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T Terasaki

Publications and source records attributed to T Terasaki.

At least 37 records · Page 2Linked to original sources
PubMed2000

Conditionally immortalized brain capillary endothelial cell lines established from a transgenic mouse harboring temperature-sensitive simian virus 40 large T-antigen gene.

Five immortalized brain capillary endothelial cell lines (TM-BBB1-5) were established from 3 transgenic mice harboring temperature-sensitive simian virus 40 large T-antigen gene (Tg mouse). These cell lines expressed active large T-antigen and grew well at 33 degrees C with a doubling time of about 20 to 30 hours. TM-BBBs also grew at 37 degrees C but not at 39 degrees C. However, growth was restored when the temperature of the culture was lowered to 33 degrees C. Although significant amounts of large T-antigen were shown to be present in the cell culture at 33 degrees C, there was less of this complex at 37 degrees C and 39 degrees C. TM-BBBs expressed the typical endothelial marker, von Willebrand factor, and exhibited acetylated low-density lipoprotein uptake activity. The alkaline phosphatase and gamma-glutamyltranspeptidase activity in TM-BBBs were -10% and 50% to 80% of brain capillary fraction of normal mice, respectively. D-mannitol transport in the both apical-to-basal and basal-to-apical directions across the TM-BBB was 2-fold greater than for inulin. TM-BBBs were found to express GLUT-1 but not GLUT-3, and exhibited concentration-dependent 3-O-methyl-D-glucose (3-OMG) uptake activity with a Michaelis-Menten constant of 6.59 +/- 1.16 mmol/l. Moreover, P-glycoprotein (P-gp) with a molecular weight of -170 kDa was expressed in all TM-BBBs. Both mdr1a and mdr1b mRNA were detected in TM-BBB4 using reverse transcription-polymerase chain reaction (RT-PCR) analysis. [3H]-Cyclosporin A uptake by TM-BBB was significantly increased in the presence of 100 micromol/l verapamil and vincristine, suggesting that TM-BBB exhibits efflux transport activity via P-gp. In conclusion, conditional brain capillary endothelial cell lines were established from Tg mice. This cell line expresses endothelial markers and transporters at the BBB and is able to regulate cell growth, due to the amount of active large T-antigen in the cell, by changing the culture temperature.

3-O-Methylglucose↗
PubMed2000

In-vivo and in-vitro evidence of a carrier-mediated efflux transport system for oestrone-3-sulphate across the blood-cerebrospinal fluid barrier.

The efflux transport of oestrone-3-sulphate, a steroid hormone sulphate, across the blood-cerebrospinal fluid barrier has been examined following its intracerebroventricular administration. [3H]Oestrone-3-sulphate was eliminated from cerebrospinal fluid (CSF) with an apparent efflux clearance of 205 microL min(-1) per rat. There was 25% of unmetabolized [3H]oestrone-3-sulphate in the plasma 5 min after intracerebroventricular administration, indicating that at least a part of [3H]oestrone-3-sulphate is transported from CSF to the circulating blood across the blood-CSF barrier. This efflux transport was inhibited by co-administration of excess oestrone-3-sulphate (25 mM 10 microL = 0.25 micromol) into rat cerebral ventricle. To characterize the oestrone-3-sulphate transport process, an in-vitro uptake experiment was performed using isolated rat choroid plexus. Oestrone-3-sulphate uptake by isolated rat choroid plexus was found to be a saturable process with a Michaelis-Menten constant (Km) of 18.1 +/- 6.3 microM, and a maximum uptake rate (Vmax) of 48.0 +/- 15.1 pmol min(-1) microL(-1) of tissue. The oestrone-3-sulphate transport process was temperature dependent and was inhibited by metabolic inhibitors such as 2,4-dinitrophenol and rotenone, suggesting an energy dependence. This uptake process was also inhibited by steroid hormone sulphates (1 mM dehydroepiandrosterone sulphate and 1 mM oestrone sulphate), bile acids (1 mM taurocholic acid and 1 mM cholic acid) and organic anions (1 mM sulphobromophthalein and 1 mM phenolsulphonphthalein), whereas 1 mM p-aminohippuric acid, 1 mM p-nitrophenol sulphate, 0.1 mM methotrexate and the cardiac glycoside, 2.5 microM digoxin, had little effect. In conclusion, these results provide evidence that oestrone-3-sulphate is transported from CSF to the circulating blood across the blood-CSF barrier via a carrier-mediated efflux transport system.

2,4-Dinitrophenol↗
PubMed2000

mRna expression and transport characterization of conditionally immortalized rat brain capillary endothelial cell lines; a new in vitro BBB model for drug targeting.

Brain capillary endothelial cell lines (TR-BBB) were established from a recently developed transgenic rat harboring temperature-sensitive simian virus 40 (ts SV 40) large T-antigen gene (Tg rat) and used to characterize the endothelial marker, transport activity, and mRNA expression of transporters and tight-junction strand proteins at the blood-brain barrier (BBB). These cell lines expressed active large T-antigen and grew well at 33 degrees C with a doubling-time of about 22-31 hr, but did not grow at 39 degrees C. TR-BBBs expressed the typical endothelial marker, von Willebrand factor, and exhibited acetylated low-density lipoprotein uptake activity. Although the gamma-glutamyltranspeptidase activity in TR-BBBs was approximately 13% of that of the brain capillary fraction of a normal rat, it was localized in the apical side, suggesting that it reflects the functional polarity of the in vivo BBB. The mRNA of tight-junction strand proteins such as claudine-5, occludin, and junctional adhesion molecule are expressed in TR-BBB13. Drug efflux transporter, P-glycoprotein, with a molecular weight of 170 kDa was expressed in all TR-BBBs and mdr 1a, mdr 1b, and mdr 2 mRNA were detected in TR-BBBs using RT-PCR. Moreover, mrp1 mRNA was expressed in all TR-BBBs. Influx transporter, GLUT-1, expressed at 55 kDa was revealed by Western blot analysis. It had 3-O-methyl-D-glucose (3-OMG) uptake activity which was concentration-dependent with a Michaelis-Menten constant of 9.86 +/- 1.20 mM. The mRNA of large neutral amino acid transporter, which consists of LAT-1 and 4F2hc was expressed in TR-BBBs. In conclusion, the conditionally immortalized rat brain capillary endothelial cell lines (TR-BBB) had endothelial makers, expressed mRNA for tight-junction strand proteins and the influx and efflux transporters and produced GLUT-1, which is capable of 3-OMG transport activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

[Chronic encapsulated intracerebral hematoma in thalamus with incongruous right homonymous hemianopia: a case report].

We presented a patient with chronic encapsulated intracerebral hematoma. This 49-year-old woman suffered from visual disturbance, and slowly progressive right hemiparesis, sensory disturbance of the right extremities and incongruous right homonymous hemianopia over 2 months. Computed tomography scanning showed high density area and ring enhancement, and magnetic resonance imaging revealed mixed intensity on T1 and T2-weighted images in her left thalamus and internal capsule. Angiographic studies revealed no vascular anomaly or tumor stain. The pathologic pictures indicated well-encapsulated hematoma containing fresh and old hematomas in the left thalamus. Most reported cases of this disease had hematomas in the subcortex and no cases had similar visual disturbance. This report was prepared because this condition is uncommon and may remain unrecognized.

Cerebral Hemorrhage↗
PubMed2000

[Carotid artery disease in patients with retinal vein and artery occlusion].

To evaluate carotid artery disease in patients with retinal vein occlusion (RVO) and with retinal artery occlusion (RAO), 41 RVO patients (male 21, female 20, mean age 63 +/- 12 years) and 59 RAO patients (male 39, female 20, mean age 66 +/- 12 years) were investigated. All patients were examined neurologically and underwent carotid ultrasound examination. Using carotid ultrasound, carotid artery disease was evaluated in terms of presence of plaque, echogenicity of the plaque, degree of stenosis, or presence of ulceration. Carotid plaque or occlusion of the carotid artery was observed more frequently in RAO patients than in RVO patients (ipsilateral side: p < 0.01, contralateral side: p < 0.001; Fisher's exact test). Heterogeneous plaque was found more frequently in RAO patients compared to RVO patients (ipsilateral side: p < 0.01, contralateral side: p < 0.02; Fisher's exact test). Ulcerated plaque was found only in patients with RAO. In conclusion, carotid artery disease was more frequently found in patients with RAO than in patients with RVO.

Aged↗
PubMed2000

[Cerebral embolism in systemic lupus erythematosus with Libman-Sacks endocarditis: a case report].

We presented a patient of cerebral embolism caused by Libman-Sacks endocarditis with systemic lupus erythematosus (SLE). This 35-year-old housewife with SLE suffered from abrupt visual disturbance in December 1998. Angiography revealed the occlusion of her right posterior cerebral artery. Transesophageal echocardiography showed the mitral regurgitation and hyperplasia of the anterior mitral valve leaflet without vegetation. In April 1999, she again suffered from sudden onset of transient left hemiparesis and dysphasia. Angiographic findings were unchanged. Transesophageal echocardiographic examination detected vegetation on the anterior mitral valve leaflet and aggravation of the mitral regurgitation. Laboratory examination revealed inactivity of SLE. No bacteria was recovered from repeated blood cultures. We diagnosed that Libman-Sacks vegetation caused cerebral embolism.

Adult↗
PubMed2000

[A case of Ondine curse associated with a medullary tumor].

A 49-year-old woman with 6 months history of body weight loss, muscle weakness, and dysarthria, was found with respiratory arrest and resuscitated in the morning of January 1999. An MRI brain scan revealed diffuse swelling and T2/FLAIR high signal intensity with mild Gadolinium enhancement in the lower pons and medulla oblongata. Although the histological diagnosis could not be obtained, glioma (astrocytoma) was suspected. In the morning of July 3rd she presented sweating and cyanosis. Her arterial oxygen saturation was 18%. When we asked her to breathe more, she kept breathing and oxygen saturation was normalized. However, she could not breathe at all when she fell asleep without stimulation. She was kept under respiratory support for 2 months. Her symptoms improved with fluctuating course after 70 Gy of radiation therapy. Ondine curse is one type of sleep apnea syndrome, defined as the selective disturbance of autonomous breathing. Surgical operation and stroke are the reported causes of this syndrome. Brainstem tumor is relatively common cause for children's Ondine curse. On the other hand, it rarely causes adult's Ondine curse as a main symptom.

Astrocytoma↗
PubMed1999

The blood-brain barrier efflux transporters as a detoxifying system for the brain.

The role played by efflux transport systems across the blood-brain barrier (BBB) in the disposition of xenobiotics in the brain is described. Several drugs and organic anions are transported across the BBB via P-glycoprotein and other carrier-mediated efflux transport systems. Studies using in vitro cultured brain capillary endothelial cells, kinetic analysis, and mdr1a gene knock-out mice have shown that P-glycoprotein, located on the BBB, restricts the entry of vincristine and quinidine to the brain. Brain microdialysis studies have demonstrated that the brain interstitial fluid (ISF) concentrations of quinolone antibiotics are significantly lower than their corresponding unbound serum concentrations. A distributed model analysis supports the finding that efflux transport systems on the BBB restrict distribution of 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxyinosine (DDI), and quinolone antibiotics. A brain efflux index (BEI) method has been developed to provide direct evidence of an efflux transport system for carrying substrates from the cerebrum to the circulating blood across the BBB. The BEI method revealed the existence of carrier-mediated efflux organic anion transport systems for compounds such as p-aminohippuric acid, AZT, DDI, taurocholic acid, BQ-123, and estron sulfate. Moreover, cerebral neurotransmitters such as gamma-aminobutyric acid, L-glutamic acid, and L-aspartic acid are transported from brain to the circulating blood in the intact form via a carrier-mediated efflux transport system. The BBB not only restricts nonspecific permeation from the circulating blood to the brain, but also functions as an active efflux transport system for xenobiotics. Accordingly, the BBB plays a very important role by pumping xenobiotics and some endogenous compounds out of the brain, acting as a central nervous system (CNS)-specific detoxifying system supporting and maintaining normal cerebral function.

Journal Article↗
PubMed1999

Differences in the hepatobiliary transport of two quinolone antibiotics, grepafloxacin and lomefloxacin, in the rat.

The biliary excretion of grepafloxacin (GPFX) was compared with that of lomefloxacin (LFLX) in rats. The biliary clearances (Cl(plasma)(bile)) of GPFX was 2.9 times greater than LFLX based on the plasma concentration reached during constant intravenous (i.v.) infusion. The liver-plasma unbound concentration ratio, K(pu), of GPFX (1.7) was also higher than that of LFLX (0.7). The hepatic uptake clearance, assessed from an integration plot analysis, of GPFX was comparable with the hepatic blood flow rate, and 1.5 times that of LFLX, indicating that membrane transport in the uptake process is more efficient for GPFX. This was also supported by the difference between the uptake clearance of GPFX and LFLX in isolated rat hepatocytes. The bile-liver unbound concentration ratio of GPFX and LFLX was approximately 6 and 3, respectively, and the biliary clearance based on the unbound liver concentration of GPFX was 1.8 times that of LFLX. These results suggest that the concentrative transport of GPFX also across the canalicular membrane was more efficient than that of LFLX. Thus, the membrane transport activity via both sinusoidal and canalicular membranes determines the net excretion of each compound.

Animals↗
PubMed1999

Effects of arginine-vasopressin fragment 4-9 on rodent cholinergic systems.

Arginine-vasopressin fragment 4-9 (AVP4-9) has been demonstrated in animal studies to facilitate learning and memory. To clarify the mechanisms of this facilitation, we focused on the effects of AVP4-9 on rodent cholinergic systems. AVP4-9 (0.1 microM) enhanced the basal and the high-potassium-evoked acetylcholine (ACh) release from rat hippocampal slices (122.4 and 120.0% of control, respectively) in the presence of 1.3 mM calcium (physiological level) at 60 min after the incubation at 37 degrees C. The AVP4-9-stimulated basal ACh release was inhibited by a V1-selective antagonist ([(beta-mercapto-beta,beta-cyclopentamethylene propionic acid)1, O-methyl-Tyr2, Arg8] vasopressin), but not by a V2-selective antagonist ([adamantaneacetyl1, O-ethyl-D-Tyr2, Val4, aminobutyryl6, Arg8,9]-vasopressin). In addition, AVP4-9 did not affect the basal ACh release under the calcium-free condition at 37 degrees C or in the presence of 1.3 mM calcium at 4 degrees C. However, AVP4-9 facilitated the passive-avoidance response of scopolamine (a cholinergic blocker)-induced memory-deficient mice. These findings demonstrate that AVP4-9 stimulates ACh release via mediation by V1-like vasopressin receptors, and shows dependence on calcium ion and temperature. The results also suggest that the mechanism of the facilitative effects of AVP4-9 on learning and memory consist of the observed stimulation of cholinergic systems and other parallel pathways that would not be inhibited by cholinergic blocking.

Acetylcholine↗
PubMed1999

Blood-brain barrier produces significant efflux of L-aspartic acid but not D-aspartic acid: in vivo evidence using the brain efflux index method.

The brain efflux index method has been used to clarify the mechanism of efflux transport of acidic amino acids such as L-aspartic acid (L-Asp), L-glutamic acid (L-Glu), and D-aspartic acid (D-Asp) across the blood-brain barrier (BBB). About 85% of L-[3H]Asp and 40% of L-[3H]Glu was eliminated from the ipsilateral cerebrum within, respectively, 10 and 20 min of microinjection into the brain. The efflux rate constant of L-[3H]Asp and L-[3H]Glu was 0.207 and 0.0346 min(-1), respectively. However, D-[3H]Asp was not eliminated from brain over a 20-min period. The efflux of L-[3H]Asp and L-[3H]Glu was inhibited in the presence of excess unlabeled L-Asp and L-Glu, whereas D-Asp did not inhibit either form of efflux transport. Aspartic acid efflux across the BBB appears to be stereospecific. Using a combination of TLC and the bioimaging analysis, attempts were made to detect the metabolites of L-[3H]Asp and L-[3H]Glu in the ipsilateral cerebrum and jugular vein plasma following a microinjection into parietal cortex, area 2. Significant amounts of intact L-[3H]Asp and L-[3H]Glu were found in all samples examined, including jugular vein plasma, providing direct evidence that at least a part of the L-Asp and L-Glu in the brain interstitial fluid is transported across the BBB in the intact form. To compare the transport of acidic amino acids using brain parenchymal cells, brain slice uptake studies were performed. Although the slice-to-medium ratio of D-[3H]Asp was the highest, followed by L-[3H]Glu and L-[3H]Asp, the initial uptake rate did not differ for both L-[3H]Asp and D-[3H]Asp, suggesting that the uptake of aspartic acid in brain parenchymal cells is not stereospecific. These results provide evidence that the BBB may act as an efflux pump for L-Asp and L-Glu to reduce the brain interstitial fluid concentration and act as a static wall for D-Asp.

Algorithms↗
PubMed1999

A novel stromal cell-dependent B lymphoid stem-like cell line that induces immunoglobulin gene rearrangement.

A stroma-dependent B lymphoid cell line (B31-1) has been established by coculturing sorted stem cells on a novel bone marrow stromal cell line (TBR31-1). B31-1 cells express B220, but do not express other B lymphoid differentiation markers including CD43, heat stable antigen (HSA), or surface immunoglobulin (Ig) M (sIgM), and their Ig heavy chain (IgH) gene loci are germ-line in configuration. The addition of interleukin (IL)-7 or coculture with another stromal cell line, ST2, induces D-J rearrangement of the IgH gene and B lymphocyte differentiation markers. B31-1 cells restore an in vivo repopulation activity to lethally irradiated mice, and the repopulated cells differentiate to HSA+ pre-B cells.Continuous coculture results in two distinct populations, B220(-) c-Kit+ cells and B220(+) c-Kit+ cells; B220(-) c-Kit+ cells are self-renewed and differentiate to B220(+) c-Kit+ cells, while B220(+) c-Kit+ cells produce only B220(+) c-Kit+ cells. Both B220(-) and B220(+) cells similarly express the IgH germ-line transcript (Imu), mRNAs for recombinase (TdT, Rag-1, and Rag-2), and lymphoid-specific transcription factors (Pax-5, EBF, E12/E47, Oct-2, and Ikaros), but the DNA binding activity of Pax-5, EBF, Oct-2, and E2A are low in B220(-) cells and while high in B220(+) cells. These results suggest the existence of at least two active states in the IgH locus before the induction of IgH gene rearrangement during B lymphopoietic development.

Animals↗
PubMed1999

[The significance of duplex ultrasonography examination in the acute cardioembolic stroke patients--with special attention to evaluation of internal carotid arteries].

The aim of this study is to clarify whether it is possible to diagnose occlusions of internal carotid arteries in the acute cardioembolic stroke patients by observing internal carotid arteries with duplex ultrasonography. Twenty-two consecutive patients underwent both duplex ultrasonography examination and cerebral angiography within 24 hours from the onset. Two cases who had no flow velocity and 8 cases who had systolic flow velocity but no anterograde diastolic flow velocity were all diagnosed as having internal carotid occlusions by cerebral angiography. Eleven of 22 cases who had anterograde diastolic flow velocity were diagnosed as having occlusions at distal side of M 1 portion or no occluded lesions. Besides, among 11 cases who were diagnosed as having occlusions of internal carotid arteries by cerebral angiography, five had end diastolic ratios (ED ratio) of common carotid arteries that were less than 4.0s. It is useful to evaluate the existence of anterograde diastolic flow velocity by duplex ultrasonography for the diagnosis of internal carotid occlusions in the acute cardioembolic stroke patients.

Acute Disease↗
PubMed1999

In vivo and in vitro evidence of blood-brain barrier transport of a novel cationic arginine-vasopressin fragment 4-9 analog.

The blood-brain barrier (BBB) transport and metabolism of a novel arginine-vasopressin fragment 4-9 [AVP(4-9), isoelectric point; (pI) = 9.2] analog, that is, cationic AVP(4-9) (C-AVP(4-9), PI = 9.8), were examined in vivo and in vitro. At 45 min after an i.v. administration to mice, the cerebrum-to-plasma concentration ratios of (35)S-labeled AVP(4-9) and (125)I-labeled C-AVP(4-9) were 0.103 and 0.330 ml/g cerebrum, respectively, and the BBB permeation clearances were 1.47 x 10(-4) and 3.10 x 10(-4) ml/min/g cerebrum, respectively. In the in vitro study using mouse brain capillary endothelial cells immortalized by SV40 infection (MBEC4), the acid-resistant binding values of (35)S-labeled AVP(4-9) and (125)I-labeled C-AVP(4-9) to MBEC4 at 120 min were 0.93 and 1.95 microliter/mg protein (as the cell/medium ratios), respectively. (35)S-labeled AVP(4-9) showed two-phase saturable acid-resistant binding, and its half-saturation constants (K(D)) were 3.8 nM (high affinity) and 45.7 microM (low affinity). (125)I-labeled C-AVP(4-9) showed single-phase saturable acid-resistant binding, with a K(D) value of 16.4 microM. The acid-resistant binding of (125)I-labeled C-AVP(4-9) was significantly dependent on temperature and medium osmolarity. The acid-resistant binding of (125)I-labeled C-AVP(4-9) was inhibited by dancylcadaverine, phenylarsine oxide (endocytosis inhibitors), 2,4-dinitrophenol (a metabolic inhibitor), and AVP(4-9), poly(L-lysine), and protamine (cationic substances), but not by poly(L-glutamic acid) (an anionic peptide) and the V(1) and V(2) vasopressin receptor antagonists. In addition, the conversion of C-AVP(4-9) to AVP(4-9) in the cerebral homogenate was confirmed by HPLC and mass spectrometry. The present results demonstrate that C-AVP(4-9) is transported through the BBB more effectively than AVP(4-9), via absorptive-mediated endocytosis, and that C-AVP(4-9) is converted to the neuroactive parent peptide, AVP(4-9), in the cerebrum.

Animals↗
PubMed1999

[Two cases of brain infarction associated with dissection of the thoracic aorta].

Case 1: a 57-year-old woman, who suddenly developed disturbance of consciousness, left spatial neglect, and left hemiparesis, was admitted to our hospital on the day 1. Brain CT scan on the day 2 revealed broad edematous infarction in her middle cerebral artery territory. The dissection of the thoracic aorta was observed with transesophageal echocardiography and brain embolism due to mural thrombus of the dissecting thoracic aorta was suspected. Case 2: a 67-year-old woman, who developed disturbance of consciousness, left spatial neglect, and left hemiparesis, was admitted to our hospital on the day 15. Brain CT scan on the day 15 showed non-edematous infarction in her middle cerebral artery territory. Contrast thoracic CT scan on the day 31 revealed the dissection of the thoracic aorta. No clinical exacerbation was observed, but brain CT scan on the day 94 showed broad infarction in her middle and anterior cerebral artery territories. It is considered that pseudolumen of the dissected thoracic aorta caused occlusion of her right internal carotid artery. Transesophageal echocardiography, or contrast thoracic CT scan should be considered for detection of the dissection of the thoracic aorta in the cases of cryptogenic stroke.

Aged↗
PubMed1999

[Cerebral infarction associated with mobile thoracic ascending aortic thrombus in a patient with essential thrombocythemia].

A 77-year-old man with essential thrombocythemia had embolic stroke associated with mobile thoracic ascending aortic thrombus despite of receiving antiplatelet drug. He had history of toe ulcer and ileus within previous 2 years. He was diagnosed as essential thrombocythemia and received antiplatelet drug. He had consciousness disturbance and admitted to our hospital. Cerebral angiography disclosed emboli in the right middle cerebral artery (M2). Transesophageal echocardiography showed evidence of a mobile thrombus attached to the wall of the ascending aorta at the first day. The thrombus was no longer present after treatment with heparin followed by no recurrent embolic event. We prescribed hydroxyurea for essential thrombocythemia for chronic phase treatment. We consider that with essential thrombocythemia the thrombus of the ascending aorta caused the cerebral infarction. And we succeeded of the treatment of the embolic stroke and prevalence of the emboli with essential thrombocythemia.

Aged↗
PubMed1999

[Neovascular glaucoma following cataract surgery--a case report].

A 75-year-old man suffered from right neovascular glaucoma following ipsilateral cataract surgery. Cerebral angiogram showed occlusion of the right internal carotid artery and the steal phenomenon of right ophthalmic artery. Chronic ocular ischemia caused by carotid occlusion and ophthalmic artery steal phenomenon is one of the decisive risk factors for secondary glaucoma after cataract surgery.

Aged↗