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Biomedical subjects

K Abe

Publications and source records attributed to K Abe.

At least 145 records · Page 8Linked to original sources

Determination of the subthreshold state contribution in 13C(alpha,n)16O, the main neutron-source reaction for the s process.

The reaction rate of the stellar reaction 13C(alpha,n)16O, which is currently considered to be the main neutron source for the slow (s) process at low energies, has been rederived using the direct alpha-transfer reaction 13C(6Li,d)17O leading to the subthreshold state at 6.356 MeV in 17O. The contribution of the subthreshold state is found to be much smaller than the currently accepted predictions for the main neutron source of the s process, indicating less of a role of this reaction as the neutron source for the s-process scenario in low-mass stars at the asymptotic giant branch.

Journal Article↗

Measurement of the electroweak penguin process B-->X(s)l+l-.

We report the first measurement of the branching fraction for the inclusive decay B-->X(s)l(+)l(-), where l is either an electron or a muon, and X(s) is a hadronic recoil system that contains an s quark. We analyzed a data sample of 65.4 x 10(6) B meson pairs collected with the Belle detector at the KEKB e(+)e(-) asymmetric-energy collider. We find B(B-->X(s)l(+)l(-))=[6.1 +/-1.4(stat) +1.4-1.1(syst)] x 10(-6) for dilepton masses greater than 0.2 GeV/c(2).

Journal Article↗

Highly polysialylated neural cell adhesion molecule (PSA-NCAM) positive cells are increased and change localization in rat hippocampus by exposure to repeated kindled seizures.

The highly polysialylated neural cell adhesion molecule (PSA-NCAM) is involved in migration of neural stem cells as well as in neural plasticity. Immunoreactive PSA-NCAM expression was examined in rats with repeated exposure to amygdaloid kindled generalized seizures (GS). The number of PSA-NCAM positive cells in the bilateral dentate gyrus (DG) increased significantly from GS. Although the total number of positive cells was not significantly different between animals with 3 times GS (3 GS) and 30 times GS (30 GS), in the latter group a greater number of positive cells was observed in the outer granule cell layer (GCL) and a marked extension of immunopositive dendrites to the molecular layer. These observations indicate that increased migration of newly generated cells as well as plastic changes of preexisting neural cells occur in response to recurrent GS. This may contribute to an abnormal reconstruction of the synaptic network in the hippocampus and, thus, epileptogenicity from kindling.

Animals↗

Changes of free cholesterol and neutral lipids after transient focal brain ischemia in rats.

We investigated temporal and spatial changes of free cholesterol (FC) and neutral lipids (NLs) after brain ischemia with filipin complex staining to detect mainly FC and Nile Red staining for NLs such as cholesteryl ester (CE) and triacylglyceride (TAG). Filipin stainining decreased during 1 to 7 d and lost at 21 d after transient middle cerebral artery (MCA) occlusion in the ischemic core, but did not change in the penumbra. Nile Red positive droplets reached the maximum at 7 d after transient MCA occlusion (MCAO) and gradually decreased in the core, while the peak time delayed in the penumbra. Most Nile Red positive droplets were double positive for ED1 in the core, and were localized within GFAP positive cells in the penumbra. The present study suggests that changes of FC and NLs are different temporally and spatially between the ischemic core and the penumbra in relation to degenerative and regenerative neural processes following brain ischemia. Macrophages and astrocytes are presumed to play important roles in lipid metabolism for neural reorganization of the ischemic brain injury in the ischemic core and the penumbra, respectively.

Animals↗

Dissociative increase of oligodendrocyte progenitor cells between young and aged rats after transient cerebral ischemia.

Oligodendrocyte progenitor cells (OPCs) mature to oligodendrocyte and remyelinate axons. OPCs express neuron-glial antigen 2 (NG2) chondroitin sulfate proteoglycan. We stained NG2 to investigate the effect of aging on the OPCs after cerebral ischemia. NG2 positive cells were examined at 1, 3, 7 days after 90 min of transient middle cerebral artery occlusion in young and aged brains. The number of NG2 positive cells increased in the ischemic penumbra at 3 and 7 days after reperfusion. At 7 day, the number of NG2 positive cells was significantly greater in the young than the aged brains, and the processes of NG2 positive cells enlarged and were more highly branched in the young than the aged brains. These results suggest that the young brain shows a higher potential of proliferation and process branching of OPCs than the aged brain.

Aging↗

Ameliorative effect of NC-1900, a new AVP4-9 analog, through vasopressin V1A receptor on scopolamine-induced impairments of spatial memory in the eight-arm radial maze.

The mechanism by which NC-1900, a new pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH(2) (AVP(4-9)) analog, improves spatial memory in rats using an eight-arm radial maze was examined. Even at very low doses (0.2 ng/kg for s.c., 1 microg/kg for p.o., 1 fg for i.c.v.) NC-1900 improved scopolamine-induced impairment of spatial memory. NC-1900 (1 ng/kg, s.c.) also improved impairment of spatial memory induced by pirenzepine, a muscarinic(1) (M(1)) receptor antagonist, and by KN-62, a Ca2+/calmodulin (CaM)-dependent protein kinase II inhibitor. [Pmp(1), Tyr(Me)(2)]-Arg(8)-vasopressin, a vasopressin(1A) (V(1A)) receptor antagonist, and nicardipine, L-type Ca2+ blocker, but not OPC-31260, a V(2) antagonist, suppressed the effect of NC-1900 on scopolamine-induced impairment of spatial memory. A microdialysis study showed that NC-1900 did not affect acetylcholine release in the ventral hippocampus (VH) of intact rats or of scopolamine-treated rats. NC-1900 (1 microM) increased [Ca2+](i) in the VH than in the dorsal hippocampus (DH). Pretreatment with nicardipine (1 microM) and Ca2+ -free conditions inhibited the NC-1900-induced [Ca2+](i) response in the VH. Whereas co-administration of NC-1900 (1 microM) and carbachol (500 microM) increased [Ca2+](i) in the VH. Moreover, nicardipine concentration-dependently inhibited the increase in [Ca2+](i) induced by the co-administration of NC-1900 and carbachol in the VH. These results suggest that NC-1900 activates the V(1A) receptor at the postsynaptic cholinergic nerve, and causes a transient influx of intracellular Ca2+ through L-type Ca2+ channels, to interact with the M(1) receptor. The activation of these Ca2+ -dependent processes induced by NC-1900 may be involved in the positive effect of NC-1900 on scopolamine-induced impairment of spatial memory.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Ventral root avulsion leads to downregulation of GluR2 subunit in spinal motoneurons in adult rats.

It has been observed that motor neuron death is induced in adult rats by ventral root avulsion which involves pulling out the spinal cord root. Since motor neurons are reported to be selectively vulnerable to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor-mediated injury in vitro, we investigated changes in the expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate-receptor subunits in rat spinal motor neurons after ventral root avulsion. The L4-L5 ventral roots of adult Sprague-Dawley rats were avulsed by an extravertebral extraction procedure. After an appropriate survival time, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate-receptor subunits were detected immunohistochemically in the L4-L5 segments. Ventral root avulsion resulted in a 60% loss of motor neurons by 14 days after surgery. GluR2 labeling in motor neurons was markedly decreased after avulsion, but before the onset of motor neuron death, while the GluR1 and GluR4 labeling of motor neurons remained unchanged. Intrathecal administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate-receptor antagonists rescued a significant number of injured motor neurons from cell death. In contrast, N-methyl-D-aspartate-receptor antagonists did not prevent motor neuron death. Since the presence of GluR2 subunit renders heteromeric alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors Ca(2+)-impermeable, the downregulation of GluR2 may result in increased formation of GluR2-lacking, Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors in motor neurons and could contribute to motor neuron death after ventral root avulsion.

Animals↗

Superior antitumour activity of S-1 in tumours with a high dihydropyrimidine dehydrogenase activity.

To elucidate the mechanism of the enhanced antitumour activity of S-1 (1 M tegafur, 0.4 M 5-chloro-2, 4-dihydroxypyridine, and 1 M potassium oxonate) in terms of the phosphorylation and degradation pathways of 5-fluorouracil (5-FU) metabolism, we investigated tumoral thymidylate synthase (TS) content, dihydropyrimidine dehydrogenase (DPD) activity, the TS inhibition rate (TS-IR), and 5-FU incorporated into RNA (F-RNA) in four human gastric cancer xenografts (MKN-28, MKN-74, GCIY and GT3TKB) and compared the results obtained with S-1 with those obtained with 5-FU and UFT (1 M tegafur, 4 M uracil). 5-FU was administered intraperitoneally (i.p.) to mice at a dose of 50 mg/kg, three times, on days 0, 4 and 8. S-1 and UFT were administered orally at doses of 10 and 24 mg/kg, respectively, once a day, for 9 consecutive days. Antitumour activity was evaluated as the maximum inhibition of tumour growth in each animal. S-1 showed a better antitumour activity than 5-FU and UFT in tumours with a high DPD activity (GCIY and GT3TKB). There were inverse correlations between the antitumour activity and both TS content and DPD activity in the 5-FU and UFT groups. However, no such correlations were observed in the S-1 group. In GCIY and GT3TKB xenografts, TS-IR was significantly higher in the S-1 group than in the 5-FU or UFT groups. In GT3TKB xenografts, the F-RNA level was significantly higher in the S-1 group than in the 5-FU or UFT groups. The superior cytotoxicity of S-1 appears to be attributable to both an increased inhibition of DNA synthesis and an enhanced blockade of RNA function against tumours with a high DPD activity.

Animals↗

Nerve growth factor beta(NGF beta) delivery via a collagen/hydroxyapatite (Col/HAp) composite and its effects on new bone ingrowth.

In craniofacial surgery, bone is needed to augment misshapen areas and to fill gaps during repair of congenital anomalies and injuries resulting into bone deficiencies. Examples of conditions requiring bone tissue include missing alveolar bone in cleft palates, bony nasal pyramid defects following removal of fistulous tracts or cysts and defects following removal of sinus and mandibular tumors. Moreover, maxillofacial neurosensory deficiencies may be caused by various surgical procedures, such as tooth extraction, osteotomies, pre-prosthetic procedures, excision of tumors or cysts, surgery of TMJ, and surgical treatment of fractures and cleft lip/palate. Therefore, a tissue engineering approach to craniofacial surgery has a crucial importance: the use of various composites with osteoconductive ceramics, polymers, bioactive factors, cells, or a combination of them, offers the possibility of rapid tissue regeneration and integration with the host tissue. In this study, a composite consisting of two well-known biomaterials, collagen/hydroxyapatite (Col/HAp), was used as a drug delivery device for neurotrophin - nerve growth factor beta (NGF beta). This delivery device, enriched with neurogenic-osteogenic factor, was analyzed in vitro and in vivo. It was implanted into calvaria defects of 20 Wistar rats, weighing 200-250 g. Implants were left in place for different periods of time. Controls were as follows: (a) contralateral defect without any implant; and (b) contralateral defect implanted with composite without NGF factor. The rats were euthanized after 30 days, and the implant sites and explants were examined clinically, histologically, SEM and histomorphometrically. Our results evidenced stimulation of periosteal and endocortical woven and lamellar bone formation, with increases in bone mass and decreases in bone marrow. We found that NGF enhanced the remodeling activity in the intracortical region, and induced an increase in the intracortical cavity number and area by the end of the study. In vitro results were in line with in vivo ones. We believe that the composite proposed in this study has considerable advantages in tissue engineering and is very suitable as a biomaterial for the filling of irregular defects in maxillo-facial surgery. Two areas of clinical research will be impacted by this system. The first is pharmaceutical research on drug delivery and high-throughput screening of neurotrophic-osteogenic compounds. Transplantation research is the second area that will benefit from the system.

Journal Article↗

Accumulation of CCR4-expressing CD4+ T cells and high concentration of its ligands (TARC and MDC) in bronchoalveolar lavage fluid of patients with eosinophilic pneumonia.

BACKGROUND: Th2 cells are thought to be involved in eosinophilic inflammation of the lung. CC chemokine receptor 4 (CCR4) has been identified as a specific receptor for both thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC), and is preferentially expressed on Th2 cells. OBJECTIVE: Our aim was to evaluate the role of Th2 cells in the lung of patients with eosinophilic pneumonia (EP). METHODS: The concentrations of TARC, MDC, and interleukin (IL)-5 were measured in bronchoalveolar lavage fluid (BALF) by ELISA. Proportion of CCR4-expressing CD4+ T cells (CCR4+ CD4+ T cells) was determined by flow cytometry. RESULTS: TARC and MDC concentrations in BALF were higher in patients with EP than in normal subjects. The proportion of CCR4-expressing cells among CD4+ T cells was higher in BALF than in peripheral blood of patients with EP. There was a significant correlation between the number of CCR4+ CD4+ T cells and the levels of TARC, MDC, and IL-5 in BALF of patients with EP. CONCLUSIONS: Our data suggest that Th2 cells, which express CCR4 and its ligands (TARC and MDC), contribute to the pathogenesis of EP in the lung.

Adult↗

Biochemical and functional properties of a pyruvate formate-lyase (PFL)-activating system in Streptococcus mutans.

Streptococcus mutans has an oxygen-sensitive enzyme, pyruvate formate-lyase (PFL), which is a key enzyme in anaerobic sugar fermentation. We have shown that S. mutans has an activating system, including a PFL-activating enzyme (PFL-activase) and an electron transport system; the latter transfers an electron from NADPH to PFL-activase, as occurs in Escherichia coli. NADPH was a physiological electron donor for the electron transport system and as little as 0.02 mM NADPH activated over 80% of PFL of S. mutans. The optimum pH of the PFL-activating system was around 6.8, whereas the optimum of the E. coli system is at alkaline pH. In addition, small dialyzable molecules in cell-free extracts participated in keeping PFL active in S. mutans. These results suggest that, in dental plaque under anaerobic conditions where sugar supply is often limited or pH frequently falls below neutrality, S. mutans always keeps PFL active through the activating system.

Acetyltransferases↗

Telomerase inhibition enhances apoptosis in human acute leukemia cells: possibility of antitelomerase therapy.

Telomerase is a ribonucleoprotein enzyme that maintains protective structures at the ends of eukaryotic chromosomes. We examined the impact of telomerase inhibition by the dominant-negative human catalytic subunit of telomerase (DN-hTERT) on the biological features of acute leukemia. We introduced vectors encoding dominant- negative (DN)-hTERT, wild-type (WT)-hTERT, or a control vector expressing only a drug-resistant marker into a telomerase-positive human acute lymphoblastic leukemia cell line, HAL-01. Expression of DN-hTERT dramatically inhibited telomerase activity, leading to apoptotic cell death. Mutant telomerase expression also enhanced daunorubicin-induced apoptosis. Nude mice (n=5 per group) received subcutanous implants of HAL-01 cells expressing the control vector or DN-hTERT or WT-hTERT. Implantation of HAL-01 cells expressing control vector (n=5) rapidly produced tumors, whereas implantation of those expressing DN-hTERT (n=5) did not. Thus, telomerase inhibition both growth of HAL-01 cells in vitro and tumorigenic capacity in vivo. Furthermore, the G-quadruplex-interactive telomerase-specific inhibitor, telomestatin, shortened the telomere length and induced apoptosis in freshly isolated primary acute leukemia cells. These results suggest that antitelomerase therapy may be useful in some acute leukemias in combination with antileukemic agents such as daunorubicin.

Acute Disease↗

Coping strategies and its effects on depression among caregivers of impaired elders in Japan.

The purpose of this study was to explore the coping strategies of Japanese family caregivers and to investigate relationships between coping strategies, caregiving stressors,and family caregivers' mental health. We conducted a survey by mail among family members who provided care for physically or mentally impaired elderly. In this study, we used 166 responses from family caregivers for analysis. Results of exploratory and confirmatory factor analysis indicated three factors,categorized 'Resignation,' 'Consulting and complaining' and 'Distancing'. In addition, results of structure equation modelling suggested a significant effect of 'Resignation' on the mental health of caregivers. Although the factor structure of coping strategies was similar to other studies conducted in Western countries, the effects of coping strategies were quite different. In conclusion, the effects of coping strategies on caregivers' mental health were confirmed in this study, but different types of coping strategies from those of Western countries were found to be associated with mental health of Japanese family caregivers.

Activities of Daily Living↗

Comparison of iridial pigmentation between latanoprost and isopropyl unoprostone: a long term prospective comparative study.

AIM: To compare incidence of iridial pigmentation prospectively induced by long term treatment with latanoprost and isopropyl unoprostone (hereafter, unoprostone) in Japanese patients with glaucoma. METHODS: Patients with glaucoma treated with prostaglandin (PG) related ophthalmic solutions were sequentially enrolled. Patients treated for more than 30 months with PG related ophthalmic solutions were subjected to analysis. The entry criteria were no history of intraocular surgery, laser iridotomy, and/or laser trabeculoplasty within 12 months before and after the enrolment; and no history of uveitis; no changes in antiglaucoma drugs within 6 months before and after the enrolment. Photographs of the irides were taken under the same conditions and three glaucoma specialists evaluated the iridial pigmentation with masking of patient information. The correlation of iridial pigmentation with the background factors and the reduction of intraocular pressure (IOP) before and after the treatment were investigated. RESULTS: 48 eyes in 48 patients satisfied the enrolment criteria (25 eyes in the latanoprost group, 23 eyes in the unoprostone group). At the end of the follow up period, iridial pigmentation was present in 15 patients (60.0%) in the latanoprost group and seven patients (30.4%) in the unoprostone group. The correlation between development of iridial pigmentation and age, sex, concurrent use of other ophthalmic solutions, and IOP reduction was not significant. CONCLUSIONS: The incidence of iridial pigmentation induced by latanoprost or unoprostone is high in the case of long term treatment. Iridial pigmentation did not affect PG related ophthalmic solution induced IOP reduction.

Adult↗

High serum concentrations of surfactant protein A in usual interstitial pneumonia compared with non-specific interstitial pneumonia.

BACKGROUND: The pathological diagnosis of interstitial lung diseases (ILD) by surgical lung biopsy is important for clinical decision making. There is a need, however, to use serum markers for differentiating usual interstitial pneumonia (UIP) from other ILD. Surfactant protein (SP)-A, SP-D, KL-6, sialyl SSEA-1 (SLX), and sialyl Lewis(a) (CA19-9) are useful markers for the diagnosis and evaluation of activity of ILD. We have investigated the usefulness of these proteins as markers of UIP. METHODS: Serum and bronchoalveolar lavage (BAL) fluid levels of the above five markers were measured in 57 patients with various forms of ILD (19 with UIP, 12 with non-specific interstitial pneumonia (NSIP), eight with bronchiolitis obliterans organising pneumonia (BOOP), and 10 with sarcoidosis), eight patients with the control disease (diffuse panbronchiolitis (DPB)), and nine healthy volunteers. RESULTS: Serum levels of SP-A, SP-D, and KL-6 in patients with UIP and NSIP were significantly higher than in healthy volunteers. In particular, the serum levels of SP-A in patients with UIP were significantly higher than in patients with NSIP (p<0.0001, mean difference -58.3 ng/ml, 95% confidence interval -81.6 to -35.0), and BAL fluid levels of SP-D in patients with UIP were significantly lower than in patients with NSIP (p=0.01, mean difference 322.4 ng/ml, 95% confidence interval 79.3 to 565.5). CONCLUSION: Serum SP-A levels may be clinically useful as a biomarker to differentiate between UIP and NSIP.

Adult↗

Temporal and spacial changes of highly polysialylated neural cell adhesion molecule immunoreactivity in amygdala kindling development.

To investigate the migration of neural stem cells as well as neural plastic changes in epileptic brain, spaciotemporal expression of immunoreactive highly polysialylated neural cell adhesion molecule (PSA-NCAM) was examined in amygdala kindling development of rat. The neural migration and synaptic remodeling detected with PSA-NCAM staining occurred in dentate gyrus of hippocampus, subventricular zone and pyriform cortex with amygdaloid kindling in generalized seizure but not in partial seizure. Although PSA-NCAM positive dendrite in dentate gyrus was minimally found in the control brain, it extended slightly in animals with partial seizure, and greatly toward the molecular layer with generalized seizure. Thus, the migration of neural stem cells as well as neural plastic changes were specially and temporally different between brain regions depending on different kindling stages. These changes may mainly contribute to the reorganization of neural network in epileptic brain.

Amygdala↗

Glial cell line-derived neurotrophic factor protein prevents motor neuron loss of transgenic model mice for amyotrophic lateral sclerosis.

Effects of glial cell line-derived neurotrophic factor (GDNF) were studied in transgenic (Tg) mice model for amyotrophic lateral sclerosis. GDNF protein or vehicle was injected three times a week from 35 weeks of age into the right gastrocnemius muscle of Tg mice carrying mutant human Cu/Zn superoxide dismutase gene, and histological analysis was performed at 46 weeks. Clinical data showed a tendency of improvement, but was not significantly different between the two animal groups. In contrast, total number of and phospho-Akt (p-Akt) positive large motor neurons in the treated side was significantly more preserved in GDNF-treated group than in vehicle group (p < 0.05). Immunoreactivity of phospho-ERK and active caspases-3 and -9 showed no difference. These results indicate that the intramuscular injection of GDNF protein prevented motor neuron loss while preserving survival p-Akt signal and without affecting caspase activations, suggesting a future possibility for the therapy of the disease.

Amyotrophic Lateral Sclerosis↗