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Biomedical subjects

Jun Yoshida

Publications and source records attributed to Jun Yoshida.

At least 19 recordsLinked to original sources
PubMed2007

Linkage effects of chromium(III) acetylacetonato units on chiral induction of liquid crystal phases.

The linkage effects of polynuclear metal complexes on chiral induction have been studied by application of the chiral oligomers of acetylacetonato chromium(III) units as a dopant, inducing chiral nematic phases. The compounds were prepared by reacting [Cr(acac)(3)] (acac = acetylacetonato) and 1,1,2,2-tetraacetylethane (taetH(2)) in solid phase at 160 degrees C. Binuclear diastereomers were separated on a silica gel column, followed by chromatographic resolution on a chiral column packed with an ion-exchange adduct of Delta-[Ru(phen)(3)](2+) (phen = 1,10-phenanthroline) and synthetic hectorite. An enantiomeric pair (DeltaDelta- and LambdaLambda-[Cr(acac)(2)(taet)Cr-(acac)(2)]) and a meso species (DeltaLambda-[Cr(acac)(2)(taet)Cr(acac)(2)]) were identified. The binuclear enantiomers were doped into a room-temperature nematic liquid crystal, N-methoxybenzylidene-4-n-butylaniline. Helical twisting power (beta(M)) was found to be +97.9 and -88.9 microm(-1) for LambdaLambda- and DeltaDelta-[Cr(acac)(2)(taet)Cr(acac)(2)], respectively. The values were compared with beta(M) for the monomeric enantiomers (+99.5 and -91.0 microm(-1) for Lambda- and Delta-[Cr(acac)(3)], respectively). The results are interpreted on the basis of the surface chirality model. DeltaDelta-[Cr(acac)(2)(taet)Cr(acac)(2)] was found to photoisomerize both in a hexane solution and in a liquid crystal phase of ZLI-1132. The quantum yield of photoisomerization in a liquid crystal phase was lowered to ca. 30% of that in a hexane solution.

Journal Article↗
PubMed2006

Electron transfer through clay monolayer films fabricated by the Langmuir-Blodgett technique.

Hybrid films composed of amphiphilic molecules and clay particles were constructed by the modified Langmuir-Blodgett (LB) method. Clays used were sodium montmorillonite (denoted as mont) and synthetic smectite containing Co(II) ions in the octahedral sites (denoted as Co). Two kinds of amphiphilic molecules were used-[Ru(dC(18)bpy)(phen)2](ClO4)2 (dC(18)bpy = 4,4'-dioctadecyl-2,2'-bipyridyl and phen = 1,10-phenanthroline) (denoted as Ru) and octadecylammonium choloride (ODAH+Cl- or denoted as ODAH). Three kinds of hybrid films (denoted as Ru-mont, Ru-Co, and ODAH-Co films) were prepared by spreading an amphiphilic molecule onto an aqueous suspension of a clay. Atomic force microscopy (AFM) analyses of the films deposited on silicon wafers indicated that closely packed films were obtained at 20 ppm for all the above three cases. Cyclic voltammetry (CV) was measured on an ITO electrode modified with a hybrid film or a monolayer film of pure Ru(II) complex salt (denoted as Ru film). The Ru(II) complexes incorporated in the Ru-mont film lost their redox activity, indicating that montmorillonite layers acted as a barrier against electron transfer. In contrast, the same complexes in the Ru-Co film were electrochemically active with the simultaneous appearance of the redox peaks due to the Co(II)/Co(III) (or Co(II)/Co(IV)) couple. The results implied that electron transfer through cobalt clay layers was possible via mediation by Co(II) ions in a clay sheet. For an aqueous solution containing nitrite ions (NO2-) at pH 3.0, a large catalytic oxidation current was observed for both the electrodes modified with the Ru-mont and Ru-Co films. The results were interpreted in terms of the mechanisms that the charge separation of an incorporated Ru(II) complex took place to produce a pair of a Ru(III) complex and an electron and that the generated Ru(III) complex was reduced by a nitrite ion before it recombined with the electron.

Journal Article↗
PubMed2006

Prediction of rebleeding from angiographic features in vertebral artery dissecting aneurysms.

To identify patient characteristics and angiographic features that predict high risk for rebleeding in vertebral artery (VA) dissecting aneurysms. We analyzed 62 patients treated for subarachnoid hemorrhage (SAH) from VA dissecting aneurysms (male: female, 46:16; mean age, 51.7 +/- 8 years). Univariate and multivariate stepwise logistic regression analyses were performed to assess relationships between rebleeding rate and age, gender, history of hypertension, sidedness of the aneurysm, angiographic configuration, and location relative to the origin of the posterior inferior cerebellar artery (PICA). Rebleeding occurred in 22 patients (37%), mostly within 24 h. Patients without rebleeding had favorable outcomes, while patients with rebleeding showed higher mortality. Angiographic patterns with high rebleeding rates included "stenosis and dilation" (50%), and "lateral protrusion" (43%), contrasting with "dilation and stenosis" (20%) and other types. Rebleeding also was likely in aneurysms proximal to or at the PICA origin (rate, 47% or 46%) than distal to the PICA origin (21%). Multivariate logistic regression analysis found two factors independently associated with rebleeding: angiographic pattern of the aneurysm (odds ratio 1.88:1, P=0.0366), and location relative to the PICA origin (odds ratio 4.93:1, P=0.028). High risk of rebleeding in VA dissecting aneurysms can be predicted by angiographic configurations such as "stenosis and dilation" and "lateral protrusion" and by location at or proximal to the PICA origin.

Adult↗
PubMed2006

Stereotactic radiosurgery as a salvage treatment for recurrent epipharyngeal carcinoma.

Fourteen patients with recurrent epipharyngeal carcinoma (EPC) were treated by gamma knife stereotactic radiosurgery. The tumor volume ranged from 0.3 to 80 ml (median 18.9 ml). Treatment was done with a tumor margin dose of 10-27 Gy (median 15 Gy). The median follow-up period was 15 months (range 2-47 months). Ten patients were alive and 4 were dead at the end of the follow-up period. In 6 patients (43%), the tumor disappeared or decreased in size until the end of the follow-up period. In 2 (14%), the tumor remained unchanged in size. In 6 (43%), the tumor showed regression initially but was enlarged later. A second radiosurgery was performed in 4 of those 6 cases and the tumor decreased in size again in 3 of them. Thus, the overall control rate of local tumor was 79% (11/14). In selected patients with recurrent EPC, stereotactic radiosurgery can be considered as a salvage treatment producing local control.

Adult↗
PubMed2006

Combination of in vivo angiopoietin-1 gene transfer and autologous bone marrow cell implantation for functional therapeutic angiogenesis.

OBJECTIVE: Autologous bone marrow mononuclear cell (BM-MNC) implantation into ischemic tissues promotes angiogenesis, but a large amount of marrow aspiration is required, which is a major clinical limitation. Angiopoietin-1 (Ang-1) is requisite for vascular maturation during angiogenesis. We examined the impacts of combinatorial Ang-1 gene transfer and low-dose autologous BM-MNC implantation on therapeutic angiogenesis in a rabbit model of hind limb ischemia. METHODS AND RESULTS: Rabbits were divided into 4 groups: phosphate-buffered saline (control), 500 microg Ang-1 plasmid (Ang-1), 1 x 10(6) autologous BM-MNCs (BMC), and Ang-1 plasmid plus BM-MNCs (combination). The Ang-1 group had a greater angiographic score and capillary density compared with the control (P<0.05), but the Ang-1 gene therapy alone did not improve transcutaneous oxygen pressure (TcO2) and skin ulcer score. However, the combination group showed a significant improvement in not only angiographic score and capillary density (P<0.05) but also TcO2 (P<0.05) and skin ulcer score. These efficacies were greater in the combination group compared with the BMC group. CONCLUSIONS: This Ang-1 gene and BM-MNC combination therapy enhances not only quantitative but also qualitative angiogenesis in ischemic tissues. Moreover, the combination therapy will enable a reduction in the amount of BM aspiration required for significant therapeutic angiogenesis.

Angiography↗
PubMed2006

EGFR mutations in patients with brain metastases from lung cancer: association with the efficacy of gefitinib.

Gefitinib--a specific inhibitor of epidermal growth factor receptor (EGFR)-associated tyrosine kinase--has demonstrated efficacy in a subgroup of patients with non-small-cell lung carcinoma (NSCLC) who fail conventional chemotherapy. It is also reported to have an antitumor effect in brain metastases from NSCLC. Additionally, EGFR mutations have shown a strong association with gefitinib sensitivity for NSCLC. Here, we assessed the efficacy of gefitinib in brain metastases from NSCLC and evaluated the association of this efficacy with EGFR mutations. We retrospectively reviewed eight cases in which patients were suffering from brain metastases before the initiation of gefitinib treatment. Brain tumor response could be evaluated by MRI in these patients; EGFR gene analyses were also available. We evaluated whether objective tumor response was observed after gefitinib treatment and assessed the efficacy of gefitinib as effective, noneffective, or not assessable in consideration of the influence of previous radiotherapy. Of the eight patients, the efficacy of gefitinib was assessed as effective in three and as noneffective in three. All three patients demonstrating effective efficacy had EGFR mutations in the tyrosine kinase domain (deletion mutation in two patients and point mutation in one patients), whereas none of the three patients demonstrating noneffective efficacy had EGFR mutations. Gefitinib appears to be effective in treating brain metastases in a subgroup of patients. Our data suggested a possible association between the efficacy of gefitinib in the treatment of brain metastases and EGFR mutations.

Adult↗
PubMed2006

Stereotactic radiosurgery as a salvage treatment for recurrent skull base adenoid cystic carcinoma.

Twelve patients (15 lesions) with recurrent skull base adenoid cystic carcinoma (ACC) were treated by Gamma Knife stereotactic radiosurgery (SRS). The tumor volume ranged from 2 to 103 ml (median 15 ml). Treatment was prescribed at the 40-60% isodose line and ranged from 10 to 18 Gy (median: 13.0 Gy). The median follow-up period was 18 months (range 3-55). Six patients were alive and 6 dead at the end of the follow-up period. Only 1 patient died from local tumor recurrence. Ten among 15 tumors treated by SRS decreased in size until the end of the follow-up period or the patients' death. Three remained unchanged in size. Two tumors initially regressed but then increased in size. In selected patients with recurrent skull base ACC, SRS can be considered as a salvage treatment with good local control.

Adolescent↗
PubMed2006

Activation of the JAK-STAT signaling pathway in the rat basilar artery after subarachnoid hemorrhage.

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) is one of the most important signaling pathways transducing signals from the cell surface in response to cytokines. Subarachnoid hemorrhage (SAH) produces cytokines in the CSF. We investigated whether this signaling pathway is activated in the rat basilar artery after SAH by cytokines. In a rat single-hemorrhage model of SAH, basilar arteries and CSF were obtained until 7 days after SAH. The concentration of interleukin-6 (IL-6) in CSF was measured by ELISA. Western blot analysis with JAK1, phosphospecific-JAK1, STAT3, phosphospecific STAT3 at Tyr705 and Ser727, cyclooxygenase-2 (COX-2), and actin antibodies was performed in basilar artery. The expressions of STAT3, phosphospecific STAT3 at Tyr705 and Ser727, and COX-2 in basilar artery were examined by immunohistochemical studies. The concentration of IL-6 immediately increased after SAH and Western blot analysis revealed that JAK1 was phosphorylated within 2 h, accompanied by phosphorylation of STAT3 at Tyr705, extending to Ser727 at days 1-2. Immunohistochemistry revealed phosphorylation of STAT3 to occur in endothelial and smooth muscle cells of the basilar artery. In addition, intracisternal injection of IL-6 by itself significantly increased phosphorylation of STAT3 at Tyr705 and Ser727. Expression of COX-2 was also upregulated in endothelial cells of the basilar artery. These results indicate that SAH produces the proinflammatory cytokine IL-6 in the CSF, which activates the JAK-STAT signaling pathway in the basilar artery and induces transcription of immediate early genes.

Animals↗
PubMed2006

Activation of JAK/STAT signalling in neurons following spinal cord injury in mice.

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway is one of the most important in transducing signals from the cell surface to the nucleus in response to cytokines. In the present study, we investigated chronological alteration and cellular location of JAK1, STAT3, phosphorylated (p)-Tyr1022/1023-JAK1, p-Tyr705-STAT3, and interleukin-6 (IL-6) following spinal cord injury (SCI) in mice. Western blot analysis showed JAK1 to be significantly phosphorylated at Tyr1022/1023 from 6 h after SCI, peaking at 12 h and gradually decreasing thereafter, accompanied by phosphorylation of STAT3 at Tyr705 with a similar time course. ELISA analysis showed the concentration of IL-6 in injured spinal cord to also significantly increase from 3 h after SCI, peaking at 12 h, then gradually decreasing. Immunohistochemistry revealed p-Tyr1022/1023-JAK1, p-Tyr705-STAT3, and IL-6 to be mainly expressed in neurons of the anterior horns at 12 h after SCI. Pretreatment with a JAK inhibitor, AG-490, suppressed phosphorylation of JAK1 and STAT3 at 12 h after SCI, reducing recovery of motor functions. These findings suggest that SCI at the acute stage produces IL-6 mainly in neurons of the injured spinal cord, which activates the JAK/STAT pathway, and that this pathway may be involved with neuronal response to SCI.

Animals↗
PubMed2006

Syndromic craniosynostosis with elbow joint contracture.

This paper reports a new type of syndromic craniosynostosis that was diagnosed by DNA analysis of the patient's fibroblast growth factor receptor (FGFR) genes. At birth, a male infant had ocular proptosis, a pseudotail, and obstructed respiration. He developed craniosynostosis, craniofacial dysmorphism, hydrocephalus, and bilateral contracture of his elbow joints. His treatment included fronto-orbital advancements and a ventriculoperitoneal shunt. Genetic analysis revealed that he was heterozygous for a missense mutation in exon 9 of the FGFR2 gene that resulted in an amino acid substitution of cysteine for serine at residue 351 (Ser351Cys). Seven cases with this mutation had previously been reported. All had severe craniosynostosis with midface hypoplasia, elbow joint contracture, developmental retardation, and early death.

Amino Acid Substitution↗
PubMed2006

[Glioma].

This chapter outlines the current clinical application of interferon for treatment of brain tumor, especially glioma. Since approved as a therapeutic drug for brain tumor originally produced in Japan, interferon-beta has been reported to be effective when it was used alone, in combination with chemo-radiotherapy (ACNU/MCNU as a nitrosourea derivative chemodrug, and radiation for 60 Gy totally). Recently, the regimen of combination with interferon-beta have been improved to obtain a higher efficacy rate. For example, as a fundamental study, temozolomide is an enthusiastic chemodrug to enhance the anti-tumor effect of interferon-beta when it is combined, pre-clinical and clinical trial will be scheduled. As for interferon-beta gene therapy by means of liposome as ad drug delivery system, already clinical trial has been performed and clinical safety and effectiveness have been proved, and it is expected that newly development in the field of gene therapy will be established and improvement of therapeutic results for malignant brain tumor will be achieved.

Antineoplastic Agents↗
PubMed2005

Susceptibility to exogenously added interferon-beta protein depends on intracellular interferon-beta mRNA level in human glioma cells.

Exogenously added human interferon-beta (HuIFN-beta) protein possesses a remarkable antiproliferative activity in human glioma and melanoma. Endogenous HuIFN-beta protein, which is produced by its gene transfer using cationic liposomes, has much more effective antiproliferative activity against these tumors, even in cells resistant to exogenously added HuIFN-beta protein. As the first step to elucidate the possible difference in antiproliferative mechanisms between exogenous and endogenous HuIFN-beta protein, we here investigated the relationship between the intracellular level of its mRNA and susceptibility to exogenously added HuIFN-beta protein. In this study, we used seven human glioma cell lines (SK-MG-1, SK-MG-4, SK-AO2, U87MG, U251SP, U251MG and T98) and one human melanoma cell line (MMAN). At first, we examined the relationship between spontaneous expression of HuIFN-beta mRNA and susceptibility to exogenously added HuIFN-beta protein (50 IU/ml) in human glioma cells and then confirmed a significant correlation between them. Next, we confirmed that administration of 0-100 IU/ml exogenously added HuIFN-beta protein upregulated the HuIFN-beta mRNA in a dose-dependent manner using the RT-PCR technique and that the HuIFN-beta mRNA was suppressed by siRNA for HuIFN-beta in SK-MG-1 and MMAN cells. Furthermore, we confirmed that the siRNA for HuIFN-beta significantly suppressed the antiproliferative effect of SK-MG-1 cells treated with 10-100 IU/ml HuIFN-beta protein and MMAN cells with 25 and 50 IU/ml HuIFN-beta protein. We found this phenomenon in another human glioma cell line, U87MG cells, as well. This finding would suggest that susceptibility to exogenously added HuIFN-beta protein is related to the amount of intracellular HuIFN-beta mRNA in human glioma and melanoma cells.

Cell Line, Tumor↗
PubMed2005

Brain metastases from apocrine carcinoma of the scalp: case report.

Apocrine carcinoma is an extremely rare malignant neoplasm that occurs most frequently in the axilla. Although it usually shows an indolent clinical course, it often metastasizes to regional lymph nodes and sometimes to lungs or bones. However, a literature search did not reveal any report describing the detailed clinical course of brain metastases from apocrine carcinoma. We report a case of a 54-year-old male who suffered from multiple brain metastases from apocrine carcinoma that had originated in the scalp 6 years before. The brain metastases appeared in spite of several regimens of chemotherapy for lung metastases for two years. The tumor in the right frontal lobe was successfully operated. However, the small tumor in the right occipital lobe was not cured by gamma knife surgery, and eventually required second operation. The operation had contributed to his neurologically independent life for about one year until he died for gradual progression of lung metastases. To our knowledge this is the first reported case of metastatic brain tumor from apocrine carcinoma.

Apocrine Glands↗
PubMed2005

IFN-beta down-regulates the expression of DNA repair gene MGMT and sensitizes resistant glioma cells to temozolomide.

Alkylating agents, such as temozolomide, are among the most effective cytotoxic agents used for malignant gliomas, but responses remain very poor. The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) plays an important role in cellular resistance to alkylating agents. IFN-beta can act as a drug sensitizer, enhancing toxicity against a variety of neoplasias, and is widely used in combination with other antitumor agents such as nitrosoureas. Here, we show that IFN-beta sensitizes glioma cells that harbor the unmethylated MGMT promoter and are resistant to temozolomide. By means of oligonucleotide microarray and RNA interference, we reveal that the sensitizing effect of IFN-beta was possibly due to attenuation of MGMT expression via induction of the protein p53. Our study suggests that clinical efficacy of temozolomide might be improved by combination with IFN-beta using appropriate doses and schedules of administration.

Antineoplastic Agents, Alkylating↗
PubMed2005

Intravitreal macrophage activation enables cat retinal ganglion cells to regenerate injured axons into the mature optic nerve.

In mature mammals, retinal ganglion cells (RGCs) are generally unable to regenerate injured axons into the optic nerve. Here, we report that an intravitreal injection of either of two macrophage activators, oxidized galectin-1 or zymosan, strongly enhanced the regeneration of transected RGC axons beyond an optic nerve crush site in adult cats. Using WGA-HRP as an anterograde tracer, we found that injection of either macrophage activator caused many axons to grow into the distal optic nerve when evaluated 14 days later, with the strongest effects seen after injecting 100 ng of galectin-1. Elongation continued for at least another 2 weeks. Control eyes injected with saline contained very few labeled axons extending across the crush site. Elevation of intracellular cAMP levels using forskolin also enhanced regeneration beyond the crush site to some extent, but this treatment did not augment the effect of galectin-1 any further. These results indicate that RGCs of adult cats are capable of reverting to an active growth state and at least partially overcoming an inhibitory CNS environment as a result of intravitreal macrophage activation.

Animals↗
PubMed2005

On the parity in helical twisting power of Ru(III) 1,3-diketonates of C2 symmetry in nematic liquid crystals.

It is demonstrated that the sign of helical twisting power (HTP) of an enantiomeric Ru(III) complex of type [Ru(acac)(2)L] can be switched by choosing L from either L(per) or L(para), which is elongated either perpendicular or parallel to the C(2) symmetry axis, and four states become available in combination with DeltaLambda-chirality of the metal center. Complexes 1-n, in which 4,4'-dialkoxylated dibenzoylmethanate ligands are used as L(per), and 2 having L(para) = 3-(4'-decyloxyphenyl)pentane-2,4-dionate ligand were prepared for this purpose. They were optically resolved into the enantiomers by means of a clay column chromatography, and their performance as chiral dopants was evaluated in nematic liquid crystals including a room-temperature system, N-methoxybenzylidene-4-n-butylaniline (MBBA), which allowed facile measurements of the helical pitch lengths and CD spectra in the induced chiral nematic states. The induced CD signals have provided a clear evidence for the helical inversion between the two structure types, 1 and 2, of the same chirality. The twisting power of these six-coordinate metal complexes and their structure versus twist sense correlations are interpreted by the shape model. Intrinsically high HTP of Delta-[Ru(acac)(2)L(per)] has also allowed for observation of the pitch band due to the selective reflection in the visible wavelength range at the doping level of 2 mol % in MBBA.

Journal Article↗
PubMed2005

Irinotecan therapy in a 12-year-old girl with recurrent brain stem glioma and without functional polymorphisms in UGT1A1 activity: case report.

A 10-year-old girl was diagnosed with astrocytoma grade 2. Immuno-chemo-radiotherapy (interferon, ranimustine, and radiation), second-line chemotherapy (carboplatin and etoposide, 7 cycles) and third-line chemotherapy (ifosfamide, carboplatin, and etoposide) was given to treat progressive disease. Finally, irinotecan therapy was initiated and led to dramatic clinical improvement. Irinotecan is metabolized by carboxylesterase to form an active SN-38, which is further conjugated and detoxified by UDP-glucuronosyltransferase (UGT) to yield its beta-glucuronide. The polymorphic UGT isoenzyme, UGT1A1 has genetic variants which decrease in SN-38 glucuronidating capacity and could help predict irinotecan-associated toxicity. The patient suffered excessive toxicity with low-dose irinotecan although no functional polymorphism in UGT1A1 was identified. We suggest that irinotecan offers an effective treatment option for children with recurrent brain stem glioma and other genetic variants except UGT1A1 may be a risk factor for irinotecan-induced toxicity.

Antineoplastic Agents, Phytogenic↗