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Biomedical subjects

M Fukui

Publications and source records attributed to M Fukui.

At least 307 records · Page 17Linked to original sources
PubMed1996

Enhanced tumor uptake of carboplatin and survival in glioma-bearing rats by intracarotid infusion of bradykinin analog, RMP-7.

OBJECTIVE: Intracarotid infusion of the bradykinin analog, RMP-7, can increase permeability in brain tumor capillaries. This study sought to determine the following: 1) the unidirectional transport, Ki, of radiolabeled [14C]carboplatin into brain tumors with either intravenous or intracarotid RMP-7 infusions; 2) the duration and extent of increased permeability in tumor capillaries during continuous RMP-7 infusions; and 3) the effect on survival of carboplatin combined with RMP-7 treatment in rats with gliomas. METHODS: Wistar rats with RG2 gliomas were used, and a unidirectional transfer constant, Ki, was determined using quantitative autoradiography. In the survival study, the rats were treated with intra-arterial carboplatin and RMP-7 at Days 5 and 7 after tumor implantation. RESULTS: Intracarotid infusion of RMP-7 for 15 minutes increased the transport of [14C]carboplatin to tumors by 2.7-fold, as compared with saline infusion alone (P < 0.001). The transports of [14C]dextran and [14C]carboplatin into tumors were significantly higher with 15 minutes of intracarotid infusion of RMP-7 (0.1 microgram/kg/min), compared to those with 10-, 30-, or 60-minute infusions (P < 0.01). Rats treated at Days 5 and 7 after tumor implantation with carboplatin alone (10 mg/kg) exhibited a modest increase in survival at 31 days (37%, compared to < 10% of controls), while those given the combination of carboplatin with RMP-7 exhibited a significantly higher survival rate (74%). CONCLUSION: Intracarotid infusion of RMP-7 can selectively increase transport of carboplatin into brain tumors and results in higher survival in rats with gliomas. These findings support the use of intracarotid infusion of RMP-7 to enhance the delivery of carboplatin to patients with malignant brain tumors.

Animals↗
PubMed1996

Dual regulation of cerebrovascular tone by UTP: P2U receptor-mediated contraction and endothelium-dependent relaxation.

1. The mechanisms of vascular tone regulation by extracellular uridine 5'-triphosphate (UTP) were investigated in bovine middle cerebral arterial strips. Changes in cytosolic Ca2+ concentration ([Ca2+]i) and force were simultaneously monitored by use of front-surface fluorometry of fura-2. 2. In the arterial strips without endothelium, UTP (0.1 microM-1 mM) induced contraction in a concentration-dependent manner. However, when the endothelium was kept intact, cumulative application of UTP (0.1-100 microM) (and only at 1 mM) induced a modest phasic contraction in arterial strips. This endothelium-dependent reduction of the UTP-induced contraction was abolished by 100 microM N omega-nitro-L-arginine (L-NOARG) but not by 10 microM indomethacin. In the presence of intact endothelium, UTP (30 microM) induced a transient relaxation of the strips precontracted with 30 nM U-46619 (a stable analogue of thromboxane A2), which was completely inhibited by pretreatment with L-NOARG but not with indomethacin. 3. In the endothelium-denuded strips, the contractile response to UTP was abolished by desensitization to either ATP gamma S or ATP (P2U receptor agonists), but not by desensitization to alpha, beta-methylene-ATP (P2x receptor agonist) or to 2-methylthio-ATP (P2Y receptor agonist). Desensitization to UTP abolished the contractile response to ATP. 4. In the endothelium-denuded artery, a single dose application of UTP induced an initial transient, and subsequently lower but sustained increase in [Ca2+]i and force. In the absence of extracellular Ca2+, UTP induced only the initial transient increases in [Ca2+]i and force, while the sustained increases in [Ca2+]i and force were abolished. UTP (1 mM) had no effect on the basic [Ca2+]i-force relationship obtained on cumulative application of extracellular Ca2+ at steady state of 118 mM K(+)-depolarization-induced contraction. 5. We conclude that in the presence of an intact endothelium, UTP-induced relaxation of preconstricted middle cerebral artery is mainly mediated indirectly, by the production of an endothelium-derived relaxing factor, but at high doses of UTP, vascular smooth muscle contraction is mediated directly via activation of P2U purinoceptor and [Ca2+]i elevation without Ca(2+)-sensitization of the contractile apparatus. UTP may thus exert a dual regulatory effect upon cerebrovascular tone, but in cases where the endothelium is impaired, it may also act as a significant vasoconstrictor.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Pharmacokinetic study of zonisamide in patients undergoing brain surgery.

To test whether the concentration of the anticonvulsant zonisamide in erythrocytes reflects the brain concentration and the clinical response of the drug, its pharmacokinetics were studied in nine patients undergoing surgery for brain tumour. Erythrocyte, total and free serum concentrations in samples drawn on the day of brain surgery were compared with levels on a day after the operation. In three patients zonisamide and its major metabolite, 2-sulphamoylacetylphenol, were also analysed in urine. The area under the curve of the free and the erythrocyte concentration did not differ between the two study phases whereas the area under the curve of the total serum concentration was significantly lower on the day of the operation, and this was associated with significant increases in total clearance (15.4 compared with 12.7 mL kg-1 h-1, P < 0.05, n = 9) and renal clearance (5.4 compared with 3.3 mL kg-1 h-1, P < 0.05, n = 3), and non-significant change in non-renal clearance (7.7 on the day of operation compared with 8.4 mL kg-1 h-1 on the post-operation day, n = 3). Zonisamide distribution was also altered by the operative procedure, as evidenced by a higher volume of distribution (1.48 compared with 0.87 L kg-1, P < 0.05, n = 9). The binding of zonisamide was characterized on both days. Zonisamide binding to erythrocytes seemed to occur by two processes: a saturable process and a non-saturable linear process. The maximum binding capacity to erythrocytes (31.6 vs 29.7 micrograms mL-1) did not differ on the two days; however, increases in the dissociation binding constant (+28%) and the proportionality constant (+24%) were observed on the day of the operation, suggesting that the zonisamide concentration in erythrocytes was greater on the day of the operation. Brain surgery appears to be one of the possible factors altering the rate of elimination of zonisamide and the uptake of the drug by erythrocytes.

Adult↗
PubMed1996

Degradative capacities and 16S rRNA-targeted whole-cell hybridization of sulfate-reducing bacteria in an anaerobic enrichment culture utilizing alkylbenzenes from crude oil.

A mesophilic sulfate-reducing enrichment culture growing anaerobically on crude oil was used as a model system to study which nutritional types of sulfate-reducing bacteria may develop on original petroleum constituents in oil wells, tanks, and pipelines. Chemical analysis of oil hydrocarbons during growth revealed depletion of toluene and o-xylene within 1 month and of m-xylene, o-ethyltoluene, m-ethyltoluene, m-propyltoluene, and m-isopropyltoluene within approximately 2 months. In anaerobic counting series, the highest numbers of CFU (6 x 10(6) to 8 x 10(6) CFU ml-1) were obtained with toluene and benzoate. Almost the same numbers were obtained with lactate, a substrate often used for detection of the vibrio-shaped, incompletely oxidizing Desulfovibrio sp. In the present study, however, lactate yielded mostly colonies of oval to rod-shaped, completely oxidizing, sulfate-reducing bacteria which were able to grow slowly on toluene or crude oil. Desulfovibrio species were detected only at low numbers (3 x 10(5) CFU ml-1). In agreement with this finding, a fluorescently labeled, 16S rRNA-targeted oligonucleotide probe described in the literature as specific for members of the Desulfovibrionaceae (suggested family) hybridized only with a small portion (< 5%) of the cells in the enrichment culture. These results are consistent with the observation that known Desulfovibrio species do not utilize aromatic hydrocarbons, the predominant substrates in the enrichment culture. All known sulfate-reducing bacteria which utilize aromatic compounds belong to a separate branch, the Desulfobacteriaceae (suggested family). Most members of this family are complete oxidizers. For specific hybridization with members of this branch, the probe had to be modified by a nucleotide exchange. Indeed, this modified probe hybridized with more than 95% of the cells in the enrichment culture. The results show that completely oxidizing, alkylbenzene-utilizing sulfate-reducing bacteria rather than Desulfovibrio species have to be considered in attempts to understand the microbiology of sulfide production in oil wells, tanks, and pipelines when no electron donors other than the indigenous oil constituents are available.

Anaerobiosis↗
PubMed1996

Differential expression of CD44 variants among meningioma subtypes.

Aims/background-CD44 is a widely distributed cell surface molecule which has numerous isoforms generated by alternative splicing. The diverse functions related to the CD44 variants (CD44v) have been reported in various physiological and pathological conditions. The pattern of expression of CD44v among meningioma subtypes was investigated to ascertain whether CD44 variants play a role in a variety of biological processes, such as epithelial differentiation and extracranial metastasis.Methods-Twenty three meningiomas were studied immunohistochemically using novel antibodies directed against CD44 isoforms. Six of the 23 samples were analysed by reverse transcription polymerase chain reaction (RT-PCR), followed by Southern blotting with CD44v specific probes.Results-In meningothelial, fibrous and anaplastic meningiomas, a standard form of CD44 was detected by RT-PCR and was homogeneously expressed in tumour cells when studied immunohistochemically. CD44v was not detected in these subtypes. In secretory meningiomas, however, CD44v isoforms were strongly expressed in the cell clusters that produce secretory granules and also accumulated in the granules. The population of tumour cells immunopositive for CD44v was similar to that which stained with antibodies directed against carcinoembryonic antigen, epithelial membrane antigen and ezrin. On RT-PCR with Southern blotting, only the secretory type showed high level expression of CD44v.Conclusions-CD44v in meningiomas is expressed in relation to tumour cell differentiation towards the epithelial type.

Journal Article↗
PubMed1996

Hypoxic contraction of contractile interstitial cells isolated from bovine lung.

Although contractile interstitial cells (CIC) in the alveolar septum have been suggested to be involved in hypoxic pulmonary vasoconstriction (HPV), direct demonstration of cellular contraction under hypoxia has been lacking. To achieve this, we purified CIC from collagenase-dissociated bovine lung cells and examined the response of these cells to hypoxia. Prostaglandin (PG) F synthase served as a marker of CIC, and the isolated PGF synthase-positive cells were shown to preserve the ultrastructural features characteristic of CIC, most notably bundles of microfilaments. Isolated CIC seeded onto collagen gel disks became embedded and formed a lattice network with collagen fibrils. Exposure of these CIC-bearing gels to hypoxia (PO2 = 20-40 Torr) evoked a reversible reduction in gel volume, as assessed by measuring the surface area of the gel disks photographically. Thus CIC were shown to contract under hypoxia, providing the supportive evidence for the involvement of CIC in HPV.

Animals↗
PubMed1996

Inhibitory effect of an intellectual task on breathing after voluntary hyperventilation.

We investigated the effects of an intellectual task on posthyperventilation (PHV) breathing by using a video game. Eight normal subjects were placed in a supine positions. The game task by itself led to increase ventilation compared with the control tasks via an increase in the average inspiratory flow rate (P < 0.01) and the respiratory frequency (P < 0.001). After hypocapnic voluntary hyperventilation (VHV), the task led to a decrease in the 1-min PHV breathing level compared with the control tasks after VHV [after VHV, first 60 s average minute ventilation while watching television and while playing a video game are 5.54 +/- 2.91 (SD) and 2.05 +/- 1.40 l/min, respectively; P < 0.01]. Only one subject showed PHV apnea for at least 10 s during the control protocol, whereas seven of the same eight subjects showed PHV apnea while performing the task. After isocapnic VHV, the task still led to a decrease in PHV breathing compared with the control tasks. However, this decrease was smaller than in the hypocapnic studies and was only significant during the first 15 s of recovery. These results suggest that increased activity in the higher centers of the central nervous system has an inhibitory effect on PHV breathing at a time when the effects of short-term potentiation after VHV, hypocapnia, and perhaps other mechanisms would be expected to be acting on breathing.

Adult↗
PubMed1996

Surgical control of akinesia in Parkinson's disease.

Posteroventral pallidotomy (PVP) was carried out in 86 patients with Parkinson's disease, who presented marked bradykinesia, freezing of gait and postural defect associated with rigidity and tremor in 82 patients (bradykinesia type), and similar gait and postural problems with minimum signs of rigidity and tremor in 4 (pure akinesia type). The stereotactic coordinates of Leksell's device were calculated from MRI and conventional ventriculography. The final target was defined by microelectrode techniques in the basal ganglia. The microrecording study revealed a very high background activity in the internal pallidum in patients of the bradykinetic type, however, a much lower pallidal activity in patients of the pure akinesia type. Fifty-eight patients underwent unilateral PVP, and 28 underwent bilateral surgery. Following PVP, rigidity tremor and poor reciprocal movements were significantly improved especially in the contralateral extremities. The most dramatic findings were the reversal of akinetic symptoms and wearing-off phenomena. The patients were followed up for 3-30 months (mean = 8) after surgery. Of the 82 bradykinesia type patients, good result were obtained in 48 (58%), fair results in 26 (32%), and minor improvement or no change in 8 (10%). In all the 4 patients of the pure akinesia type, recurrence of the akinetic symptoms occurred after a temporal improvement lasting a few days to 3 month after surgery. There was worst dysarthria in 3 patients, hemiparesis in 1 and partial motor aphasia in 1. The visual field problem was not complicated in any patients. These findings suggest that akinetic symptoms in PD are implicated in overactive pallidal outputs with putative GABAergic modulator by excessively inhibiting pedunculopontine nucleus activity (midbrain locomotor and posture regions) as well as thalamic activity. Partial interruption of the pallidal efferents eliminates the akinetic symptoms by disinhibitory effects on the target structures. The pathology of PD of the pure akinesia type is supposedly in the brainstem and should be excluded from indication of pallidotomy.

Adult↗
PubMed1996

Increased secretion of triglyceride and cholesterol following inhibition of long-chain fatty acid oxidation in rat liver.

The effects of emeriamine, a fungal metabolite and a potent inhibitor of mitochondrial fatty acid oxidation, on ketogenesis and lipid secretion were examined in isolated perfused livers from 2-day-fasted rats. Liver perfusion with increasing concentrations of emeriamine up to 3 mumol caused a dose-dependent inhibition of ketone body production. The hepatic uptake of exogenous oleic acid substrate was comparable in the control and emeriamine-treated livers. The addition of 2 mumol emeriamine to the perfusion medium at either the beginning of perfusion or 2 h later caused immediate and almost complete cessation of ketone body production, which was accompanied by a concomitant decrease in the beta-hydroxybutyrate: acetoacetate ratio, suggesting a decreased production of NADH via mitochondrial beta-oxidation. Conversely, both triglyceride and cholesterol secretions were elevated, indicating a reciprocal response in ketogenesis and lipid secretion by the livers. The proportion of oleate in the perfusate triglyceride obtained from emeriamine-treated livers was significantly higher than that from control livers. In the post-perfused liver triglyceride, oleate was progressively increased in the livers treated with the inhibitor 2 h after perfusion and at the beginning of perfusion, respectively. These results indicate that direct inhibition of fatty acid oxidation diverts the exogenous fatty acids to the esterification pathway, and subsequently stimulate the synthesis and secretion of triglyceride and cholesterol. The fatty acid oxidation rate in the liver is, therefore, a critical determinant for the synthesis and secretion of these lipid components.

3-Hydroxybutyric Acid↗
PubMed1996

Effect of a specific endothelin receptor A antagonist on glomerulonephritis of ddY mice with IgA nephropathy.

The present study assessed renal endothelin (ET)-1, ET-3, and ET receptor A and B mRNA levels in ddY mice at 8, 40, and 60 weeks of age. The renal mRNA levels of ET-1 increased significantly in ddY mice as their nephritis progressed, reaching a 6.6-fold (p < 0.01) higher level by 60 weeks than in control ICR mice. Renal ET-3 mRNA levels, however, remained unchanged. The renal mRNA levels of ET receptor A and B in ddY mice increased gradually with the progression of nephritis, reaching 4.8- (p < 0.01) and 3.6-fold (p < 0.01) higher levels, respectively, at 60 weeks of age than found in control ICR mice. A positive correlation was noted between ET-1 and ET receptor mRNA levels and histopathological changes in renal tissues. In addition, we assessed whether a specific ET receptor A antagonist, FR 139317, affects the progression of glomerulonephritis in ddY mice. At 24 weeks of age (before glomerulonephritis developed), ddY mice were divided into two groups that received intraperitoneally either FR139317 or its vehicle (saline) daily for 36 weeks. The development of histopathological lesions and urinary protein excretion were suppressed by FR139317 treatment. These data suggest that ET families play a role in the progression of glomerulonephritis and that FR139317 treatment can be used therapeutically in ddY mice with IgA nephropathy.

Age Factors↗
PubMed1996

Modulation of endothelin family gene expression in renal hypertrophy.

The present study was designed to assess how the renal expression of mRNA for endothelin (ET) families is regulated during compensatory renal hypertrophy in rats. ET family gene expression was studied in the contralateral kidney of uninephrectomized and sham-operated rats. Rats were sacrificed at 0, 1, 3, 6, 12, adn 24 h after unilateral nephrectomy of the sham operation. Three hours after the left nephrectomy, ET-1 and ET receptor B mRNA levels in the renal cortex increased significantly (ET-1, 10.6-fold compared to those in sham-operated rats, p < 0.001, and ET receptor B, 6.8-fold, p < 0.001), and then decreased gradually to the control level after 24 h; in contrast, ET-3 and ET receptor A mRNA levels demonstrated little change throughout the experiment. We additionally measured the plasma ET concentration and renal ET-1 production following unilateral nephrectomy. ET-1 levels in the renal cortex increased gradually, with a peak 6 h after nephrectomy (3.6-fold compared to those in sham-operated rats, p < 0.01), and then decreased to the control level after 24 h. However, plasma ET-1 levels demonstrated little change until after 24 h. The glomerular expression of ET-1 and ET receptors A and B mRNA demonstrated minimal change throughout the experimental period. Glomerular ET-3 mRNA expression were detected in neither the unilateral nephrectomy nor the sham-operated rats. Our results indicate that the time course of the mRNA expression of ET-1 and ET receptor B differs from that of ET-3 and ET receptor A in the renal cortex, and that glomerular mRNA levels for ET families are not associated with renal hypertrophy in the early stages following unilateral nephrectomy.

Animals↗
PubMed1996

Effects of the PGI2 analog beraprost sodium on glomerular prostanoid synthesis in rats with streptozotocin-induced diabetes.

A study of albuminuria, creatinine clearance (CCr) and blood pressure of streptozotocin (STZ)-induced diabetic rats with or without treatment by a prostacyclin (PGI2) analog, beraprost sodium (BPS), is described. Glomerular prostanoid synthesis was measured by gas chromatography (GC) mass spectrometry. Renal specimens stained with hematoxylin and eosin and periodic acid-Schiff were examined by light microscopy. Mean values of albuminuria in BPS-treated diabetic rats were significantly decreased compared with those in nontreated diabetic rats. The ratio of kidney to body weight in the BPS-treated diabetic rats was significantly lower than that in the nontreated diabetic rats. Levels of CCr and blood pressure were decreased in diabetic rats after the treatment with BPS. GC mass spectrometry showed that BPS did not influence the glomerular synthesis of PGI2 and TXB2. No histologic injury in the renal tissues was observed in the diabetic rats with or without BPS treatment. We concluded that BPS (PGI2 analog) might decrease the levels of urinary albumin excretion and CCr due to its vasodilating effects in the early phase of STZ-induced diabetes in rats.

Albuminuria↗
PubMed1996

VEGF and flt. Expression time kinetics in rat brain infarct.

BACKGROUND AND PURPOSE: Vascular endothelial growth/vascular permeability factor (VEGF) is a candidate for an angiogenic and hyperpermeability inducing factor in an infarct because it is a secretable mitogen specific for endothelial cells and is upregulated by hypoxia. Our study attempts to clarify the chronological expression of VEGF and its receptor (flt) system in experimental cerebral infarction. METHODS: With the use of a reproducible middle cerebral artery occlusion model in rats, VEGF expression was identified by Western blotting with anti-VEGF antibody. The chronological expression of the VEGF/flt system was analyzed semiquantitatively by immunohistochemical means in infarcts with different time courses from 3 hours to 3 weeks. RESULTS: VEGF and flt were expressed exclusively in the ischemic brain. The bands obtained on the immunoblot at 38 and 45 kD are related to those of VEGF121 and VEGF165 isoforms. Macrophages, neurons, and glial cells chronologically expressed VEGF immunoreactivity in a different fashion. Both VEGF (bound) and flt were detected in endothelial cells along with the development of angiogenesis. CONCLUSIONS: In the ischemic brain the macrophages, neurons, and glial cells appear to contain VEGF. The VEGF receptor flt was induced in endothelial cells along with the progression of angiogenesis in infarct. The VEGF/flt system is thus considered to be involved in the healing process of brain infarct.

Animals↗
PubMed1996

Prostaglandin F synthase is localized to contractile interstitial cells in bovine lung.

It was recently found that certain cells in the alveolar septum of the bovine lung are enriched in prostaglandin F (PGF) synthase. In this study we used immunohistochemical techniques at both light and electron microscopic levels to further characterize the PGF synthase-positive cells. By double immunofluorescence staining of bovine lung cryostat sections, the alveolar septal cells labeled by anti-PGF synthase antibody were also intensely labeled for cytoplasmic actin but not for alpha-smooth muscle actin. This labeling pattern suggests that the PGF synthase-positive cells in the septum are "contractile interstitial cells," which resemble conventional fibroblasts but characteristically contain prominent bundles of actin filaments. Immunogold electron microscopy of ultra-thin frozen sections of bovine lung showed that alveolar interstitial cells extending long cytoplasmic processes and closely associated with alveolar capillaries were intensely labeled for PGF synthase. Capillary endothelial cells, alveolar epithelial cells, and some fibroblastic cells were devoid of labeling. On the basis of these findings, we conclude that PGF synthase is specifically expressed in contractile interstitial cells within the alveolar septum. The protein may be a useful marker for contractile interstitial cells, whose physiological function and role in various pathological conditions have not been characterized in detail.

Animals↗
PubMed1996

Advantages and disadvantages of dobutamine stress echocardiography compared with treadmill exercise electrocardiography in detecting ischemia.

We compared the effectiveness and practicability of dobutamine stress echocardiography (DSE) and treadmill exercise electrocardiographic testing (TMT) for detecting coronary artery disease. Ninety-six patients (mean age 58.8 +/- 9.0 years) who presented for coronary angiography underwent both DSE and symptom-limited TMT. Two-dimensional echocardiography was performed to detect ischemia-induced wall motion abnormalities during incremental dobutamine infusion (5-40 micrograms/kg per min administered in 5 min steps). The sensitivity of detecting ischemia was 63% for TMT and 79% for DSE (p < 0.05); the specificity was 61% for TMT and 88% for DSE (p < 0.05). The accuracy of TMT was 63% and of DSE 82% (p < 0.01). In patients in whom both tests gave true-positive results, the maximum ST depression was evaluated during DSE and TMT (n = 31). The ST segment depressions detected by DSE were significantly smaller than those detected by TMT (0.04 +/- 0.04 mV vs 0.17 +/- 0.07 mV, p < 0.01), and 10 patients had no evidence of ST segment depression despite the presence of new wall motion abnormalities. DSE took significantly longer to perform than TMT (26.0 +/- 5.0 min vs 5.5 +/- 2.0 min, p < 0.01). Thus, DSE is more sensitive, specific and accurate than TMT in detecting coronary artery disease and can detect ischemia at an earlier stage. However, it takes longer to perform than TMT and thus may be less suitable for routine clinical use.

Adult↗
PubMed1996

Studies of temporomandibular joint sounds; Part 4. Phase relations of TMJ sounds and jaw movement.

A study was conducted to investigate the timing relationship of temporomandibular joint (TMJ) sounds during mandibular movement, as evaluated by the location of the condyle, in relation to the articular fossa using axiograph recording. TMJ sounds during jaw opening and closing occurred over a wide range: opening sounds were observed within a range of 41-100% of maximum opening, while closing sounds occurred within 1-80% of maximum opening. In calculating the peak frequency of the joint sounds, it was noted that there was no correlation between the timing of the sound and its peak frequency. This study revealed that the acoustic characteristics of TMJ sounds may be unaffected by the location of the condyle.

Auscultation↗