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K Nagashima

Publications and source records attributed to K Nagashima.

At least 19 recordsLinked to original sources
PubMed2006

Involvement of adaptor protein Crk in malignant feature of human ovarian cancer cell line MCAS.

Signaling adaptor protein Crk regulates cell motility and growth through its targets Dock180 and C3G, those are the guanine-nucleotide exchange factors (GEFs) for small GTPases Rac and Rap, respectively. Recently, overexpression of Crk has been reported in various human cancers. To define the role for Crk in human cancer cells, Crk expression was targeted in the human ovarian cancer cell line MCAS through RNA interference, resulting in the establishment of three Crk knockdown cell lines. These cell lines exhibited disorganized actin fibers, reduced number of focal adhesions, and abolishment of lamellipodia formation. Decreased Rac activity was demonstrated by pull-down assay and FRET-based time-lapse microscopy, in association with suppression of both motility and invasion by phagokinetic track assay and transwell assay in these cells. Furthermore, Crk knockdown cells exhibited slow growth rates in culture and suppressed anchorage-dependent growth in soft agar. Tumor forming potential in nude mice was attenuated, and intraperitoneal dissemination was not observed when Crk knockdown cells were injected into the peritoneal cavity. These results suggest that the Crk is a key component of focal adhesion and involved in cell growth, invasion, and dissemination of human ovarian cancer cell line MCAS.

Actin Cytoskeleton↗
PubMed2006

Mutant murine leukemia virus Gag proteins lacking proline at the N-terminus of the capsid domain block infectivity in virions containing wild-type Gag.

We have investigated the properties of murine leukemia virus Gag mutants in which the p12-CA cleavage site is altered. In one mutant, the cleavage is blocked; in the other, the conserved proline at the N-terminus of CA has been replaced with glycine. No infectivity was detected in either mutant. Mutant particles cannot synthesize full-length DNA upon infecting permissive cells. Particles composed of a mixture of wild-type and mutant proteins have severely impaired infectivity. These mixed particles are defective in their ability to synthesize DNA upon infection, but this defect is less severe than the loss of infectivity. Thus, proteins lacking the correct N-terminus of CA inhibit DNA synthesis and also interfere with formation or integration of a full-length, normal provirus. The results imply that CA proteins function as part of a large, highly organized structure in reverse transcription and apparently at a later step as well.

Animals↗
PubMed2005

Acute effects of ethanol on hippocampal long-term potentiation and long-term depression are mediated by different mechanisms.

To determine potential mechanisms contributing to ethanol-induced cognitive impairment, we examined acute effects of ethanol on hippocampal N-methyl-d-aspartate receptors and forms of synaptic plasticity thought to underlie memory processing. In the CA1 region of rat hippocampal slices, ethanol partially inhibited N-methyl-d-aspartate receptor-mediated synaptic responses at concentrations up to 180 mM. The block of synaptic N-methyl-d-aspartate receptors by 60mM ethanol occluded the effects of 10 microM ifenprodil, an agent that has relative selectivity for N-methyl-D-aspartate receptors expressing NR1 and NR2B subunits. Ethanol did not occlude the effects of a low concentration of 2-amino-5-phosphonovalerate, an antagonist with less N-methyl-d-aspartate receptor subtype selectivity. Recent studies indicate that ifenprodil and other NR2B-selective antagonists inhibit N-methyl-D-aspartate receptor-dependent long-term depression but not long-term potentiation. We found that ethanol reversibly inhibited long-term depression in a manner consistent with its effects on synaptic N-methyl-D-aspartate receptors. Ethanol also inhibited the induction of N-methyl-D-aspartate receptor-dependent long-term potentiation, but the actions on long-term potentiation were complex and largely irreversible over the time course of our experiments. Furthermore, ethanol inhibited a form of long-term potentiation induced by very high frequency stimulation that does not depend on N-methyl-D-aspartate receptor activation. The effects of ethanol on both forms of long-term potentiation, but not on long-term depression, were at least partially reversed by block of GABA type A receptors with picrotoxin. These results indicate that pharmacologically relevant concentrations of ethanol exert preferential effects on a subtype of synaptic N-methyl-D-aspartate receptors in the CA1 hippocampal region. Inhibition of synaptic N-methyl-D-aspartate receptors appears to contribute strongly to ethanol-mediated long-term depression inhibition, but effects on long-term potentiation are complex, involving, at least partially, changes in GABAergic transmission.

Animals↗
PubMed2005

Fos activation in hypothalamic neurons during cold or warm exposure: projections to periaqueductal gray matter.

The hypothalamus, especially the preoptic area, plays a crucial role in thermoregulation, and our previous studies showed that the periaqueductal gray matter is important for transmitting efferent signals to thermoregulatory effectors in rats. Neurons responsible for skin vasodilation are located in the lateral portion of the rostral periaqueductal gray matter, and neurons that mediate non-shivering thermogenesis are located in the ventrolateral part of the caudal periaqueductal gray matter. We investigated the distribution of neurons in the rat hypothalamus that are activated by exposure to neutral (26 degrees C), warm (33 degrees C), or cold (10 degrees C) ambient temperature and project to the rostral periaqueductal gray matter or caudal periaqueductal gray matter, by using the immunohistochemical analysis of Fos and a retrograde tracer, cholera toxin-b. When cholera toxin-b was injected into the rostral periaqueductal gray matter, many double-labeled cells were observed in the median preoptic nucleus in warm-exposed rats, but few were seen in cold-exposed rats. On the other hand, when cholera toxin-b was injected into the caudal periaqueductal gray matter, many double-labeled cells were seen in a cell group extending from the dorsomedial nucleus through the dorsal hypothalamic area in cold-exposed rats but few were seen in warm-exposed rats. These results suggest that the rostral periaqueductal gray matter receives input from the median preoptic nucleus neurons activated by warm exposure, and the caudal periaqueductal gray matter receives input from neurons in the dorsomedial nucleus/dorsal hypothalamic area region activated by cold exposure. These efferent pathways provide a substrate for thermoregulatory skin vasomotor response and non-shivering thermogenesis, respectively.

Animals↗
PubMed2004

Picosecond view of microscopic-scale polarization clusters in paraelectric BaTiO3.

The polarization clusters existing in both the ferroelectric and the paraelectric phase of BaTiO3 are directly observed and characterized for the first time by a picosecond soft x-ray laser speckle technique. These dynamic clusters appear continuously across the Curie temperature T(c). The clusters' distance increases approximately linearly with temperature, while their mean size does not change significantly. The polarization exhibits a maximum at a temperature about 5 degrees C above T(c). The clusters' short-range correlation strength diverges as (T-T(c))(-0.41+/-0.02) as temperature decreases toward T(c).

Journal Article↗
PubMed2004

Clinical significance and usefulness of quantification of telomerase activity in oral malignant and nonmalignant lesions.

We quantified telomerase activity (TA) in patients with oral and maxillofacial malignant and nonmalignant lesions, and compared it with their clinical status and grade of malignancy. Fifty-two malignant and 52 nonmalignant lesions were analyzed. All malignant lesions were pathologically diagnosed as oral squamous cell carcinoma (OSCC). Normal gingival tissue served as a control. These specimens were obtained by biopsy or surgical resection, and stored at -80 degrees C until use. TA was quantified by a fluorescence-based TRAP method. TA levels ranged from 0.00 to 95.24 (average 33.24)U/microgP in 52 malignant lesions, and from 0.00 to 79.35 (average 11.91)U/microgP in 52 nonmalignant lesions (P < 0.0001). TA was detected in 96.2% of malignant and 65.4% of nonmalignant lesions. There was no relationship between TA levels and clinical stages or YK classification. However, under WHO classification, there were significant differences (P < 0.05) between Grades I and III or II + III. Among nonmalignant lesions, epithelial dysplasia showed a significantly higher TA level than that of oral lichen planus (P < 0.05) and other benign lesions (P < 0.0001). Oral lichen planus also significantly differed from other benign lesions (P < 0.05). These results suggest that TA is related to the histological grade of malignancy, and is also useful as a prognostic predictor for precancerous lesions and conditions.

Acid Phosphatase↗
PubMed2004

Multifocal angiomyolipoma affecting the liver and lung without tuberous sclerosis.

The occurrence of angiomyolipoma (AML) in tissue other than the kidney is uncommon, as is multiple AML developing exclusively in organs other than the kidney. This report describes a case in which AML occurred multifocally in the liver and lung, but spared the kidney, and which might have been associated with tuberous sclerosis complex (TSC). A Japanese woman underwent a partial hepatectomy for a suspected malignant liver tumour at the age of 57. The tumour consisted predominantly of a trabecular arrangement of myoid cells with a sinusoidal pattern and inflammatory cell infiltration, and was diagnosed as a primary liver AML by HMB-45 immunoreactivity. Five years later, multiple nodules were found in both lungs, for which video assisted thoracic surgery was performed. The tumour showed a mixture of epithelioid cells containing HMB-45 positive material and mature lipocytes, and was subsequently diagnosed as AML. Molecular analysis of both lesions showed no allelic loss of the TSC1 and TSC2 regions. Molecular analysis of the tumours ruled out an association with TSC, and both liver and lung lesions displayed benign histological features, so that these were probably multifocal lesions of AML without TSC.

Angiomyolipoma↗
PubMed2003

The melanocyte inducing factor MITF is stably expressed in cell lines from human clear cell sarcoma.

Clear cell sarcoma (CCS) is associated with the EWS/ATF1 oncogene that is created by chromosomal fusion of the Ewings Sarcoma oncogene (EWS) and the cellular transcription factor ATF1. The melanocytic character of CCS suggests that the microphthalmia-associated transcription factor (Mitf), a major inducer of melanocytic differentiation, may be miss-expressed in CCS. Accordingly, we show that the mRNA and protein of the melanocyte-specific isoform of Mitf (Mitf-M) are present in several cultured CCS cell lines (Su-ccs-1, DTC1, Kao, MST-1, MST-2 and MST-3). The above cell lines thus provide a valuable experimental resource for examining the role of Mitf-M in both CCS and melanocyte differentiation. Melanocyte-specific expression of Mitf-M is achieved via an ATF-dependent melanocyte-specific cAMP-response element in the Mitf-M promoter, and expression of Mitf-M in CCS cells suggests that EWS/ATF1 (a potent and promiscuous activator of cAMP-inducible promoters) may activate the Mitf-M promoter. Surprisingly, however, the Mitf-M promoter is not activated by EWS/ATF1 in transient assays employing CCS cells, melanocytes or nonmelanocytic cells. Thus, our results indicate that Mitf-M promoter activation may require an appropriate chromosomal context in CCS cells or alternatively that the Mitf-M promoter is not directly activated by EWS/ATF1.

Blotting, Western↗
PubMed2003

Long-term therapeutic effects of voglibose, a potent intestinal alpha-glucosidase inhibitor, in spontaneous diabetic GK rats.

The effect of long-term (6 months) administration of voglibose in a dietary mixture (10 ppm) on intestinal disaccharidase activity was examined in non obese type 2 diabetes model Goto-Kakizaki (GK) rats. The postprandial blood glucose level in voglibose-treated GK rats was significantly lower than in untreated GK rats (190+/-19 vs. 250+/-25 mg/dl, P<0.01; 1 h, 212+/-23 vs. 256+/-20, P<0.05; 2 h), and the activities of maltase, sucrase, and isomaltase remained significantly lower throughout the 6 months of voglibose treatment. The expressions of protein and mRNA of sucrase-isomaltase (SI) complex were significantly higher in voglibose-treated GK rats. Voglibose administration then was stopped after 6 months of treatment. The mRNA level and protein level of the SI complex became normalized during the interruption of drug administration, and disaccharidase activities increased almost to the level of the untreated group 1 month after treatment was stopped. After 1 day of re-administration of the drug, however, disaccharidase activities again became significantly inhibited. These results indicate that voglibose may improve glucose tolerance since it inhibits activities of disaccharidases in spite of increasing the expression of them on intestine, furthermore voglibose may be reversible and reproducible through interruption and re-administration.

Alkaline Phosphatase↗
PubMed2003

Effects of an aldose reductase inhibitor on gastroenteropathy in streptozotocin-diabetic rats.

We investigated the effects of epalrestat, an aldose reductase inhibitor (ARI), on gastric emptying, fecal water content, and electrolyte transport in distal colon in streptozotocin (STZ)-induced diabetic rats. We measured gastric emptying time by acetaminophen method and short-circuit-current (Isc) in colonic mucosa using an Ussing chamber. The Isc in response to electric-field-stimulation (EFS) was decreased in untreated rats due to suppression by Cl- secretion. ARI treatment alleviated this suppression (2.7 +/- 0.6 vs. 7.4 +/- 1.1 microA/0.38 cm2 at 8 weeks after treatment, 1.1 +/- 0.2 vs. 7.0 +/- 1.0 at 12 weeks after treatment, P<0.05). In addition, the percentage of fecal water content in untreated rats was significantly lower than in ARI-treated rats (58.0 +/- 2.0 vs. 67.6 +/- 0.8% at 8 weeks, 56.9 +/- 2.1 vs. 63.4 +/- 1.4 at 12 weeks, P<0.05). From STZ injection to 8 weeks, the serum levels of acetaminophen in the diabetic rats were significantly lower than in controls, indicating delayed gastric emptying. At 12 weeks in the diabetic rats treated with ARI, the serum levels of acetaminophen were significantly higher than in the untreated diabetic rats (6.6 +/- 0.4 vs. 3.5 +/- 0.5 microg/ml, P<0.05). ARI-treatment ameliorated delayed gastric emptying without improving glycemic control. These findings show that ARI partially prevented progression of impaired gastric emptying, ion transport, and water transport, and suggest that epalrestat might be useful in the treatment of diabetic gastroenteropathy.

Acetaminophen↗
PubMed2002

Picosecond snapshot of the speckles from ferroelectric BaTiO3 by means of x-ray lasers.

A picosecond x-ray laser speckle has been conducted to study the dynamics of a disordered surface domain structure (BaTiO3 with 90 degrees c/a domains) as a function of temperature for the first time. The transient surface structures induced by ferroelectric domains decrease as temperature increases towards the Curie temperature T(c) and completely disappear above T(c). The dramatic change of the spatial configuration of the c/a domains was observed to occur from a temperature 2 degrees C below T(c), near which the average correlated domain size at equilibrium decreases as (T(c)-T)(0.37+/-0.02).

Journal Article↗
PubMed2002

Effect of local hyperthermia on metastases in oral squamous cell carcinoma.

In this experimental study, hamsters with oral squamous cell carcinoma (O-1N), which has a high potential for lymph node metastasis, received treatment with local hyperthermia. The effect of hyperthermia on regional lymph node metastases was examined pathologically. O-1N was heated twice, each session consisting of radiofrequency capacitive heating (13.56 MHz) for 40 min at 43 degrees C. Cervical lymph nodes were excised 14, 17, 21, and 28 days after heating and were examined histologically. Hamsters in the sham and control groups were killed on the same days and specimens were examined in a same manner. The incidence of lymph node metastasis was significantly lower in the hyperthermia group (36.4%) than in the sham (68.5%) and control (65.0%) groups (both P=0.02). The patterns of lymph node metastasis in the sham and control groups were more advanced than that in the hyperthermia group. The incidence of lymph node metastasis was very low (7.7%) in hamsters with no evidence of tumour after hyperthermia. On multivariate analysis, hyperthermia correlated with inhibition of cervical lymph node metastasis (P=0.02). Our findings suggest that local hyperthermia inhibits lymph node metastasis when the primary tumour responds histologically to treatment.

Animals↗
PubMed2002

Changes regarding age and correlations between serum lipids and body mass index in humankind.

OBJECTIVES: To improve insight into age and gender related distributions of serum lipids and their correlation with body mass index (BMI). METHODS: Serum lipids embracing atherogenic index (AI) and BMI were analyzed from the results obtained in 19,823 men and 14,788 women undergoing a health examination between 1986 and 1996. RESULTS: The changes in total cholesterol (TC), triglyceride (TG), AI and BMI differed regarding gender. Although high-density lipoprotein-cholesterol (HDL-C) showed a flat pattern for all ages in both genders, its level in women was higher than in men. The ratio of the number in the unsuitable range to those in the suitable range increased with age as to TC in both sexes, then more than half of the population have an unsuitable level in the sixth decade. As for the correlation between serum lipids and BMI: TC, TG and AI correlated positively, but HDL-C correlated negatively. There were significant gaps between both age and gender. CONCLUSIONS: We suggest that the normal range of values of serum lipids needs to be revised according to gender and age to evaluate the risk status for a cardio-cerebrovascular disease more precisely in the field of preventive medicine. Simpler guidelines are preferable in specialized care as well as in general practice, particularly since computer technology is not yet universally adapted. In the near future, when computed information technology will be as common as the electricity and the telephone are current on the whole earth, all guidelines will have to be computed on the spot and personally.

Adult↗
PubMed2001

Expression of glial cell line-derived neurotrophic factor induced by transient forebrain ischemia in rats.

This study examined the expression of glial cell line-derived neurotrophic factor (GDNF) mRNA and the cellular localization of GDNF production in rats subjected to transient forebrain ischemia induced by four-vessel occlusion. Transient forebrain ischemia induced GDNF mRNA expression in the hippocampus from 3 h to 3 days after the ischemic episode, with peak expression at 6 h. The GDNF mRNA increase in the cerebral cortex was similar to that in the hippocampus, whereas no increase in GDNF mRNA was observed in the striatum and brainstem. Western blot analysis showed that GDNF in the hippocampal CA1 region was increased slightly from 3 to 24 h after the ischemia, and then subsequently declined to below the baseline level. In the hippocampus, GDNF was evenly produced in pyramidal neurons of both sham-operated rats and normal rats, as determined by immunohistochemistry. Interestingly, we found that ischemia-induced reactive astrocytes, as well as surviving neurons, produced GDNF in 3-7 days after the ischemia. On the other hand, in other regions, such as the cerebral cortex, striatum, and brainstem, there was no change in GDNF-positive cells secondary to ischemia. These findings suggest that expression of GDNF mRNA is regulated in part via ischemia-induced neuronal degeneration. They also suggest that ischemia-induced reactive astrocytes may produce GDNF to protect against neuronal death. Therefore, GDNF may play an important role in ischemia-induced neuronal death in the brain.

Animals↗
PubMed2001

Numerical study of laser wake field generated by two colliding laser beams.

The laser wake field generated by two colliding laser beams has been studied numerically. The wake field amplitude is enhanced by a counterpropagating long pulse laser, which has an appropriate frequency difference, and becomes an order of magnitude larger than that of the standard wake field. The field amplitude increases in proportion to the pumping laser intensities until it saturates under the wave breaking limit. The details of the enhanced wake field have been examined at the saturated state.

Journal Article↗