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Biomedical subjects

M Terada

Publications and source records attributed to M Terada.

At least 37 records · Page 2Linked to original sources

Development of spectral colour banding in cytogenetic analysis.

We developed a novel chromosome banding technique-spectral colour banding (SCAN). With this technique we displayed a multicolour banding pattern that almost entirely correlated with the corresponding G-banding pattern. With SCAN analysis we could identify the chromosome-band origin of double minute chromosomes in gastric cancer. Our preliminary use of this technique suggests that it has significant clinical applications for cytogenetic analysis.

Carcinoma, Signet Ring Cell↗

Absence of endothelial cells, central necrosis, and fibrosis are associated with aggressive inflammatory breast cancer.

We recently established a new human inflammatory breast cancer (IBC) xenograft (WIBC-9) originating from a patient with IBC. The graft was transplantable in BALB/c nude and severe combined immunodeficient (SCID) mice. WIBC-9 was frequently accompanied by lung metastasis and exhibited erythema of the overlying skin, reflecting its human counterpart. Histological study of the original tumor and WIBC-9 revealed invasive ductal carcinoma with a hypervascular structure of solid nests and marked lymphatic permeation in the overlying dermis. In the central part of the solid nests, absence of endothelial cells, central necrosis, and fibrosis were observed. In vitro, WIBC-9 formed tube-like structures and loops, reflecting its in vivo feature and its human counterpart. WIBC-9 exhibited aneuploidy, ErbB-2 gene amplification, and an absence of estrogen receptor and progesterone receptor, which is consistent with IBC. Comparative studies of WIBC-9, three established non-IBC xenografts, and a human breast cancer cell line (SK-BR3) by reverse transcription-PCR, ELISA, and immunohistochemistry indicated that certain human genes (interleukin 8, vascular epidermal growth factor, basic fibroblast growth factor, angiopoietin 13, Flt-1, Tie-2, and Tie-1) and certain murine genes (integrin alpha(v)beta3, flt-1, tie-2, vascular epidermal growth factor, and CD31) were overexpressed in exposure to tumor cells. The molecular basis and these unique histological features may be associated with aggressive IBC on angiogenic and nonangiogenic pathways.

Angiogenesis Inducing Agents↗

Tetranuclear titanium 7,7'-modified binaphtholate cluster as a novel chiral Lewis acid catalyst.

Chiral tetranuclear Ti cluster, a cubic structure constituted of four Ti atoms and OHs, and six (R)-binaphthols (BINOL) bridged two Ti atoms as ligands, is shown to be a novel chiral Lewis acid catalyst for the [2+3] cycloaddition reaction with nitrones. The chiral Ti clusters with 7,7'-substituted (R)-BINOL ligands was synthesized to give enhanced enantiomeric excesses up to 78% ee.

Journal Article↗

Fibroblast growth factor receptor 3 lacking the Ig IIIb and transmembrane domains secreted from human squamous cell carcinoma DJM-1 binds to FGFs.

The fibroblast growth factor receptors (FGFRs) are a family of transmembrane tyrosine kinases that play a key role in cell growth and tumorigenesis in response to FGFs. FGFR complexity is increased by the existence of additional isoforms generated by alternative mRNA splicing. We identified that the transcript FGFR3DeltaTM, an alternatively spliced isoform of FGFR3 lacking exons encoding the C-terminal half of Ig III (IIIb) and transmembrane domains, is expressed in the human squamous carcinoma cell line DJM-1. To determine whether FGFR3DeltaTM has the potential to be secreted, we analyzed the protein expression in CHOK1 cells transfected with FGFR3DeltaTM cDNA and DJM-1 cells. Western blot analysis revealed that FGFR3DeltaTM protein was secreted, N-glycosylated, and dimerized by an intermolecular disulfide bond. Cross-linking experiments showed that FGF1 and FGF2 were able to bind to FGFR3DeltaTM, suggesting that the loss of the Ig IIIb domain may confer upon FGFR3DeltaTM the ability to bind to FGF2.

Alternative Splicing↗

Suppression of colorectal cancer growth using an adenovirus vector expressing an antisense K-ras RNA.

In human colorectal cancer, K-ras point mutations occur in approximately 40-50% of the cases, a frequency second only to pancreatic cancer (80-90%). Unlike pancreatic and lung cancers, however, the tumor-suppressive effect of antisense K-ras RNA expression has not been examined for colorectal cancers. A recombinant adenovirus vector expressing an antisense or sense K-ras gene fragment (AxCA-AS-K-ras or AxCA-S-K-ras) was first transduced into seven human colorectal cancer cell lines. Stable expression of antisense or sense K-ras RNA was detected by RNA blot analysis. Western blot analysis confirmed a reduction of up to 25% of K-ras-specific p21 protein in the antisense K-ras-transduced HCT-15 cells. In contrast to our previous findings on pancreatic cancer, the status of K-ras point mutations was not correlated with the growth-suppressive effect of the antisense K-ras vector: both the K-ras-mutation-positive and -negative colorectal cancer cell lines were suppressed for their growth in vitro. There was no growth-inhibitory effect on normal cells such as hepatocytes. Next, to test the efficacy in vivo, HCT-15 cells were inoculated subcutaneously into the left flank of SCID mice, and AxCA-AS-K-ras was injected intratumorally three times after the tumor mass was established. The infection of AxCA-AS-K-ras, but not the control AxCA-S-K-ras, significantly suppressed the growth of the HCT-15 subcutaneous tumor. This study shows that the adenovirus-mediated in vivo gene transfer of the antisense K-ras construct may be a useful therapeutic strategy for colorectal cancer.

Adenoviridae↗

Reoperative coronary artery bypass grafting via a left thoracotomy and a small laparotomy without cardiopulmonary bypass: report of a case.

A 66-year-old woman with aortic stenosis underwent an aortic root replacement with a composite graft and coronary artery reconstruction 2 years before presentation. On coronary angiography performed 2 years after operation, saphenous vein graft (SVG) to right coronary artery and SVG to first diagonal branch had both become totally occluded. SVG to left anterior descending artery showed 75% stenosis on the heel side of the distal anastomosis. The patient underwent a second coronary artery bypass via a left thoracotomy (the left internal thoracic artery was anastomosed to the first diagonal branch by interposing it with the left radial artery) and a small laparotomy (the right gastroepiploic artery was anastomosed to the right coronary artery) without a cardiopulmonary bypass. This approach is preferable to avoiding both a resternotomy and cardiopulmonary bypass in patients requiring repeat surgery.

Aged↗

A potent antimalarial activity of Hydrangea macrophylla var. Otaksa leaf extract against Plasmodium yoelii 17XL in mice.

The antimalarial activity of the hot-water extract of Hydrangea macrophylla var. Otaksa leaves was evaluated against Plasmodium yoelii 17XL in mice. Non-treated control mice died from 6 to 7 days after infection, but mice treated with the leaf extract survived during the experiment. Mice given the extract orally showed low parasitemia levels during administration. Following a transient recrudescence of malaria parasites in the bloodstream of treated mice, no parasites could be detected by a microscopic examination. Furthermore, the 30% MeOH aq. eluate and 50% MeOH aq. eluate from dried leaves of H. macrophylla var. Otaksa showed an antimalarial activity in vivo. Sulfamonomethoxine was orally given to infected mice to compare with the antimalarial activity of the hot-water extract of leaves. Sulfamonomethoxine given orally reduced parasitemia, but no complete cure of mice was observed.

Animals↗

Japanese experience of telemedicine in oncology.

We started telemedicine projects from 1990 with a telepathology system within Tsukiji Campus of National Cancer Center. In 1994, we connected Tsukiji Campus and Kashiwa Campus by 6 Mbps optical fiber leased line using IP protocol for data transmission, for teleconference, telepathology, and teleradiology projects. We also started connection of regional cancer centers and are now forming a cancer center network of 14 cancer centers. We are at present organizing 130 teleconferences per year with an attendance of more than 16000 people as summary. We have also used a high-resolution image transferring system, such as SHD (2000 pixelsx2000 pixels resolution) system on one side, and an economical telemedicine system using JAVA and a WWW browser (NCC_image) on the other side. We think that providing information is another field of telemedicine. We began the experimental gopher and WWW service in 1993. We are now providing official up-to-date cancer information for patients and healthcare professionals. We are getting more than 400000 hits per month. We are also providing a teleconference video session which is held every week on the Internet using a Real Video system with synchronized slide presentation on the WWW browser. We are also organizing a Cancer Image Reference Database System including DICOM images with viewer software. This paper is a summary of the telemedicine projects performed at the National Cancer Center.

Community Networks↗

Polyethylenimine-mediated gene transfer into pancreatic tumor dissemination in the murine peritoneal cavity.

Although peritoneal dissemination of cancer cells often occurs at the advanced stages of pancreatic, gastric or ovarian cancers, no effective therapy has been established. Cationic lipid-mediated gene transfer into peritoneal dissemination may offer a prospect of safe therapies, but vector improvements are needed with regard to the efficiency and specificity of the gene transfer. In this study, the intraperitoneal injection of plasmid DNA:polyethylenimine (PEI) complexes into mice was evaluated as a gene delivery system for the peritoneal disseminations. The luciferase and beta-galactosidase genes were used as marker genes. PEI was more efficient than the cationic lipids examined in this study in vivo, and the transgene was preferentially expressed in the tumors. Although PCR analysis showed that the injected DNA was delivered to various organs, the distributed DNA became undetectable by 6 months after the gene transfer. Blood chemistry and histological analysis showed no significant toxicity in the injected mice. This study demonstrated that the intraperitoneal injection of DNA:PEI is a promising delivery method to transduce a gene into disseminated cancer nodules in the peritoneal cavity.

Animals↗

Expression of Rho-family GTPases (Rac, cdc42, RhoA) and their association with p-21 activated kinase in adult rat peripheral nerve.

To clarify the presence of the Rho family of small GTPases p21-activated kinase (pak) signaling pathway in the PNS, we have examined their expression, the association between the small GTPases and pak and the pak kinase activity in the PNS using immunoblot analysis, immunohistochemistry, co-immunoprecipitation study, and in vitro kinase assay. Immunoblot analysis showed the expression of Rac, cdc42, RhoA and pak in the dorsal root ganglion (DRG) and sciatic nerve. The localization of these proteins in the DRG neurons and axons and Schwann cells of the sciatic nerve was confirmed by immunohistochemistry. Co-immunoprecipitation studies indicated the in vivo associations of pak with Rac and cdc42, but not with RhoA, in both the DRG and sciatic nerve. The autophosphorylation of pak and phosphorylation of histone H4 by pak were also found in the DRG and sciatic nerve as well as in the CNS. These results suggest that the Rac/cdc42-pak signaling pathway exists and functions in the PNS and may mediate some intracellular signals.

Animals↗

Mechanism of inhibitory effect of NCC164 on replication of human immunodeficiency virus.

The effect of a novel anti-HIV (human immunodeficiency virus) compound, designated NCC164, has been studied with HIV infected cultures. The agent exhibited concentration-dependent inhibition of HIV replication in primary infected cultures of H9 cell line and PBMCs. Substantial inhibition of viral replication was observed at concentration of NCC164 that showed little cytotoxicity. The ratio of IC50 values for the MTT (3-4,5 dimethylthiazol-2,5 diphenyl tetrazolium bromide) to RT (reverse transcriptase) assays means the selectivity index was more than 100. In attempting to define the inhibitory mechanism of NCC164, we investigated its effect on each step of HIV replication. This agent was highly effective against HIV replication regardless of the addition period during early stages of infection (adsorption to integration) but did not inhibit reverse transcriptase activity directly. The agent efficiently blocked virus maturation without side effect and the number of progeny produced by NCC164-treated cells was markedly reduced.

Adenosine↗

Efficient gene transduction by RGD-fiber modified recombinant adenovirus into dendritic cells.

Dendritic cells (DC) are important antigen-presenting cells in the development of an anti-tumor T cell response. To extend the range of current immuno / gene therapies, we tested luciferase-expressing RGD-adenovirus (Ad) (Ad5lucRGD)-mediated transduction into DC. Phenotypically characterized DC were generated from peripheral blood CD14(+) cells by incubation with granulocyte-macrophage colony-stimulating factor, interleukin-4 and tumor necrosis factor alpha. On the 7th day of culture, the cells became mature DC with a CD1a(+), CD11c(+), CD80(+), CD83(+), CD86(+), human leukocyte antigen (HLA)-DR(+), CD14- phenotype. The expression of alpha( v)beta(3) integrin was enhanced on day 3 and returned to the basal level on day 7. We then compared the transduction efficiency of an Ad5lucRGD system to that using conventional Ad, in cells harvested on days 1, 3 and 7 of culture. Luciferase activity was negligible in AdCMVLuc, but remarkable in cells processed with Ad5lucRGD. Activity was maximal in cells that had been cultured for 3 days. Recombinant Ad5 fiber knob protein blocked AdCMVLuc- and Ad5lucRGD-mediated gene transduction by 90% and 20%, respectively. Surface markers and cytokine production were not affected by Ad5lucRGD-mediated transduction.

Adenoviridae↗

Hepatocellular carcinoma: involvement of the internal mammary artery.

PURPOSE: To investigate factors related to the development of internal mammary arteries (IMAs) as feeding arteries of hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: In 30 patients with HCC located in ventral hepatic areas directly beneath the diaphragm, bilateral internal mammary arteriography was performed to explore involvement of the IMA with HCC. The number of previous transcatheter arterial embolizations (TAEs), tumor size, time from initial TAE to IMA angiography, inferior phrenic artery (IPA) involvement with tumor, presence of hepatic artery occlusion, and use of other treatments were compared in groups with and without involvement of the IMA. RESULTS: The group with IMA involvement included 10 patients; the group without involvement, 20 patients. TAE had been performed two to 12 times in the group with involvement and zero to six times in the group without involvement (P =.01). Mean tumor sizes in these two groups were 5.1 and 6.0 cm, respectively; hepatic artery occlusion was noted in nine and zero patients (P =.01) in the two groups. The time from initial TAE to IMA angiography ranged from 3 to 53 months (median, 31.5 months) and from zero to 89 months (median, 0 months) (P =.01). IPA involvement was observed in seven and four patients (P =.015). CONCLUSION: These results strongly suggest that, regardless of tumor size, when HCCs are located in the ventral hepatic areas directly beneath the diaphragm, the IMAs serve as feeding arteries in patients with hepatic artery occlusion caused by repeated TAE.

Aged↗

Multiple logistic regression analysis of risk factors for the development of steroid-dependent asthma in the elderly: a comparison with younger asthmatics.

BACKGROUND: The percentage of the aged among all patients with bronchial asthma is increasing. OBJECTIVE: To investigate the risk factors for the development of steroid-dependent asthma in the elderly. METHODS: A multiple logistic regression analysis involving various clinical factors between steroid-dependent and -independent asthma was carried out for 59 asthmatics aged over 60 years, including 16 patients with steroid-dependent asthma. The calculated risk for each factor was compared with that obtained from 122 younger asthmatics aged 20-59 years. RESULTS: Among the factors examined (sex, age, period from onset of asthma, type of asthma and family history of asthma, plus history of smoking, atopic dermatitis, allergic rhinitis, chronic sinusitis and nasal polyps), the significant risk factors for the development of steroid dependency in the elderly asthmatics were only family history of bronchial asthma (relative risk 3.6) and smoking history (relative risk 6.9). CONCLUSIONS: Some risk factors for steroid-dependent asthma in younger individuals were not significant in the elderly. Since the smoking history was most closely associated with the development of steroid dependency in the elderly, even though most of them had quit smoking, it is important for patients with asthma to avoid smoking.

Adult↗

Biomaterials for gene delivery: atelocollagen-mediated controlled release of molecular medicines.

Over the last decade, increasing attention has been paid to the development of systems to deliver drugs for long periods at controlled rates. Some of these systems can deliver drugs continuously for over one year. However, little effort has been given to developing systems for the controlled release of nucleic acids. Recently, a novel gene transfer method which allows prolonged release and expression of plasmid DNA in vivo in normal adult animals was established. In this system, a biocompatible natural polymer such as collagen or its derivatives acts as the carrier for the delivery of DNA vectors. The biomaterial carrying the plasmid DNA was administered into animals and, once introduced, gradually released plasmid DNA in vivo. A single injection of plasmid DNA/biomaterial produced physiologically significant levels of gene-encoding proteins in the local/systemic circulation of animals and resulted in prolonged biological effects. These results suggest that the biomaterials carrying plasmid DNA may enhance the clinical potency of plasmid-based gene transfer, facilitating a more effective and long-term use of naked plasmid vectors for gene therapy. Furthermore, the biomaterials can be removed surgically, minimizing the effect of gene products if some unexpected side effects should be observed after application. The application of these systems to expand the bioavailability of molecular medicine, including antisense oligonucleotides and adenovirus vectors, and to aid in stem cell transplantation in the context of DNA-based tissue engineering will be discussed.

Adenoviridae↗

Establishing joint visual attention and pointing in autistic children with no functional language.

Joint visual attention is defined as looking where someone else is looking. The purpose of this study was to examine the conditions for establishing joint visual attention in autistic children who have no functional speech. An experimenter, sitting facing the child, looked at one of six pictures near the child. Analysis showed that joint visual attention to stimuli behind the child and therefore outside of the visual field occurred at a higher rate when the visual angle between the stimuli was about 60 degrees. Spontaneous pointing at the target object increased with training which included feedback and physical guidance. These results are discussed in terms of the effects of environmental variables and perceptual mechanisms on the emergence of joint visual attention in autistic children. The possibility of using an adult's social cues and expanding the child's visual field as a remedial procedure is also addressed.

Attention↗

Pesticide poisoning initially suspected as a natural death.

A pesticide poisoning victim suspected initially as having died a natural death was autopsied. The victim was a 47-year-old male. Macroscopically, signs of acute death and, in particular, general erosion in the mucosa of the airways and esophagus were observed. In the gastric contents, which had a pungent smell and a greenish-brown color, 5.00 g/L of propanil, 1.27 g/L of carbaryl, 0.38 g/L of ethylbenzene, and 0.32 g/L of xylene were detected. In the blood (serum), 21.6 mg/L of propanil, 8.1 mg/L of carbaryl, 1.7 mg/L of ethylbenzene, and 4.0 mg/L of xylene were identified. Postmortem methemoglobinemia (45%) was recognized. The cause of death was considered to have been pesticide poisoning; propanil was probably most responsible for his death. The police considered the case to be "death with illness as the suspected cause." By performing an autopsy, however, we were able to clarify that the cause of death was pesticide poisoning.

Carbaryl↗