparatus in smooth muscle.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Expression of vascular endothelial growth factor and its possible relation with neovascularization in human brain tumors.

To examine which growth factors correlate with neovascularization in human brain tumors, the mRNA levels of transforming growth factor alpha, transforming growth factor beta, basic fibroblast growth factor, and vascular endothelial growth factor (VEGF) genes were determined by a Northern blot analysis in surgically obtained human gliomas and meningiomas. The vascular development was determined by counting the number of microvessels which were immunostained with von Willebrand factor. We normalized the growth factor mRNA levels versus the glyceraldehyde phosphate dehydrogenase mRNA level. In the 17 gliomas and 16 meningiomas examined, the mRNA of transforming growth factors alpha and beta, basic fibroblast growth factor, and VEGF were expressed at various levels. Among those 4 growth factors, the mRNA levels of VEGF, but not those of transforming growth factors alpha and beta and basic fibroblast growth factor, correlated significantly with vascularity in both gliomas (correlation coefficient r = 0.499; P < 0.05) and meningiomas (correlation coefficient r = 0.779; P < 0.001). These findings thus suggest that VEGF may be a positive factor in tumor angiogenesis in both human gliomas and meningiomas.

Brain Neoplasms↗

Effects of antiplatelet drug dilazep dihydrochloride on anionic sites and extracellular matrix (ECM) components in glomerular basement membrane of STZ-induced diabetic rats.

A study of anionic sites in the glomerular basement membrane (GBM) of streptozotocin (STZ)-induced diabetic rats with or without treatment by an antiplatelet drug, dilazep dihydrochloride, is described. Expression of glomerular extracellular matrix (ECM) components was examined by immunofluorescence. Renal specimens were immersed in polyethyleneimine (PEI) as a cationic probe and then examined by electron microscopy. Renal specimens were also incubated with rabbit antirat type IV collagen, laminin, and fibronectin antisera and then stained with fluorescein isothiocyanate (FITC)-labeled goat antirabbit IgG antiserum. Mean values of proteinuria in the dilazep-treated diabetic rats were significantly decreased compared with those in nontreated diabetic rats. There was no significant correlation between the levels of proteinuria and those of creatinine clearance (CCr). Number of anionic sites on the GBM in the dilazep-treated diabetic rats were greater than those in diabetic rats. There was no significant difference in the staining of such ECM components between both rat groups. The authors concluded that the dilazep dihydrochloride might prevent anionic charges on the GBM and decrease the urinary excretion of proteins in STZ-induced diabetic rats.

Animals↗

Cranial fasciitis with massive intracranial extension.

The case of a 10-month-old boy with cranial fasciitis is described. The patient had a rapidly growing subcutaneous mass in the left frontotemporal region. Computed tomography and magnetic resonance imaging clearly demonstrated a mass in the left temporoparietal bone extending both intra- and extracranially. The tumor seemed to originate from the calvarium, being located between the periosteum and the dura mater. Total resection of the tumor was performed, and the tumor was histologically identified as cranial fasciitis. A brief review of the literature is included that emphasizes the need for further investigation of this benign lesion that is frequently confused with a malignant neoplasm.

Brain Diseases↗

Spontaneous resolution of hypertrophic cranial pachymeningitis.

A 36-year-old woman presented suffering from severe headache and diploia. Magnetic resonance imaging showed a diffuse thickening of the cranial dura mater which was enhanced by gadolinium-DTPA. Two months later, an improvement of the clinical symptoms and a spontaneous resolution of the dural thickening were noted. Hypertrophic cranial pachymeningitis and other diseases causing diffuse dural thickening are discussed.

Adult↗

Intracranial epidermoid carcinoma: CT and MRI.

We report a patient with an epidermoid carcinoma an extremely rare brain tumour, in the right cerebellopontine angle cistern. Contrast enhancement is the most important feature for differential diagnosis of epidermoid carcinomas from atypical benign epidermoid cysts.

Brain↗

Functional mapping of the sensorimotor cortex: combined use of magnetoencephalography, functional MRI, and motor evoked potentials.

Combined use of magnetoencephalography (MEG), functional magnetic resonance imaging (f-MRI), and motor evoked potentials (MEPs) was carried out on one patient in an attempt to localise precisely a structural lesion to the central sulcus. A small cyst in the right frontoparietal region was thought to be the cause of generalised seizures in an otherwise asymptomatic woman. First the primary sensory cortex was identified with magnetic source imaging (MSI) of somatosensory evoked magnetic fields using MEG and MRI. Second, the motor area of the hand was identified using f-MRI during hand-squeezing. Then transcranial magnetic stimulation localised the hand motor area on the scalp, which was mapped onto the MRI. There was a good agreement between MSI, f-MRI and MEP as to the location of the sensorimotor cortex and its relationship to the lesion. Multimodality mapping techniques may thus prove useful in the precise localisation of cortical lesions, and in the preoperative determination of the best treatment for peri-rolandic lesions.

Adult↗

Calcified convexity dura mater and acute epidural haematoma mimicking calcified chronic subdural haematoma.

We report a patient with calcification of the convexity dura mater and an acute epidural haematoma. CT revealed a calcified layer between the haematoma and brain parenchyma, which mimicked acute bleeding into a calcified chronic subdural haematoma. The appearance of a calcified haematoma does not always mean a "chronic" lesion, and that emergency operation should not be foregone, when there is a history of acute head trauma and progressive impairment of consciousness.

Acute Disease↗