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Biomedical subjects

H Yano

Publications and source records attributed to H Yano.

At least 19 recordsLinked to original sources

The CCR4 as a novel-specific molecular target for immunotherapy in Hodgkin lymphoma.

Here, we report that tumor cells from some patients (23.8%) with Hodgkin lymphoma (HL) are positive for CC chemokine receptor 4 (CCR4). We therefore tested the chimeric anti-CCR4 monoclonal antibody (mAb), KM2760, the Fc region of which is defucosylated to enhance antibody-dependent cellular cytotoxicity (ADCC), as a novel immunotherapy for refractory HL. KM2760 demonstrated a promising antitumor activity in the CCR4-positive HL-bearing mouse model in the therapeutic setting. Although KM2760 did not induce any ADCC mediated by mouse natural killer (NK) cells, it significantly enhanced phagocytosis mediated by mouse monocytes/macrophages against the CCR4-positive HL cell line in vitro. Together with the findings that KM2760 did not exhibit any complement-dependent cytotoxicity or direct antiproliferation activity in vitro, these data indicated that KM2760 exerted its robust in vivo antitumor activity via monocytes/macrophages in mice. In the human system, KM2760 enhanced phagocytic activity mediated by monocytes/macrophages. Furthermore, it induced robust ADCC mediated by NK cells against the CCR4-positive HL cell line in vitro. Thus, it is conceivable that KM2760 would have much more potent antitumor activity in humans than in mice. Collectively, this study strongly indicates that anti-CCR4 mAb could be a novel treatment modality for patients with CCR4-positive HL.

Animals↗

Molecular cloning and gene expression of a fibrillarin homolog of tobacco BY-2 cells.

Fibrillarin is known to play an important role in precursor ribosomal RNA processing and ribosome assembly. The present study describes a fibrillarin homolog gene isolated from tobacco BY-2 cells and its expression during the cell cycle. The cDNA for a fibrillarin homolog, named NtFib1, was first cloned in Nicotiana tabacum with degenerate primers. It encodes 314 amino acids and the deduced amino acid sequence has some highly conserved functional domains, such as the glycine and arginine-rich (GAR) domain for nucleolar localization and the RNA-binding motif. The C-terminal region is highly conserved and has 7 beta-sheets and 7 alpha-helices which are peculiar to fibrillarin. Thus, it is suggested that the fibrillarin homolog of this plant species functions in the same way as the fibrillarin already known from human and yeast cells. Northern blot analysis of BY-2 cells synchronized with aphidicolin or a combination of aphidicolin and propyzamide showed that the histone H4 gene was specifically expressed in the S phase but NtFib1 mRNA remained at high levels during the cell cycle. Examination of the localization of NtFib1 protein tagged with green-fluorescent protein (GFP) suggested that some persisting in the mitotic apparatus was eventually incorporated into reconstructed nucleoli in late telophase. Newly synthesized GFP-tagged NtFib1 protein in the cytoplasm was added to the recycled protein in early mitosis. Highly concentrated actinomycin D completely inhibited the transcription of genes coding for rRNA (rDNA) but did not significantly suppress the amount of either NtFib1 mRNA or protein, although the NtFib1 protein was reversibly dislocated from nucleoli. Although hypoxic shock completely prohibited rDNA transcription, NtFib1 mRNA remained at the same level as in the control experiment, even after the 4 h treatment. These results indicate that the transcription of NtFib1 mRNA is not related to rDNA transcription and NtFib1 mRNA is resistant to disrupting factors during the cell cycle.

Amino Acid Sequence↗

The rubble-pile asteroid Itokawa as observed by Hayabusa.

During the interval from September through early December 2005, the Hayabusa spacecraft was in close proximity to near-Earth asteroid 25143 Itokawa, and a variety of data were taken on its shape, mass, and surface topography as well as its mineralogic and elemental abundances. The asteroid's orthogonal axes are 535, 294, and 209 meters, the mass is 3.51 x 10(10) kilograms, and the estimated bulk density is 1.9 +/- 0.13 grams per cubic centimeter. The correspondence between the smooth areas on the surface (Muses Sea and Sagamihara) and the gravitationally low regions suggests mass movement and an effective resurfacing process by impact jolting. Itokawa is considered to be a rubble-pile body because of its low bulk density, high porosity, boulder-rich appearance, and shape. The existence of very large boulders and pillars suggests an early collisional breakup of a preexisting parent asteroid followed by a re-agglomeration into a rubble-pile object.

Journal Article↗

Spreds, inhibitors of the Ras/ERK signal transduction, are dysregulated in human hepatocellular carcinoma and linked to the malignant phenotype of tumors.

Aberrant activation of the Ras/Raf-1/extracellular-regulated kinase (ERK) pathway has been shown to be involved in the progression of human hepatocellular carcinoma (HCC). However, the mechanism of dysregulation of ERK activation is poorly understood. Recently, we identified Sprouty-related protein with Ena/vasodilator-stimulated phosphoprotein homology-1 domain (Spred) as a physiological inhibitor of the Ras/Raf-1/ERK pathway. In this study, we found that the expression levels of Spred-1 and -2 in human HCC tissue were frequently decreased, comparing with those in adjacent non-tumorous tissue. Moreover, Spred expression levels in HCC tissue were inversely correlated with the incidence of tumor invasion and metastasis. Forced expression of Spred-1 inhibited HCC cell proliferation in vitro and in vivo, which was associated with reduced ERK activation. Spred-1 overexpression also reduced the secretion of matrix metalloproteinase-9 (MMP-9) and MMP-2, which play important roles in tumor invasion and metastasis. In addition, Spred-1 inhibited growth factor-mediated HCC cell motility. These data indicate that the reduction of Spred expression in HCC is one of the causes of the acquisition of malignant features. Thus, Spred could be not only a novel prognostic factor but also a new therapeutic target for human HCC.

Adaptor Proteins, Signal Transducing↗

Phthalocyanine-dyed fibers adsorb allergenic proteins.

Phthalocyanine (Pc)-dyed fiber is reported to reduce atopic symptoms in some patients when they use underwear made of the fiber. We investigated the adsorption of allergens on Pc-fiber. Pc-fiber trapped house dust/pollen/food allergens with varied molecular weight and pI. The adsorbed allergens were released in the presence of mild detergent. Pc-fiber did not change the molecular weight or disulfide bonding of the allergens. These observations imply that Pc-fiber is applicable as an "allergen trap" for a wide variety of products.

Adsorption↗

Bos indicus type of growth hormone receptor gene is retained in Japanese Black cattle.

The growth hormone receptor (GHR) gene is responsible for growth and carcass traits, and polymorphisms associated with the variation of meat production are thought to occur in the liver-specific promoter of the GHR gene in cattle. The aim of this study was to analyse the structure of the liver-specific promoter of GHR in Japanese Black cattle, as the relationship between GHR polymorphism and meat production is poorly understood in this breed. Typically in European cattle, the LINE-1 element, a family of retrotransposons, is inserted in the liver-specific promoter. However, a short GHR promoter without the LINE-1 sequence was found in the Japanese Black breed as in Bos indicus cattle. The frequency of the short allele was approximately 60%. In addition, 24 of 29 Holstein/Japanese Black crosses carried the short allele from their sire. The present result suggests that the short allele for GHR may be a candidate marker for improving meat production of Japanese Black cattle.

Alleles↗

Characterization of low-molecular-weight glutenin subunit genes and their protein products in common wheats.

To characterize the low-molecular-weight glutenin subunit (LMW-GS), we developed specific PCR primer sets to distinguish 12 groups of LMW-GS genes of Norin 61 and to decide their loci with nullisomic-tetrasomic lines of Chinese Spring. Three, two, and ten groups were assigned to Glu-A3, Glu-B3, and Glu-D3 loci, respectively. To identify the proteins containing the corresponding amino acid sequences, we determined the N-terminal amino acid sequence of 12 spots of LMW-GSs of Norin 61 separated by two-dimensional gel electrophoresis (2DE). The N-terminal sequences of the LMW-GS spots showed that 10 of 12 groups of LMW-GSs were expressed as protein products, which included LMW-i, LMW-m, and LMW-s types. Four spots were encoded by Glu-A3 (LMW-i). Three spots were encoded by Glu-B3 (LMW-m and LMW-s). Five spots were encoded by Glu-D3 (LMW-m and LMW-s). A minor spot of LMW-m seemed to be encoded by the same Glu-B3 gene as a major spot of LMW-s, but processed at a different site. Comparing among various cultivars, there were polymorphic and non-polymorphic LMW-GSs. Glu-A3 was highly polymorphic, i.e., the a, b, and c alleles showed one spot, the d allele showed four spots, and the e allele had no spot. Insignia used as one of the Glu-A3 null standard cultivars had a LMW-GS encoded by Glu-A3. We also found that Cheyenne had a new Glu-D3 allele. Classification of LMW-GS by a combination of PCR and 2DE will be useful to identify individual LMW-GSs and to study their contribution to flour quality.

Amino Acid Sequence↗

Laparoscopic management for local recurrence of early gastric cancer after endoscopic mucosal resection.

Endoscopic mucosal resection (EMR) is a widely accepted technique for early gastric cancer because it is minimally invasive; however, incomplete resection with subsequent cancer recurrence in the remnant remains a difficult problem. Generally, the margins of the local recurrence lesions are unclear, and second EMR is difficult to perform because of scar formation after the first EMR. We performed a laparoscopic treatment on six patients with residual lesions after EMR and reviewed the safety and efficacy of this management. Laparoscopic management consisted of two techniques: laparoscopic wedge resection with a lesion-lifting method and laparoscopic-assisted distal gastrectomy with mini-laparotomy. Cancerous lesions were completely resected with sufficient surgical margins circumferentially. Mean operative time was 171 min, mean estimated blood loss was 16.5 g, time to first walking was 1 day, duration of epidural analgesia was 2.2 days, and mean length of hospital stay was 13.5 days. There were no intra- and postoperative complications, no conversion to open surgery, and no recurrence after surgery. No patients died of gastric cancer during a median follow-up of 60.3 months (range, 38-84). Laparoscopic management for residual lesions of early gastric cancer after EMR is a safe, effective, and minimally invasive procedure by which curative resection can be expected.

Adenocarcinoma↗

A novel diagnostic method for evaluation of vascular lesions in the digestive tract using infrared fluorescence endoscopy.

BACKGROUND AND STUDY AIMS: We have developed an infrared fluorescence endoscope to evaluate gastrointestinal vascular lesions. Infrared endoscopy (IRE) after intravenous administration of indocyanine green (ICG) is used at present to examine vascular lesions such as esophageal varices. However, no previous study has compared the sensitivity of infrared fluorescence endoscopy (IRFE) with that of IRE. In this study, we compared the usefulness of IRFE and IRE. PATIENTS AND METHODS: For IRFE we used an infrared endoscope equipped with excitation and barrier filters and an intensified charge-coupled device camera. In preliminary experiments, the observable tissue depth was assessed by wrapping increasing numbers of layers of commercially available pork around a syringe containing a uniform concentration of ICG or by changing the concentration of ICG in a syringe covered by a piece of pork of uniform thickness. In the clinical part of the study, ICG was administered intravenously at different concentrations to patients with esophageal varices and the resulting infrared fluorescent images were evaluated. RESULTS: The preliminary experiments revealed that the depth of tissue that could be visualized was significantly greater in IRFE than it was in IRE (11.2 mm in IRFE vs. approximately 3.2 mm in IRE). Clear infrared fluorescence was obtained by IRFE at lower concentrations of ICG than the concentrations required to obtain clear images using IRE. In the clinical part of the study, clear infrared fluorescence was observed in a region where esophageal varices had been detected by conventional endoscopy when ICG was administered in doses of 0.005 mg/kg to 0.01 mg/kg, which was lower than the doses used in IRE. CONCLUSIONS: Compared with conventional IRE, IRFE facilitated the observation of deeper layers, and esophageal varices were observed by IRFE following the intravenous administration of a markedly reduced dose of ICG. IRFE, in combining the characteristics of reflected infrared light and fluorescence, may be a useful novel procedure in the diagnosis of vascular lesions in the gastrointestinal tract.

Aged↗

A survey of ammonia-assimilating micro-organisms in cattle manure composting.

AIMS: To evaluate the ammonia-assimilating abilities of micro-organisms isolated from cattle manure composting processes and to determine the distribution of cultivable species of ammonia-assimilating micro-organisms in microbial communities during the composting processes. METHODS AND RESULTS: Compost samples were collected from four stages of treatment. Trypto soya agar was used for the isolation of ammonia-assimilating aerobes. Many of the isolates showed high ammonia-assimilating ability in a medium containing basal components and a compost extract. Partial 16S ribosomal DNA sequencing showed that the cultivable species of highly efficient ammonia-assimilating isolates changed during the composting process. The community structure of micro-organisms and actinomycetes was analysed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). Two species of actinomycetes identified by PCR-DGGE coincided with those found among the cultured isolates. CONCLUSIONS: Ammonia-assimilating micro-organisms obtained by the cultivation method were not predominant in the microbial community during the composting process: however certain cultured actinomycetes were members of predominant species in the actinomycetes community. SIGNIFICANCE AND IMPACT OF THE STUDY: Ammonia assimilation by micro-organisms is one of the important mechanisms for ammonia retention in the composting process. Cultivable actinomycetes are a means for preventing ammonia emission from the composting process.

Actinomyces↗

Biomechanical properties of heat-treated bone grafts.

INTRODUCTION: A possible critical complication associated with banking bone is human immunodeficiency virus (HIV) infection. Recently, since the report of HIV infection in bone allografts from an HIV-seronegative donor, a more reliable method of sterilization for preserved bone graft has become necessary. Heat treatment of banking bone is one of the simple sterilization methods. This method is especially safe and practical for the prevention of HIV infection. MATERIALS AND METHODS: We previously reported a biological study on heat-treated bone graft. In that study, we showed that revascularization and new bone formation of bone graft after heat treatment at 60 degrees C was nearly the same as that of non-heat-treated bone graft, while at 100 degrees C, revascularization and new bone formation showed a significant delay. This time, we examined the change of mechanical strength of heat-treated bone grafts after transplantation in an experiment. To eliminate the problem of antigenicity of grafted bone, we used autografts, not allografts. Two types of heat-treated autografts were employed: heat-treated at 60 degrees C for 30 min and heat-treated at 100 degrees C for 5 min; as a control, fresh autografts were replaced in the left femur of rabbits. A strength test was performed for both the transplanted bone and the untreated intact right femur with time after transplantation. The strength test consisted of a compression test and torsional test, and the strength was compared between transplanted bone and the untreated intact right femur. RESULTS: In the compression test, the grafts heat-treated at 60 degrees C showed a strength ratio before transplantation of 97.3%. The strength ratio decreased to 63.5% at 18 weeks after transplantation. Then the strength ratio increased and recovered to 94.5% at 48 weeks after transplantation. However, the grafts heat-treated at 100 degrees C showed unsatisfactory mechanical strength, at 48 weeks the strength ratio was 60.1%, which was significantly lower compared with controls. In the torsional test, the grafts heat-treated at 60 degrees C showed almost the same strength observed in the compression test. However, the grafts heat-treated at 100 degrees C showed unsatisfactory mechanical strength: at 48 weeks, the strength ratio was 57.3%. CONCLUSION: Therefore, heat treatment at 60 degrees C is a useful sterilization method, not only in biological but also mechanical terms.

Animals↗

Hand-assisted laparoscopic splenectomy for solitary splenic metastasis from uterine corpus carcinoma.

Solitary splenic metastasis is a rare condition. We performed hand-assisted laparoscopic splenectomy (HALS) for a solitary splenic metastasis from a uterine corpus carcinoma that had directly invaded the wall of the stomach. HALS is a superior technique that offers the advantages of both open and laparoscopic splenectomy, and it may become one of the options for the management of primary and secondary cancer of the spleen.

Adenocarcinoma↗

Potential impact of orthotic gait exercise on natural killer cell activities in thoracic level of spinal cord-injured patients.

STUDY DESIGN: Prospective before-after trial. OBJECTIVE: To examine the changes of natural killer (NK) cell activity in response to orthotic gait exercise in thoracic level of spinal cord-injured (SCI) patients. SETTING: National Rehabilitation Center for Persons with Disabilities, Japan. METHODS: In all, 10 thoracic level of SCI patients (ranging Th5-Th12), who experienced orthotic gait training, participated in this study. NK cell activity at an effector:target (E/T) ratio (20:1) was examined in a sample of peripheral blood taken before and just after orthotic gait exercise for 20 min. On a separate day, to evaluate the physical intensity of the orthotic gait exercise, cardiorespiratory responses at rest and during exercise were measured. RESULTS: The resting value of the NK cell activity in our SCI patients was remarkably lower than that in normal subjects reported in previous studies. The NK cell activity was significantly increased through a 20 min orthotic gait exercise (pre versus post; 12.7+/-5.28 versus 17.76+/-6.71, P<0.05). The steady-state value of oxygen (VO2) and heart rate (HR) were 18.13+/-3.92 ml/kg and 142.53+/-19.84 b/min, respectively. It was noteworthy that a patient who showed decrement of NK cell activity in response to exercise had the highest level of injury (Th5), and showed the higher energy cost of orthotic gait. CONCLUSION: These findings suggested that the orthotic gait exercise has the potential to enhance the immune function for SCI persons, although patients with a higher level of SCI may have some difficulties. SPONSORSHIP: Mitsui Sumitomo Insurance Welfare Foundation

Adult↗

Stretch reflex excitability of the anti-gravity ankle extensor muscle in elderly humans.

AIM: To examine whether the stretch reflex excitability of the soleus muscle changes with age, stretch reflexes at rest (REST) and during weak voluntary contractions (ACT) were elicited in 18 older and 14 younger subjects. METHOD: The amplitude of the stretch reflex responses and gain, defined as the gradient of the regression line for the relation between stretch reflex responses against the angular velocity of the applied perturbation, were evaluated in each short-latency (M1) and two long-latency components (M2 and M3). RESULTS: It was found that in the older group, both the amplitude and gain of the M1 component did not change from the REST to the ACT conditions, whereas in the younger group both variables significantly increased from the REST to ACT conditions. The latency of the M1 component was significantly shorter under the REST condition (older vs. younger: 51.8 +/- 7.37 vs. 55.1 +/- 8.69 ms), while no group differences were found in those variables under the ACT condition, suggesting that the muscle-tendon complexes of SOL muscles of the older subjects were less elastic and had less slack, probably due to age-related histochemical alterations. Further, the Hoffman reflex (H-reflex), elicited during the REST condition in 10 older and 11 younger subjects showed no significant differences, suggesting that the soleus motoneuron response to the Ia input was comparable between the two subject groups. CONCLUSION: The histochemical alterations occurring with the ageing process might augment the short-latency stretch reflex in the SOL muscle without enhancement of motoneuronal excitability, and this effect might be masked when the muscle is voluntarily activated.

Adult↗

Effects of acute moderate exercise on the phagocytosis of Kupffer cells in rats.

AIM: This study investigated the function of Kupffer cells, and particularly their role as immunocompetent cells that come into contact with gut-derived endotoxin, in the acute exercise of rats. METHODS: Female Fischer 344 rats were run on a treadmill at 21 m min(-1) for 60 min on a 15% grade. RESULTS: Afterwards, the number of latex particles in the liver was higher in the exercising rats than that in resting rats and an increase in the number of latex particles phagocytosed by each Kupffer cell was noted. The plasma endotoxin concentration was significantly higher in the exercise group than in the resting rats, and the small intestine was damaged by the exercise. Plasma corticosterone and thyroxine 4 levels were unchanged. Although the number of Kupffer cells was unchanged by acute exercise, the number of CD14-positive Kupffer cells increased. Plasma liver enzyme activities were slightly increased by acute exercise, whereas plasma tumour necrosis factor-alpha was not detected. CONCLUSION: These results suggest that moderately intense exercise increases the phagocytosis of Kupffer cells, and that it might be induced by endotoxemia of portal blood caused by intestinal mucosal lesions resulting from acute exercise.

Animals↗

Discrepancy between lesion distributions on methionine PET and MR images in patients with glioblastoma multiforme: insight from a PET and MR fusion image study.

OBJECTIVE: To examine (11)C-methyl methionine (MET) accumulation on positron emission tomographic (PET) imaging of glioblastoma multiforme to determine the distribution of metabolic abnormality compared with magnetic resonance imaging (MRI). METHODS: Contemporaneous MRI was superimposed on corresponding MET-PET images in 10 patients with newly diagnosed glioblastoma multiforme before treatment. Differences between the extended area of MET accumulation on PET imaging (MET area), the gadolinium (Gd) enhanced area on T1 weighted images (Gd area), and the abnormal high signal intensity area on T2 weighted images (T2-high area) were assessed. RESULTS: The MET area was larger than the Gd area and included the entire Gd area. The discrepancy in volume between the MET and Gd areas became greater with increasing tumour diameter. On average, 58.6% of the MET area was located within the Gd area, 90.1% within 10 mm outside the Gd area, 98.1% within 20 mm, and 99.8% within 30 mm. A newly developed Gd area had emerged in five of the 10 cases up to the time of study. In three of the five cases this was in the MET area even after complete surgical resection of the Gd area on the initial MRI; in the remaining two it originated in the residual Gd area after surgery. In all cases, the T2-high area was larger than the MET area. The MET area extended partly beyond the T2-high area in nine cases, and was completely within it in one. CONCLUSIONS: Glioblastoma multiforme cells may extend over the Gd area and more widely with increasing tumour size on Gd-MRI. The T2-high area includes the greater part of the tumour but not its entire area. The methods reported may be useful in planning surgical resection, biopsy, or radiosurgery.

Adult↗

Stable transformation of rice (Oryza sativa L.) via microprojectile bombardment of highly regenerative, green tissues derived from mature seed.

A highly efficient and reproducible transformation system for rice ( Oryza sativa L. cv. Taipei 309) was developed using microprojectile bombardment of highly regenerative, green tissues. These tissues were induced from mature seeds on NB-based medium containing 2,4-dichlorophenoxyacetic acid (2,4-D), 6-benzylaminopurine (BAP) and high concentrations of cupric sulfate under dim light conditions; germinating shoots and roots were completely removed. Highly regenerative, green tissues were proliferated on the same medium and used as transformation targets. From 431 explants bombarded with transgenes [i.e. a hygromycin phosphotransferase ( hpt) gene plus one of a wheat thioredoxin h ( wtrxh), a barley NADP-thioredoxin reductase ( bntr), a maize Mutator transposable element ( mudrB) or beta-glucuronidase ( uidA; gus) gene], 28 independent transgenic events were obtained after an 8- to 12-week selection period, giving a 6.5% transformation frequency. Of the 28 independent events, 17 (61%) were regenerable. Co-transformation of the second introduced transgene was detected in 81% of the transgenic lines tested. Stable integration and expression of the foreign genes in T(0) plants and T(1) progeny were confirmed by DNA hybridization, western blot analyses and germination tests.

Base Sequence↗

Chromosomal imbalances associated with acquired resistance to fluoropyrimidines in human colorectal cancer cells.

The chromosomal aberrations underlying the development of resistance to fluoropyrimidines have not yet been identified. To characterise the genomic changes that induce the development of resistance to fluoropyrimidines, we used comparative genomic hybridisation (CGH) to analyse and compare the parent DLD-1 human colorectal cancer cell line and two cell lines, DLD-1/5-FU and DLD-1/FdUrd, which were resistant to 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd), respectively. Both resistant cell lines showed a genetic aberration derived from the parental cell line DLD-1. Losses of 3p and 3q were also detected as additional genetic changes in the two resistant cell lines. Both resistant cell lines showed decreased orotate phosphoribosyltransferase (OPRT) activity, which is associated with the activity of the uridine monophosphate (UMP) synthase gene (3q13). These results suggested that the loss of 3q might be a genetic change responsible for the decreased OPRT activity and fluoropyrimidine cytotoxic response in cancer cells. Amplification of 18p11.2-p11.3 containing the thymidine synthase (TS) gene (18p11.32) was observed only in the DLD-1/FdUrd-resistant cell line, which overexpresses TS. These findings suggested that 18p amplification represents a genetic change associated with the overexpression of the TS protein. Our results indicate that chromosomal aberrations identified by CGH could explain, at least in part, acquired fluoropyrimidine resistance.

Antimetabolites, Antineoplastic↗