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Biomedical subjects

H Segawa

Publications and source records attributed to H Segawa.

At least 19 recordsLinked to original sources
PubMed2006

A third-generation bisphosphonate, minodronic acid (YM529), successfully prevented the growth of bladder cancer in vitro and in vivo.

Minodronic acid (YM529) is a third-generation bisphosphonate (BP) that has been shown to directly and indirectly prevent proliferation, induce apoptosis, and inhibit metastasis of various types of cancer cells. In this study, we have investigated the therapeutic efficacy of YM529 against bladder cancer, both in vitro and in vivo. YM529 inhibited geranylgeranylation as well as farnesylation and reduced the growth of all seven bladder cancer cell lines in a dose- and time-dependent manner in vitro. YM529 demonstrated a good synergistic or additive antiproliferative effect when administered in combination with cisplatin or paclitaxel. Immunohistochemical study revealed YM529 inhibited the prenylation of Rap1A in vivo. YM529 administered systemically did not markedly inhibit the growth of visceral metastases but it showed a significant anticancer effect on bone metastases monitored by an in vivo imaging system. Moreover, intravesical YM529 demonstrated significant growth inhibition in a bladder cancer orthotopic model. No adverse effects were associated with the systemic as well as the intravesical treatment regimens. In conclusion, our study suggests that YM529 may be a potent anticancer agent for bladder cancer. The efficacy and safety of this BP as an agent for combination chemotherapies against bladder cancer should be verified by early-phase clinical trials.

Animals↗
PubMed2006

Improved photocatalytic activity of zeolite- and silica-incorporated TiO2 film.

Porous TiO2 film was prepared by sol-gel method from TiO2 sol containing polyvinylpyrolidone (PVP). Photocatalytic activity of the film was evaluated by the elimination rate of ethylene. Several adsorbents including zeolite and silica powders were incorporated into the TiO2 film. All the adsorbents enhanced the activity. The optimum adsorbent content was 0.005-0.01 g/ml of the coating sol solution. Silica provided better activity than zeolite. At high humidity and in dry air the activity decreased.

Catalysis↗
PubMed2003

Cloning, gene structure and dietary regulation of the type-IIc Na/Pi cotransporter in the mouse kidney.

We have demonstrated previously that the type-IIc Na/Pi cotransporter is a growth-related renal Na/Pi cotransporter that is highly expressed in kidney of the weaning rat. In the present study, we investigated type-IIc Na/Pi cotransporter function further by cloning the mouse gene and characterizing the corresponding protein. The mouse type-IIc transporter amino acid sequence shows a high degree of similarity to the human (86%) and rat (95%) type-IIc Na/Pi-cotransporters. The mouse gene contained 14 exons and mapped to chromosome 2. The DNA sequence upstream from exon 1 is GC rich. The upstream region does not contain an apparent TATA box, but does contain two dietary Pi-responsive elements, which are potential binding sites for the transcription factor micro E3 (TFE3). Microinjection of mouse type-IIc cRNA into Xenopus oocytes demonstrated sodium-dependent Pi cotransport activity. The affinity for Pi was about 200 microM in 100 mM Na. Feeding adult mice fed a low-Pi diet increased the expression of type-IIc protein in the apical membrane of renal proximal tubular cells. Hybrid depletion studies suggested that the type-IIc transporter contributes to about 30% of Na/Pi cotransport in the kidney of adult mice fed a low-Pi diet. The present study suggests that the type-IIc Na/Pi cotransporter is a functional of renal Pi transporter in adult mice fed a low-Pi diet.

Amino Acid Sequence↗
PubMed2002

Effects of propofol on lactate accumulation and oedema formation in focal cerebral ischaemia in hyperglycaemic rats.

BACKGROUND: In cerebral ischaemia, hyperglycaemia brings about severe lactate accumulation and neuronal damage when compared with normoglycaemia. Propofol has been known to suppress glucose metabolism in the brain and possess neuroprotective properties in cerebral ischaemia. Therefore, in this study we examined if propofol could attenuate lactate accumulation and neuronal damage in cerebral ischaemia under hyperglycaemic conditions. METHODS: Ten male wistar rats were divided into two experimental groups: low-dose (approximately 12 mg kg(-1) h(-1)) and high-dose (approximately 60 mg kg(-1) h(-1)) propofol groups (n=5 for each). Following injection of 2 g kg(-1) glucose intraperitoneally, the middle cerebral artery was occluded for 1 h, and then reperfused for the following 2 h. Lactate accumulation and oedema formation were estimated consecutively using nuclear magnetic resonance (NMR) techniques. RESULTS: Lactate accumulation and oedema formation increased continuously during ischaemia and reperfusion in the low-dose propofol group, which was attenuated in the high-dose propofol group. Lactate/NAA (N-acetylaspartate) ratio (as an index of lactate accumulation) 60 and 120 min after reperfusion were 2.67 and 3.26 in low-dose group and 0.30 and 0.10 in high-dose group. For NMR images the number of pixels with a low average diffusion coefficient (an index of the oedema formation), 60 and 120 min after reperfusion were 250.0 and 317.8 in low-dose group, and 16.0 and 12.4 in high-dose group. CONCLUSION: High-dose propofol attenuated lactate accumulation and oedema formation in cerebral ischaemia in hyperglycaemic rats.

Anesthetics, Intravenous↗
PubMed2002

Effects of xenon on acetylcholine release in the rat cerebral cortex in vivo.

BACKGROUND: We have reported previously the effects of several anaesthetics on cholinergic activity in the central nervous system (CNS). In this study, we report the effects of xenon on cholinergic cell activity. METHODS: Using in vivo brain microdialysis, we measured acetylcholine (ACh) release in the rat cerebral cortex in vivo during xenon anaesthesia. RESULTS: Xenon induced an initial increase in ACh release, followed by a gradual decrease. The level of Ach release at 40 min of xenon administration was significantly higher than the control. CONCLUSIONS: Xenon activates CNS cholinergic cell activity followed by development of acute tolerance.

Acetylcholine↗
PubMed2001

Modulation of event-related potentials in normal human subjects by visual divided attention to spatial and color factors.

We investigated how visual event-related potentials (ERPs) are modulated by visual divided attention using an S1-S2 paradigm. Stimulus S2 consisted of non-target stimuli (Stimulus 1, 2, 3) and a target stimulus (Stimulus 4). The spatial/color factor was compared between S1 and S2: same/same (Stimulus 1); same/different (Stimulus 2); different/same (Stimulus 3); and different/different (Stimulus 4). The P1/N1 (90 approximately 150 ms) showed significantly greater amplitude in Stimulus 3 than in Stimuli 1 and 2. The N2 (230 approximately 290ms) showed significantly greater amplitude in Stimulus 2 than in Stimuli 1 and 3. We assumed that the P1/N1 was related to spatial attention, enhanced by alterations to the spatial factor, and that the N2 was related to color attention, enhanced by alterations to the color factor.

Adult↗
PubMed2001

Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.

System L is a major nutrient transport system responsible for the transport of large neutral amino acids including several essential amino acids. We previously identified a transporter (L-type amino acid transporter 1: LAT1) subserving system L in C6 rat glioma cells and demonstrated that LAT1 requires 4F2 heavy chain (4F2hc) for its functional expression. Since its oncofetal expression was suggested in the rat liver, it has been proposed that LAT1 plays a critical role in cell growth and proliferation. In the present study, we have examined the function of human LAT1 (hLAT1) and its expression in human tissues and tumor cell lines. When expressed in Xenopus oocytes with human 4F2hc (h4F2hc), hLAT1 transports large neutral amino acids with high affinity (K(m)= approximately 15- approximately 50 microM) and L-glutamine and L-asparagine with low affinity (K(m)= approximately 1.5- approximately 2 mM). hLAT1 also transports D-amino acids such as D-leucine and D-phenylalanine. In addition, we show that hLAT1 accepts an amino acid-related anti-cancer agent melphalan. When loaded intracellularly, L-leucine and L-glutamine but not L-alanine are effluxed by extracellular substrates, confirming that hLAT1 mediates an amino acid exchange. hLAT1 mRNA is highly expressed in the human fetal liver, bone marrow, placenta, testis and brain. We have found that, while all the tumor cell lines examined express hLAT1 messages, the expression of h4F2hc is varied particularly in leukemia cell lines. In Western blot analysis, hLAT1 and h4F2hc have been confirmed to be linked to each other via a disulfide bond in T24 human bladder carcinoma cells. Finally, in in vitro translation, we show that hLAT1 is not a glycosylated protein even though an N-glycosylation site has been predicted in its extracellular loop, consistent with the property of the classical 4F2 light chain. The properties of the hLAT1/h4F2hc complex would support the roles of this transporter in providing cells with essential amino acids for cell growth and cellular responses, and in distributing amino acid-related compounds.

Amino Acid Transport Systems↗
PubMed2001

Molecular events involved in up-regulating human Na+-independent neutral amino acid transporter LAT1 during T-cell activation.

We investigated the regulation of system-L amino acid transporter (LAT1) during T-cell activation. In quiescent T-cells, L-leucine transport is mediated mainly by the system-L amino acid transport system and is increased significantly during T-cell activation by PMA and ionomycin. In quiescent T-cells, the LAT1 protein was heterocomplexed with 4F2 heavy chain (4F2hc) in the plasma membrane. During T-cell activation, the amounts of 4F2hc and LAT1 heterocomplex were significantly elevated compared with those in quiescent T-cells. In addition, by Northern-blot analysis, these increments were found to be due to elevated levels of LAT1 and 4F2hc mRNA. Transient expression of constructs comprising various LAT1 gene promoter fragments, which contained all three of the GC boxes, was sufficient for promoting luciferase expression in Jurkat T-cells, but the promoter of the LAT1 gene did not respond to PMA and ionomycin. Similar observations were observed in the human 4F2hc gene promoter. In nuclear run-on assay, the LAT1 and 4F2hc genes were actively transcribed even in quiescent T-cells, but the low levels of both transcripts were shown to be the result of a block to transcription elongation within the exon 1 intron 1 regions. These findings indicated that a removal of the block to mRNA elongation stimulates the induction of system-L amino acid transporter gene transcripts (LAT1 and 4F2hc) in activated T-cells.

Amino Acid Sequence↗
PubMed2001

Bone tunnel enlargement after anterior cruciate ligament reconstruction using hamstring tendons.

We retrospectively reviewed 87 anterior cruciate ligament reconstructions using autogenous hamstring tendons with the Endobutton technique to investigate the relationship between bone tunnel enlargement and clinical outcome and to identify factors that contribute to the enlargement. The clinical outcome was evaluated using the Lysholm score and KT-1000 arthrometer. The location of the femoral tunnel with respect to Blumensaat's line, the tibial tunnel with respect to the tibial plateau, and the angle between the femoral tunnel and Blumensaat's line (femoral tunnel angle) were measured. Bone tunnel enlargement was observed in 32 patients (37%). Enlargement occurred in 22 of the femoral tunnels and 26 of the tibial tunnels. Enlargement of both tunnels occurred in 16 knees. There was no statistical difference in Lysholm scores or KT-1000 arthrometer measurements between the enlarged group and the unenlarged group. The femoral tunnel was placed more anteriorly in the enlarged femoral tunnel group than in the unenlarged femoral tunnel group. The tibial tunnel was placed more anteriorly in the enlarged tibial tunnel group than in the unenlarged tibial tunnel group. The femoral tunnel angle was significantly smaller in the enlarged femoral tunnel group than in the femoral unenlarged group. Gender, patient age, intraoperative isometricity, and graft size were not significant factors. Bone tunnel enlargement was not correlated with the clinical outcome measures. We conclude that the main factor associated with tunnel enlargement are the locations and angles of the tunnels. The windshield-wiper motion of the graft may be enhanced by changing tension in the graft due to tunnel malposition. An acute femoral tunnel angle may increase the mechanical stress on the anterior margin of the femoral tunnel.

Adolescent↗
PubMed2001

Multiple osteochondroses of bilateral knee joints.

We experienced a patient with a combination of multiple osteochondroses: Blount's disease, bipartite patella, and Sinding-Larsen-Johansson disease in the left knee, and a combination of bipartite patella and Osgood-Schlatter disease in the right knee. The patient was a healthy, active 12-year-old boy with bilateral knee pain. He had been diagnosed with Blount's disease of the left tibia at 2 years of age, and had been treated with open wedge osteotomy. He was diagnosed with bilateral bipartite patellae at the age of 9 years, and was diagnosed with Osgood-Schlatter disease in the right knee and Sinding-Larsen-Johansson disease in the left knee at 10 years of age. The second growth spurt was observed during this period. At 11 years of age, he was diagnosed with an osteochondral fracture of the left lateral femoral condyle and was observed without surgery. This patient showed the sequential appearance of an ossification disorder, probably due to the abnormal response of enchondral ossification to mechanical stress. Overuse in this growth period may have played a role in the development of these osteochondroses. The osteochondral fracture was probably caused by a disruption at one of the weakest parts of the developing skeleton, between the ossification center and the overlying cartilage in the background of an ossification disorder.

Body Height↗
PubMed2001

Functional repression of Islet-2 by disruption of complex with Ldb impairs peripheral axonal outgrowth in embryonic zebrafish.

Islet-2 is a LIM/homeodomain-type transcription factor of the Islet-1 family expressed in embryonic zebrafish. Two Islet-2 molecules bind to the LIM domain binding protein (Ldb) dimers. Overexpression of the LIM domains of Islet-2 or the LIM-interacting domain of Ldb proteins prevented binding of Islet-2 to Ldb proteins in vitro and caused similar in vivo defects in positioning, peripheral axonal outgrowth, and neurotransmitter expression by the Islet-2-positive primary sensory and motor neurons as the defects induced by injection of Islet-2-specific antisense morpholino oligonucleotide. These and other experiments, i.e., mosaic analysis, coexpression of full-length Islet-2, and overexpression of the chimeric LIM domains derived from two different Islet-1 family members, demonstrated that Islet-2 regulates neuronal differentiation by forming a complex with Ldb dimers and possibly with some other Islet-2-specific cofactors.

Animals↗
PubMed2001

Long-term results of non-operative treatment of anterior cruciate ligament injury.

We retrospectively reviewed the record of 89 patients with complete anterior cruciate ligament injury, documented by arthroscopic examination to investigate the long-term results in relation to the generation of osteoarthritis. The mean age of the patients was 34.9 years at follow-up and the mean duration of follow-up was 12.0 years. The mean Lysholm score was 89 points at follow-up. The mean Tegner activity score was 5.7 points before injury and 4.5 points at follow-up. Plain radiographs revealed 63% of osteoarthritis and 37% of which had joint space narrowing. The age of the patients, the level of sports activity, the history of meniscectomy, obesity and the osteoarthritis of the contralateral knee were found to be significant risk factors in osteoarthritis after anterior cruciate ligament injury. The most influential factor for osteoarthritis was considered meniscectomy, in combination with the risk factors of primary osteoarthritis. It should also be noted that modification of sports activity level was the most important factor for avoiding the combined injury of meniscus and osteoarthritis.

Adult↗
PubMed2001

[Cellular mechanisms in proximal tubular handling of phosphate].

In the kidney, reabsorption of filtered inorganic phosphate (Pi) takes place along the proximal tubules and is controlled by a variety of hormones (e.g.parathyroid hormone, PTH). Three structurally unrelated sodium-dependent phosphate (Na/Pi) cotransporter families have been identified. Targeted inactivation of the type IIa Na/Pi cotransporter gene (npt2) provided strong evidence that - 70% of Na-dependent Pi transport across the brush border membrane is mediated by the type IIa Na/Pi cotransporter. The type IIa cotransporter represents the major target for PTH. The type IIa cotransporter interacts with various PDZ proteins that might be responsible for the apical sorting, PTH controlled endocytosis or the lysosomal sorting internalized type IIa cotransporter.

English Abstract↗
PubMed2000

Transport properties of a system y+L neutral and basic amino acid transporter. Insights into the mechanisms of substrate recognition.

The properties of system y(+)L-mediated transport were investigated on rat system y(+)L transporter, ry(+)LAT1, coexpressed with the heavy chain of cell surface antigen 4F2 in Xenopus oocytes. ry(+)LAT1-mediated transport of basic amino acids was Na(+)-independent, whereas that of neutral amino acids, although not completely, was dependent on Na(+), as is typical of system y(+)L-mediated transport. In the absence of Na(+), lowering of pH increased leucine transport, without affecting lysine transport. Therefore, it is proposed that H(+), besides Na(+) and Li(+), is capable of supporting neutral amino acid transport. Na(+) and H(+) augmented leucine transport by decreasing the apparent K(m) values, without affecting the V(max) values. We demonstrate that although ry(+)LAT1-mediated transport of [(14)C]l-leucine was accompanied by the cotransport of (22)Na(+), that of [(14)C]l-lysine was not. The Na(+) to leucine coupling ratio was determined to be 1:1 in the presence of high concentrations of Na(+). ry(+)LAT1-mediated leucine transport, but not lysine transport, induced intracellular acidification in Chinese hamster ovary cells coexpressing ry(+)LAT1 and 4F2 heavy chain in the absence of Na(+), but not in the presence of physiological concentrations of Na(+), indicating that cotransport of H(+) with leucine occurred in the absence of Na(+). Therefore, for the substrate recognition by ry(+)LAT1, the positive charge on basic amino acid side chains or that conferred by inorganic monovalent cations such as Na(+) and H(+), which are cotransported with neutral amino acids, is presumed to be required. We further demonstrate that ry(+)LAT1, due to its peculiar cation dependence, mediates a heteroexchange, wherein the influx of substrate amino acids is accompanied by the efflux of basic amino acids.

Amino Acid Transport Systems, Basic↗
PubMed2000

Identification and characterization of a Na(+)-independent neutral amino acid transporter that associates with the 4F2 heavy chain and exhibits substrate selectivity for small neutral D- and L-amino acids.

A cDNA was isolated from the mouse brain that encodes a novel Na(+)-independent neutral amino acid transporter. The encoded protein, designated as Asc-1 (asc-type amino acid transporter 1), was found to be structurally related to recently identified mammalian amino acid transporters for the transport systems L, y(+)L, x(C)(-), and b(0,+), which are linked, via a disulfide bond, to the type II membrane glycoproteins, 4F2 heavy chain (4F2hc), or rBAT (related to b(0,+) amino acid transporter). Asc-1 required 4F2hc for its functional expression. In Western blot analysis in the nonreducing condition, a 118-kDa band, which seems to correspond to the heterodimeric complex of Asc-1 and 4F2hc, was detected in the mouse brain. The band shifted to 33 kDa in the reducing condition, confirming that Asc-1 and 4F2hc are linked via a disulfide bond. Asc-1-mediated transport was not dependent on the presence of Na(+) or Cl(-). Although Asc-1 showed a high sequence homology (66% identity at the amino acid level) to the Na(+)-independent broad scope neutral amino acid transporter LAT2 (Segawa, H., Fukasawa, Y., Miyamoto, K., Takeda, E., Endou, H., and Kanai, Y. (1999) J. Biol. Chem. 274, 19745-19751), Asc-1 also exhibited distinctive substrate selectivity and transport properties. Asc-1 preferred small neutral amino acids such as Gly, L-Ala, L-Ser, L-Thr, and L-Cys, and alpha-aminoisobutyric acid as substrates. Asc-1 also transported D-isomers of the small neutral amino acids, in particular D-Ser, a putative endogenous modulator of N-methyl-D-aspartate-type glutamate receptors, with high affinity. Asc-1 operated preferentially, although not exclusively, in an exchange mode. Asc-1 mRNA was detected in the brain, lung, small intestine, and placenta. The functional properties of Asc-1 seem to be consistent with those of a transporter subserving the Na(+)-independent small neutral amino acid transport system asc.

Amino Acid Sequence↗
PubMed2000

Boomerang deformity of cervical spinal cord migrating between split laminae after laminoplasty.

Patients with cervical compression myelopathy were studied to elucidate the mechanism underlying boomerang deformity, which results from the migration of the cervical spinal cord between split laminae after laminoplasty with median splitting of the spinous processes (boomerang sign). Thirty-nine cases, comprising 25 patients with cervical spondylotic myelopathy, 8 patients with ossification of the posterior longitudinal ligament, and 6 patients with cervical disc herniation with developmental canal stenosis, were examined. The clinical and radiological findings were retrospectively compared between patients with (B group, 8 cases) and without (C group, 31 cases) boomerang sign. Moderate increase of the grade of this deformity resulted in no clinical recovery, although there was no difference in clinical recovery between the two groups. Most boomerang signs developed at the C4/5 and/or C5/6 level, where maximal posterior movement of the spinal cord was achieved. Widths between lateral hinges and between split laminae in the B group were smaller than in the C group. Flatness of the spinal cord in the B group was more severe than in the C group. In conclusion, the boomerang sign was caused by posterior movement of the spinal cord, narrower enlargement of the spinal canal and flatness of the spinal cord.

Adult↗
PubMed2000

Radiosurgery of meningeal melanocytoma.

The authors present a case of meningeal melanocytoma arising from Meckel's cave. A coal-black, vascular tumor was partially removed by surgery. Histopathologically, the tumor lacked anaplastic features. Immunohistochemical studies confirmed that the tumor was of neuroectodermal origin and had low proliferating activity. The patient underwent gamma knife radiosurgery for the residual tumor, in which 25 Gy of radiation was delivered to the tumor margin. Three years after irradiation, the tumor showed marked shrinkage without complication.

Adult↗