Biomedical subjects

K Kajiwara

Publications and source records attributed to K Kajiwara.

At least 19 recordsLinked to original sources

PubMed2006

Designing novel pH-sensitive non-phospholipid vesicle: characterization and cell interaction.

In this work, we report the preparation, the characterization and interaction with cells of novel pH-sensitive non-phospholipid vesicle formulations, from a non-ionic surfactant mixed with cholesterol (CHOL) and his derivative cholesteryl hemisuccinate (CHEMS), as pH-sensitive molecule. This molecule, can destabilize the vesicle lipid bilayer when exposed to an acidic environment, with a subsequent release of vesicular content, enhancing the cytoplasmatic delivery of drugs to target cells. Vesicles were characterized by static and dynamic light scattering, in order to evaluate their dimensions, bilayer thickness and vesicle stability. Membrane permeability changes were determined by the release of entrapped hydroxypyrene-1,3,6-trisulfonic acid (HPTS). Also diphenylhesatriene (DPH) fluorescence anisotropy and zeta potential measurements were used to evidence the pH sensitivity. Furthermore vesicles were characterized by means of electronic microscopy after freeze-fracture. The interaction of non-lipid vesicles containing different fluorescent dyes with Raw 264.7, mouse monocite macrophage, were analyzed by flow cytometric analysis. The obtained results indicate that the pH-sensitive vesicular structures show good plasma stability and relevant pH-sensitivity. Moreover this formulation was able to interact with target membranes (i.e. plasma or endosomal membrane) and to release the encapsulated material into the cytoplasm.

Animals↗

PubMed2006

CyberKnife stereotactic radiotherapy for patients with malignant glioma.

OBJECTIVE: The CyberKnife is a new frameless image-guided radiosurgical modality. The authors report on their experience using the CyberKnife in 25 patients with malignant gliomas. METHODS: Twenty-five patients with histologically proven malignant gliomas (18 glioblastoma: GB, 7 anaplastic astrocytoma: AA) were treated with the CyberKnife at Konan St. Hill Hospital between June 1998 and November 2002. CyberKnife therapy was performed on 44 lesions (31 GB lesions, 13 AA lesions) in the 25 patients. The median target volume was 19.1 mL (range: 0.3 - 90.2). The median prescribed dose was 20.3 Gy (range: 13.9 - 26.4). Patient-, tumor-, and treatment-related variables were analyzed by univariate analysis, and survival curves were generated by the Kaplan-Meier product limit. RESULTS: In the 18 GB patients, the median survival after diagnosis was 20.7 months (82.6 weeks) with a mean follow-up of 85.7 weeks. Of the 7 AA patients, 6 were alive at the time of analysis with follow-up periods ranging from 11.4 to 52.8 months. Patients younger than 70 years had a median survival after diagnosis of 37.1 months, compared to 12.4 months for older patients (p = 0.003). Similarly, patients with well-controlled lesions had a median survival after diagnosis of 39.8 months compared to 16.0 months for those with uncontrolled lesions (p = 0.031). Late delayed radiation necrosis was seen in 1 GB patient. No other patient suffered acute or delayed neurological morbidity after CyberKnife therapy. CONCLUSION: This is the first report of CyberKnife stereotactic radiotherapy applied to the treatment of malignant gliomas. The frameless and painless CyberKnife stereotactic radiotherapy has the potential to be as useful for treatment of malignant glioma as other radiosurgical modalities.

Adult↗

PubMed2006

The role of cyberknife radiosurgery/radiotherapy for brain metastases of multiple or large-size tumors.

OBJECTIVE: Focused, highly targeted radiosurgery and fractionated radiotherapy using the Cyberknife are useful treatments for multiple or large metastases. Here we present our results of Cyberknife radiosurgery for 71 patients with 148 metastatic brain lesions. METHODS: There were 32 women and 39 men with a median age of 63 (range: 30-88) years. Radiographic follow-up was available for 60 patients with 104 lesions. The mean and median initial volumes of the tumor per lesion were 6.6 and 2.9 cm(3) (range: 0.1-53.2 cm(3)), respectively, at the time of the initial Cyberknife treatment. Forty patients (56%) had a single lesion, and 31 (44%) had multiple lesions (range: 2-7) at initial treatment. The number of fractions ranged from 1 to 3, and forty (27%) of 148 lesions were treated by a fractionated course of Cyberknife therapy. The mean marginal dose was 20.2 Gy (range 7.8-30.1 Gy, median: 20.7 Gy). RESULTS: At 44 weeks of median follow-up, there were no permanent symptoms resulting from radiation necrosis. Overall 6-month and 1-year survival rates were 74% and 47%, respectively, and the median survival time was 56 weeks. The Karnofsky performance score and extracranial metastasis were significant prognostic factors at 6 months and 1 year, respectively, in both univariate and multivariate analyses. Age or multiple metastases did not influence prognosis at 6 months and 1 year. Local control was achieved in 83% (86 lesions). After additional radiosurgical or surgical salvage, no patient died as a result of intracranial disease. Twenty-five patients developed 92 new metastases (range 1-13) outside of the treated lesions with 22.4 weeks of median follow-up. Among them, 21 patients (84 lesions) were treated by salvage Cyberknife. CONCLUSION: Despite the inclusion of an unfavorable group of patients with large tumors, our results for survival and tumor control rates are comparable to those of published series. The Cyberknife provides the advantage of allowing for fractionated treatment to multiple or large-size tumors.

Adult↗

PubMed2005

Image-guided stereotactic radiosurgery with the CyberKnife for pituitary adenomas.

This study demonstrates the clinical usefulness of image-guided fractionated stereotactic radiosurgery with the CyberKnife system. Twenty-one patients with pituitary adenomas received image-guided stereotactic radiosurgery with the CyberKnife, and were followed up for more than 18 months. The patients consisted of 14 with non-functioning adenomas, 3 with prolactinomas, 2 with acromegaly, and 2 with ACTH-producing tumors. In 20 cases, fractionated radiosurgery was performed. The change in the tumor volume, visual acuity, hormonal function, and complications by this therapy were analyzed in each case. The volume of the tumors ranged from 0.2 cm (3) to 34.9 cm (3) (mean +/- SD: 11.3 +/- 9.2 cm (3)). The mean volumes of the non-functioning and functioning adenomas were 13.3 cm (3) and 7.5 cm (3), respectively. The marginal irradiation dose ranged from 6.4 Gy to 27.7 Gy (mean: non-functioning adenomas 12.6 Gy, functioning adenomas 17.5 Gy), as a dose of a single fraction. The follow-up periods ranged from 18 months to 59 months (mean +/- SD: 35.3 +/- 10.7 months). The tumor control rate was 95.2 %. In 1 case, visual acuity worsened due to cystic enlargement of the tumor. Hormonal function improved in all of the 7 functioning adenomas. The hormone level normalized in 1 prolactinoma, and decreased to less than normal in 1 ACTH-producing adenoma. In 2 cases, hypopituitarism occurred after the therapy. Image-guided stereotactic radiosurgery with the CyberKnife is effective and safe against relatively large pituitary adenomas. Careful long-term follow-up of the patients is necessary because of delayed cystic enlargement of the tumor in rare cases.

Adenoma↗

PubMed2004

CyberKnife radiosurgery for vestibular schwannoma.

OBJECTIVE: The CyberKnife is newly developed equipment for radiosurgery and fractionated radiosurgery. The authors report on their experience using the CyberKnife in 38 patients with vestibular schwannoma who were treated between 1998 to 2002. METHODS: During this period, 38 patients with vestibular schwannoma were treated using CyberKnife fractionated radiosurgery. Before undergoing fractionated radiosurgery, 14 patients had Gardner Robertson classes I or II hearing (the serviceable hearing group), and 24 patients had classes III to V hearing (the non-serviceable hearing group). The treatment volumes of these two groups were 0.5 to 24.0 cm (3) (mean 4.7 cm (3)), and 0.5 to 41.6 cm (3) (mean 8.2 cm (3)). Target irradiation was administered in 1 - 3 fractions (mean 2.5 fractions). The total marginal radiation doses were 15.0 to 20.5 Gy (mean 17.0 Gy), and 11.9 to 20.1 Gy (mean 16.9 Gy), respectively. RESULTS: After a mean follow-up period of 31.9 months (range 12 to 59 months, median 27 months), 94 % of the tumors were controlled. Only one patient in the group with non-serviceable hearing underwent additional surgical resection for a presumed increase in tumor size. The hearing preservation rate was 93 %. Facial weakness did not develop in any of the patients in the serviceable hearing group. New trigeminal symptoms did not develop in any patients in either group. CONCLUSION: Although a longer and more extensive follow-up is needed, CyberKnife fractionated radiosurgery is considered to be safe and effective, even in patients with large tumors.

Adolescent↗

PubMed2003

Identification of dislocations in large tetragonal hen egg-white lysozyme crystals by synchrotron white-beam topography.

Large tetragonal hen egg-white (HEW) lysozyme crystals have been grown by a salt concentration-gradient method. The grown crystals, of thicknesses greater than 1.5 mm, were observed by means of X-ray topography using white-beam synchrotron radiation. Line contrasts clearly appeared on the Laue topographs. Extinction of the line images was observed in specific reflections. These results mean that the observed lines correspond to dislocation images. From the extinction criterion it is shown that the predominant dislocations are of screw character with <110> Burgers vectors. In addition, dislocation loops with [001] Burgers vectors have been found in a tetragonal HEW lysozyme crystal including some cracks. These results are discussed in the light of dislocation elastic energy and slip systems in the crystals.

Animals↗

PubMed2003

Image-guided transsphenoidal surgery for pituitary lesions using Mehrkoordinaten Manipulator (MKM) navigation system.

Twenty-five patients with pituitary lesions were operated on by image-guided transsphenoidal surgery (TSS) using the Mehrkoordinaten Manipulator (MKM) navigation system. The cases included 21 cases of pituitary adenomas, 2 cases of craniopharyngioma and 2 cases of Rathke's cleft cyst. All operations were performed through the sublabial approach under an operative microscope. In some cases, an endoscope was used for the observation of the residual tumor and surrounding structures. The tumors and surrounding important structures such as the internal carotid arteries, the basilar artery, and the optic nerves were precisely localized, and mechanical error was less than 2 mm in almost all cases. In 3 early cases of pituitary adenoma, the patient's head was moved slightly during the insertion of the nasal speculum; in these cases, the resulting error was more than 2 mm. In evaluating the procedures, we determined that the most useful benefit of the MKM system compared with other systems is that the navigation information is not only displayed on the monitor, but also presented in the operative field under the microscope. Therefore, the surgeon can obtain the navigation information without removing his eyes from the operative field under the microscope. The most important drawback to the system is its bulky size.

Adenoma↗

PubMed2002

Synchrotron-radiation X-ray topography of surface strain in large-diameter silicon wafers.

Using a 300 mm-wide monochromatic X-ray beam obtained at beamline BL20B2 of SPring-8, the difference in surface-strain distribution caused by various steps of silicon-wafer manufacturing, i.e. slicing, lapping, etching, grinding and polishing, was studied. The asymmetric 511 reflection of 21.45 keV X-rays, incident at a glancing angle of 0.26 degrees, was used to obtain topographs over the whole surface of a 200 mm-diameter (100) CZ silicon wafer. Differences in crystallinity and in warp between the surfaces at different steps of the manufacturing process (firstly after the lapping following the slicing, and then after successive etching, grinding and polishing) were clearly observed. The former gave a topographic image over the whole area with a one-shot exposure because of their wide rocking curves (50-70 arcsec FWHM), which indicate poor crystallinity. The latter, on the other hand, showed sharper curves (4-5 arcsec FWHM), which indicate good crystallinity in local areas, and the existence of warp, and therefore required step scanning of omega-rotation to cover the whole surface in topography measurements. The effect of each step in the process is also discussed.

Journal Article↗

PubMed2001

Prolonged survival of xenograft fetal cardiomyocytes by adenovirus-mediated CTLA4-Ig expression.

BACKGROUND: Experimental allografting of fetal cardiomyocytes has been performed successfully. In this study, we attempted to transplant rat fetal cardiomyocytes into the hearts of mice by blocking the CD28/B7 costimulatory pathway via CTLA4-Ig gene transfer. METHODS: Fetal cardiomyocytes derived from Dark Agouti rat were infected with CTLA4-Ig-expressing adenovirus vectors (AdCTLA) and injected directly into the normal myocardium of C3H/He mice (n=15). For control, cells infected with beta-Gal-expressing adenovirus vector (AdRL) and cells without infection were injected into additional mice (n=30). Mice were killed at 2 (n=5), 4 (n=5), and 8 (n=5) weeks after xenotransplantation. Transplanted fetal cardiomyocytes were examined for survival by immunostaining with anti-rat atrial natriuretic peptide and anti-CTLA4-Ig antibodies. RESULTS: Fetal cardiomyocytes were successfully infected by AdCTLA and AdRL. The cardiomyocytes infected with AdCTLA expressed CTLA4-Ig and survived to 8 weeks after xenotransplantation in all of these mice. However, cardiomyocytes infected with AdRL and noninfected cells were not detected even 2 weeks after xenotransplantation. CONCLUSION: Survival of xenografted fetal cardiomyocytes is prolonged by adenovirus-mediated CTLA4-Ig expression.

Abatacept↗

PubMed2001

PKCdelta and zeta mediate IL-4/IL-13-induced germline epsilon transcription in human B cells: a putative regulation via PU.1 phosphorylation.

We have investigated the role of PKC isozymes in the function of IL-4 and IL-13 in human B cells. In a Burkitt's B lymphoma cell line, DND39, IL-4 induced the translocation of PKCdelta and zeta from the cytosol to the membrane fraction. The activation of germline epsilon promoter by IL-4 was abrogated not only by the expression of dominant negative mutants of PKCdelta and zeta but also by isozyme-selective PKC inhibitors, rottlerin and PKCzeta pseudosubstrate peptide. These inhibitors also suppressed IL-4/IL-13-induced germline epsilon transcription in the IL-13Ralpha1-transfected DND39 cells as well as in normal human B cells, but had no influence on the induction of CD23b in the latter cells. As a downstream event of PKC, we found threonine phosphorylation of PU.1 in IL-4-stimulated DND39 cells. This phosphorylation was suppressed by the PKC inhibitors, although STAT6 activation was unaffected. These results suggest that, in human B cells, IL-4/IL-13 utilize PKCdelta and zeta for the STAT6-independent signaling pathway and thereby modulate the transcriptional activity of PU.1.

B-Lymphocytes↗

PubMed2001

Low-degree oxidized scleroglucan and its hydrogel.

A controlled oxidation of scleroglucan was performed with sodium periodate to prepare aldehyde derivatives (scleraldehyde) with a low degree of oxidation (10 and 20%), which were utilized for crosslinking reactions with hexamethylenediamine. The structural characterization of scleraldehydes and their corresponding hydrogels was attempted by small-angle X-ray scattering (SAXS). While scleraldehyde with a higher degree of oxidation (> or = 50%), according to an earlier research, was found to disentangle into single chains as the degree of oxidation increases; scleroglucan bearing a low percentage of aldehydic groups (up to 20%) retains mainly the conformation of the natural polysaccharide, thus the system can be represented as composed of triple helices with only minor disentanglements at the sites where the aldehyde groups are present. The hydrogel prepared from scleraldehyde with a low degree of oxidation is brittle and fragmented, in contrast to the elastic/homogeneous hydrogel earlier prepared from scleraldehyde with a high degree of oxidation. The hydrogel from scleraldehyde with a low degree of oxidation was found to possess a network structure that consisted mostly of the triple helices crosslinked in specific points where the triple helices are disentangled into single chains because of the presence of the aldehyde groups.

Aldehydes↗

PubMed2001

Increase of ceramides and its inhibition by catalase during chemically induced apoptosis of HL-60 cells determined by electrospray ionization tandem mass spectrometry.

A change in all ceramide species during chemically induced apoptosis of HL-60 cells was determined using electrospray tandem mass spectrometry. Ceramides of C16:0, C24:1 and C26:1 increased significantly 4 h after the addition of actinomycin D, when the activation of caspase-3 was maximal. Addition of catalase, which inhibited apoptosis, the activation of caspase-3-like protease, and the release of cytochrome c from mitochondria to cytosol caused by actinomycin D or daunorubicin, significantly inhibited the increase of these ceramides at all time points. Ceramides of C16:0, C24:1, C18:0, C22:1 and C26:1 increased significantly 4 h after the addition of daunorubicin to HL-60 cells. Catalase also significantly inhibited the increase of these ceramides induced by daunorubicin. Based on time courses of events and inhibition studies, it is concluded that the increase of ceramides is downstream from both generation of hydrogen peroxide and cytochrome c release from mitochondria and takes place almost simultaneously with the activation of caspase-3.

Apoptosis↗

PubMed2001

Co-administration of adenovirus vector expressing CTLA4-Ig prolongs transgene expression in the brain of mice sensitized with adenovirus.

The duration of transgene expression in the brain is known to be shortened by previous sensitization to adenovirus. In order to prolong transgene expression, adenovirus vectors expressing CTLA4-Ig (AdCTLA), which blocks the B7-CD28 co-stimulatory signals required for T-cell activation, were used. Local administration of AdCTLA into the brain suppressed both the cellular and humoral immune responses to adenovirus vectors, and prolonged the duration of transgene expression. AdCTLA may be an effective tool for repeated gene transfer.

Abatacept↗

PubMed2001

Hydrogen peroxide and hydroxyl radical involvement in the activation of caspase-3 in chemically induced apoptosis of HL-60 cells.

Apoptosis of HL-60 cells induced by actinomycin D, H7, or daunorubicin was shown to involve the activation of caspase-3-like protease, 2 h after the addition of these drugs, based on microassay of enzyme activity by high-performance liquid chromatography. Catalase and a spin trap, N-t-butyl-alpha-phenylnitrone, which effectively inhibited the apoptosis induced by these drugs, also inhibited the activation of caspase-3-like protease. These results suggest that hydrogen peroxide and the hydroxyl radical are common mediators of caspase-3 activation caused by these chemicals, with apparently different functional mechanisms. Based on mitochondrial activity determined by oxygen consumption, complexes I, II, and IV were inhibited by actinomycin D. H7 inhibited complexes I and IV, 1 and 1.5 h respectively, after the addition of the drug to HL-60 cells. Daunorubicin inhibited complex IV, 1.5 h after the addition of the drug to HL-60 cells. Inhibition of complex IV by actinomycin D, H7, and daunorubicin were almost fully restored by the addition of cytochrome c. The release to the cytosol of cytochrome c by these drugs was also demonstrated by Western blot analysis. Addition of catalase inhibited the depression of complex IV activity induced by actinomycin D and H7. These observations indicate a direct relationship between hydrogen peroxide and the release of cytochrome c during apoptosis caused by actinomycin D, H7, and daunorubicin.

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

PubMed2001

Sez4 gene encoding an elongation subunit of DNA polymerase zeta is required for normal embryogenesis.

BACKGROUND: Sez4 identified as a seizure-activated gene shows a similarity to the yeast REV3 that encodes a catalytic subunit of the nonessential DNA polymerase zeta which is involved in error-prone translesion synthesis. Although yeast REV3 homologues in mouse and human have recently been identified and characterized, their precise roles remain elusive. RESULTS: Here we investigated the role of mouse pol zeta by targeted inactivation of the Sez4 gene. The homozygous Sez4 mutants died around embryonic day (E) 10.5. This lethal effect was the result of developmental defects and apoptotic cell death within the embryo proper at the gastrulation stage, and it was partially rescued at E12.5 by the expression of a Sez4-transgene. In wild-type embryos, Sez4 transcripts were up-regulated within the embryo proper from E7.5, correlating well with the lethal stage of Sez4-inactivation. CONCLUSION: Our findings indicate that Sez4 is essential for epiblast lineage-specific development and suggests a requirement of mammalian DNA polymerase zeta in the survival of certain subcellular populations which are indispensable to normal embryogenesis.

Animals↗

PubMed2001

Stimulation of catecholamine synthesis in cultured bovine adrenal medullary cells by leptin.

Recently, we characterized leptin receptors in bovine adrenal medullary cells (Yanagihara et al. 2000). Here we report the stimulatory effect of leptin on catecholamine synthesis in the cells. Incubating cells with leptin (10 nM) for 20 min increased the synthesis of 14C-catecholamines from [14C]tyrosine, but not from L-3,4-dihydroxyphenyl [3-14C]alanine. The stimulation of catecholamine synthesis in the cells by leptin was associated with the phosphorylation and activation of tyrosine hydroxylase, the rate-limiting enzyme of catecholamine biosynthesis. The incubation of cells with leptin resulted in a rapid activation of the mitogen-activated protein kinases (MAPKs). An inhibitor of MAPK kinase, U0126, nullified the stimulatory effect of leptin on the synthesis of 14C-catecholamines. Leptin potentiated the stimulatory effect of acetylcholine on 14C-catecholamine synthesis, whereas leptin failed to enhance the phosphorylation and activation of tyrosine hydroxylase induced by acetylcholine. These findings suggest that leptin stimulates catecholamine synthesis via the activation of tyrosine hydroxylase by two different mechanisms, i.e., one is dependent on tyrosine hydroxylase phosphorylation mediated through the MAPK pathway and the second is independent of enzyme phosphorylation.

Acetylcholine↗

PubMed2001

Detection of craniospinal dissemination of intracranial germ cell tumours based on serum and cerebrospinal fluid levels of tumour markers.

Nineteen intracranial germ cell tumours treated during the past 11 years were evaluated retrospectively. The tumours were classified into three groups according to the level of alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) in serum and cerebrospinal fluid, and the optimal treatment for each group was determined. Group A consisted of patients with normal titres of AFP and HCG, group B of patients with relatively high titres (< 10 times normal), and group C comprised patients with higher titres ( 10 times normal levels). In group A, an appropriate field and dose of irradiation was necessary to prevent craniospinal dissemination. In group B, none of four patients who underwent total or subtotal resection of the tumour had craniospinal disseminatio n or tumour recurrence, whereas dissemination occurred in four further patients, including two who had received radiochemotherapy only, and two who had undergone partial resection of the tumour. While patients in group C had dissemination at the time of initial diagnosis, most patients in group B developed dissemination more than 10 months after initial treatment, suggesting that the type of treatment received as first line therapy is important in patients in this group. The prognosis of patients in group C, however, was unaffected by the priority given to either surgery, radiation or chemotherapy as first line treatment. Craniospinal dissemination can be prevented in patients with germ cell tumours who have a relative increase in levels of AFP and HCG by aggressive removal of the tumours as first line therapy, regardless of the type of adjuvant therapy given.

Adolescent↗

PubMed2001

The error-prone DNA polymerase zeta catalytic subunit (Rev3) gene is ubiquitously expressed in normal and malignant human tissues.

Mutagenesis induced by UV light and chemical agents in yeast is largely dependent on the function of Rev3, the catalytic subunit of DNA polymerase zeta that carries out translesion DNA synthesis. Human and mouse homologues of the yeast Rev3 gene have recently been identified, and inhibition of Rev3 expression in cultured human fibroblasts by Rev3 anti-sense was shown to reduce UV-induced mutagenesis, indicating that Rev3 also plays a crucial role in mutagenesis in mammalian cells. A common variant transcript with an insertion of 128-bp between nucleotides +139 and +140 is found in both human and mouse Rev3 cDNAs, but its biological significance has not been defined. We show here that the insertion variant is not translatable either under in vitro or in vivo conditions. We also found that the translational efficiency of Rev3 gene is enhanced by the 5' untranslated region that contains a putative stem-loop structure postulated to inhibit the translation. Since the human Rev3 gene is localized to chromosome 6q21, a region previously shown to contain genes involved in tumor suppression and cellular senescence, we examined its expression in various normal and malignant tissues. Rev3 and its insertion variant transcripts were ubiquitously detected in all 27 normal human tissues studied, with an additional variant species found in tissues with relatively high levels of Rev3 expression. Levels of Rev3 transcripts were similar in lung, gastric, colon and renal tumors compared to normal tissue counterparts. The data indicate that Rev3 expression is ubiquitous and is not dysregulated in malignancies.

5' Untranslated Regions↗