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Biomedical subjects

Hideo Nakamura

Publications and source records attributed to Hideo Nakamura.

At least 19 recordsLinked to original sources
PubMed2006

Design, synthesis, and evaluation of novel kazusamycin A derivatives as potent antitumor agents.

Novel kazusamycin A derivatives were designed in the viewpoint of decrease of reactivity at the alpha,beta-unsaturated delta-lactone moiety against Michael-type addition. Although 25-30 steps were required for the synthesis of each compound, their syntheses were achieved. Cytotoxicity against HPAC cell line was evaluated, and two of them exhibited comparable potency to kazusamycin A. Hepatic toxicity of these designed compounds was much lower than that of kazusamycin A.

Antineoplastic Agents↗
PubMed2006

In vitro stimulation of CD8 and CD4 T cells by dendritic cells loaded with a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein: Identification of a new HLA-DR15-binding CD4 T-cell epitope.

PURPOSE: NY-ESO-1 belongs to a class of cancer/testis antigens and has been shown to be immunogenic in cancer patients. We synthesized a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein (CHP/ESO) and investigated the in vitro stimulation of CD8 and CD4 T cells from peripheral blood mononuclear cells in healthy donors with autologous CHP/ESO-loaded dendritic cells as antigen-presenting cells. EXPERIMENTAL DESIGN: In vitro stimulation of CD8 or CD4 T cells was determined by IFNgamma ELISPOT assays against autologous EBV-B cells infected with vaccinia/NY-ESO-1 recombinant virus or wild-type vaccinia virus as targets and by ELISA measuring secreted IFNgamma. RESULTS: NY-ESO-1-specific CD8 and CD4 T cells were induced. In a donor expressing HLA-A2, CD8 T cells stimulated with CHP/ESO-loaded dendritic cells recognized naturally processed NY-ESO-1(157-165), an HLA-A2-binding CD8 T cell epitope. NY-ESO-1 CD4 T cells were Th1-type. We identified a new HLA-DR15-binding CD4 T cell epitope, NY-ESO-1(37-50). CONCLUSIONS: These findings indicate that CHP/ESO is a promising polyvalent cancer vaccine targeting NY-ESO-1.

Amino Acid Sequence↗
PubMed2006

ESR detection of wheat flour before and after irradiation.

We revealed free radicals in wheat flour before and after gamma-ray irradiation and their thermal behavior during heat-treatment using electron spin resonance (ESR) spectroscopy. The ESR spectrum of wheat flour before irradiation consists of a sextet centered at g = 2.0 and a singlet signal at the same g-value position. The first one is attributable to a signal with hyperfine (hf) interactions of Mn2+ ion (hf constant: 7.4 mT). The second is originated from carbon-centered radical. Upon gamma-ray irradiation, however, a new signal with two triplet lines at the low and high field ends was detected in wheat flour on top of the Mn2+ sextet lines. We analyzed the triplet ESR lines as powder spectra (rhombic g-tensor symmetry) with nitrogen (14N) hyperfine interactions. This indicates that a new organic radical was induced in the conjugated protein portion of wheat flour by the gamma-ray irradiation. Intensity of the organic free radical at g = 2.0 detected in irradiated wheat flour increased monotonically by the thermal treatment. The analysis of the time-dependent evolution and decay process based on the theory of transient phenomena as well as the nonlinear least-squares numerical method provided a unique time constant for the radical evolution and decay in wheat flour during the heat-treatment.

Dose-Response Relationship, Radiation↗
PubMed2006

An ESR protocol based on relaxation phenomena of irradiated Japanese pepper.

We found various free radicals in a commercially available pepper in Japan before and after irradiation using electron spin resonance (ESR) spectroscopy. The typical ESR spectrum of the pepper consists of a sextet centered at g = 2.0, a singlet at the same g-value and a singlet at g = 4.0. Upon gamma ray irradiation, a new pair of signals appeared in the pepper. The progressive saturation behavior (PSB) at various microwave power levels indicated quite different relaxation behaviors of those radicals. Namely, the peak intensity of the organic free radical component decreases in a monotonic fashion, whereas the Mn2+ and Fe3+ ESR signals substantially keep constant. This reflects the evidence of three independent radicals in the pepper before irradiation. The PSB of the pair peaks as induced by irradiation possessed quite different PSB from that of the free radical located at g = 2.0. We proposed a new protocol for the ESR detection of irradiated foods by the PSB method at different microwave power levels. This would call for a major modification of the CEN protocol in European Union.

Dose-Response Relationship, Radiation↗
PubMed2006

An electron spin resonance study of gamma-ray irradiated ginseng.

Using electron spin resonance (ESR) spectroscopy, we revealed the presence of four radical species in gamma-ray irradiated ginseng (Agaliaceae). Before irradiation, the representative ESR spectrum of ginseng is composed of a sextet centered at g = 2.0, a sharp singlet at the same g-value, and a singlet at about g = 4.0. The first one is attributable to a hyperfine (hf) signal of Mn2+ ion (hf constant: 7.4 mT). The second one is due to an organic free radical. The third one is originated from Fe3+. Upon gamma-ray irradiation, a new ESR (the fourth) signal was detectable in the vicinity of g = 2.0 region. The progressive saturation behaviors of the ESR signals at various microwave power levels were indicative of different relaxation time for those radicals. The anisotropic ESR spectra were detected by the angular rotation of the sample tube. This is due to the existence of anisotropic microcrystalline in the ginseng powder sample.

Dose-Response Relationship, Radiation↗
PubMed2006

A long-term ventricular drainage for patients with germ cell tumors or medulloblastoma.

BACKGROUND: Hydrocephalus associated with intracranial germ cell tumors or disseminated medulloblastoma has been treated with ventriculoperitoneal shunt. However, this procedure has a potential risk of intraperitoneal metastasis of these brain tumors. To prevent this potential risk and to minimize the risk of infection, we developed a percutaneous long-tunneled ventricular drainage (PLTVD). To confirm the effectiveness, we retrospectively analyzed the results of this procedure. METHODS: From 1979 to 2003, we have treated 96 patients with germ cell tumors and medulloblastoma in our hospital. Of 96 patients, 59 (germ cell tumor, 31; medulloblastoma, 28) had hydrocephalus and 13 needed long-term cerebrospinal fluid drainage to manage the obstructive hydrocephalus due to persistent tumor or communicating hydrocephalus due to dissemination. We performed PLTVD for these cases using a flow-controlled shunt device and percutaneous long-tunneled shunt tube (peritoneal catheter) exiting at the upper abdomen and connecting to a closed drainage system. The occurrence of extraneural metastasis and the incidence of infection were evaluated. RESULTS: The average duration of drainage was 74 days (range, 34-115 days). All 13 cases received full-dose chemotherapy and radiotherapy without infectious complications or extraneural metastasis. CONCLUSIONS: Percutaneous long-tunneled ventricular drainage was an effective method to manage long-lasting obstructive or communicating hydrocephalus with germ cell tumors and medulloblastoma.

Adolescent↗
PubMed2006

Rising incidence of primary central nervous system lymphoma in Kumamoto, Japan.

BACKGROUND: Primary central nervous system lymphoma is an extranodal form of non-Hodgkin lymphoma arising in the craniospinal axis. The incidence of PCNSL is reportedly on the increase in some parts of the world in the last 2 decades. METHODS: We surveyed 4007 patients diagnosed with PIT between 1989 and 2004, with histologic diagnosis being obtained in 70% of the patients. Of these, the PCNSL cases were reviewed. RESULTS: Of 4007, 136 (3.4%) carried a diagnosis of PCNSL. At 0.41 per 100,000 per year, the age-adjusted incidence rate for that period was higher than that for the period from 1989 to 1998 (0.29 per 100,000 per year). Moreover, the number of patients with PCNSL doubled from 45 (1989-1996) to 91 (1997-2004). CONCLUSIONS: Our findings point to an increase in the incidence of PCNSL among immunocompetent individuals in Kumamoto Prefecture.

Age Distribution↗
PubMed2006

Recurrent intracranial germinoma outside the initial radiation field: a single-institution study.

Between 1975 and 2005, we treated 52 newly diagnosed germinoma patients. Until 1991, patients with pure germinomas or germinomas with syncytiotrophoblastic giant cells (STGCs) received whole-brain radiotherapy only. Of the 52 patients, 30 were treated with a reduced radiation volume and combined chemotherapy; seven of these received local irradiation with 24 Gy, two received whole-brain (30 Gy) plus local irradiation (20 Gy), 16 received extended local irradiation delivered to the whole ventricles (30 Gy) plus local (20 Gy) irradiation, and five received extended local irradiation (24 Gy). Of the 30 patients treated with a reduced radiation volume and combined chemotherapy, four experienced tumor recurrence; three patients had been treated with 24 Gy of local radiotherapy and one had received extended local (30 Gy) plus local (20 Gy) irradiation in addition to chemotherapy. In these patients, the delivered radiotherapy was inadequate and the origin of the recurrent tumors was outside the radiation field. None of the patients who had received at least 24 Gy of whole ventricle radiotherapy combined with chemotherapy experienced tumor recurrence. In combination with chemotherapy, the delivery of irradiation covering the ventricles effectively reduced the incidence of tumor recurrence in patients with germinomas or germinomas with STGCs.

Adolescent↗
PubMed2006

[Efficacy and safety of monotherapy with temozolomide in patients with anaplastic astrocytoma at first relapse--a phase II clinical study].

The efficacy and safety of temozolomide were evaluated in 32 patients with anaplastic astrocytoma at first relapse. Temozolomide was administered orally once daily for the first five days of a 28-day cycle, at a dose of 150 or 200 mg/m(2)/day. The response rate determined by independent central review of MRI was 34% (95% confidence interval: 18.6%-53.2%), with 3 complete response and 8 partial response. The rate of "no change or better" was 91% (95% confidence interval: 75.0%-98.0%). Progression-free survival (PFS) at 6 months was 40.6%, and the median PFS was 4.1 months. The incidence of constipation (50%) and nausea (25%) was high,but these events were all mild or moderate in severity except in one subject with constipation,and could be managed with standard laxatives and antiemetics. The main laboratory test abnormalities (total incidence and incidence of grade 3/4 change) were lymphocytopenia (50%, 25%), neutropenia (47%, 6%), leukopenia (38%, 3%), thrombocytopenia (31%, 9%), and increased GPT (25%, 3%). Temozolomide was shown to have good efficacy and tolerability in patients with anaplastic astrocytoma at first relapse.

Adult↗
PubMed2005

Conformational change in full-length mouse prion: a site-directed spin-labeling study.

The structure of the mouse prion (moPrP) was studied using site-directed spin-labeling electron spin resonance (SDSL-ESR). Since a previous NMR study by Hornemanna et al., [Hornemanna, Korthb, Oeschb, Rieka, Widera, Wüthricha, Glockshubera, Recombinant full-length murine prion protein, mPrP (23-231): purification and spectroscopic characterization, FEBS Lett. 413 (1997) 277-281] has indicated that N96, D143, and T189 in moPrP are localized in a Cu(2+) binding region, Helix1 and Helix2, respectively, three recombinant moPrP mutations (N96C, D143C, and T189C) were expressed in an Escherichia coli system, and then refolded by dialysis under low pH and purified by reverse-phase HPLC. By using the preparation, we succeeded in preserving a target cystein residue without alteration of the alpha-helix structure of moPrP and were able to apply SDSL-ESR with a methane thiosulfonate spin label to the full-length prion protein. The rotational correlation times (tau) of 1.1, 3.3, and 4.8ns were evaluated from the X-band ESR spectra at pH 7.4 and 20 degrees C for N96R1, D143R1, and T189R1, respectively. tau reflects the fact that the Cu(2+) binding region is more flexible than Helix1 or Helix2. ESR spectra recorded at various temperatures revealed two phases together with a transition point at around 20 degrees C in D143R1 and T189R1, but not in N96R1. With the variation of pH from 4.0 to 7.8, ESR spectra of T189R1 at 20 degrees C showed a gradual increase of tau from 2.9 to 4.8ns. On the other hand, the pH-dependent conformational changes in N96R1 and D143R1 were negligible. These results indicated that T189 located in Helix2 possessed a structure sensitive to physiological pH changes; simultaneously, N96 in the Cu(2+) binding region and D143 in Helix1 were conserved.

Animals↗
PubMed2005

C-kit expression in germinoma: an immunohistochemistry-based study.

In our immunohistochemical study of 25 human primary intracranial germinomas and germinomas with syncytiotrophoblastic giant cells (STGC), we stained the same sections for c-kit and placental alkaline phosphatase (PLAP). Immunohistochemical expression was graded using a semi-quantitative scoring system where 3+ =51-75%, and 4+ =76-100%. Of the 25 cases, 7 (28%) were graded 3+ and 18 (72%) 4+ for c-kit; 8 (32%) were 3+ or 4+ for PLAP. All 3 cases negative for PLAP-staining were strongly positive and all embryonal carcinomas, immature teratomas, and yolk sac tumors were negative for c-kit staining. The soluble isoform of c-kit (s-kit) is reportedly detectable in cerebral spinal fluid of patients with germinomas and germinomas with STGC. C-kit and s-kit may be powerful tumor markers for germinomas with or without STGC.

Adolescent↗
PubMed2005

Experimental autoimmune uveitis induced by immunization with retinal pigment epithelium-specific 65-kDa protein peptides.

PURPOSE: To investigate the pathogenic potential and sites of retinal pigment epithelium-specific 65-kDa protein (RPE65) for inducing experimental autoimmune uveitis (EAU) in Lewis rats. METHODS: Twenty-six peptides were chemically synthesized based on the amino acid sequences of human RPE65. These peptides spanned the entire RPE65 sequence. Each peptide was injected into a footpad and the peritoneum of Lewis rats. The eyes were examined by slit-lamp biomicroscopy, and the findings were correlated with the histological findings. The serum antibody titer and lymphocyte reactivity against each peptide was also determined by enzyme-liked immunosorbent assay (ELISA) and lymphocyte proliferation assay, respectively. RESULTS: Active immunization of rats resulted in the induction of EAU with 14 (3 severe and 11 mild) of the 26 peptides. The clinical course of the EAU was similar to that induced by the injection of retinal antigens such as S-antigen or inter-photoreceptor retinoid binding protein (IRBP). However, the histopathologic changes differed from the EAU induced by these retinal antigens. The inflammation was induced mainly from the retinal pigment epithelium (RPE) and the choroid, while the retina was relatively well-preserved except for some granulomatous changes adjacent to the RPE. CONCLUSIONS: Active immunization with peptides making up RPE65 will induce EAU. RPE65 has multiple EAU-inducing sites for Lewis rats.

Animals↗
PubMed2005

Removal of retinal indocyanine green dye by autologous serum irrigation in macular hole surgery.

PURPOSE: To investigate the efficacy of autologous serum irrigation for removal of retinal indocyanine green (ICG) dye used to visualize the internal limiting membrane (ILM) in macular hole surgery. METHODS: Eighteen consecutive eyes of 16 patients with macular holes underwent vitrectomy and ILM peeling using ICG solution. Nine of 18 eyes underwent intravitreal autologous serum irrigation before completion of the surgery to remove residual ICG dye in the retina. The main outcome measures were postoperative visual acuity, macular hole status, retinal pigment epithelial changes, and time course of ICG dye fading from the retina with or without intravitreal autologous serum irrigation. RESULTS: No significant difference was noted in the improvement of visual acuity between the two groups. An abnormal pigment epithelial change was seen in one eye without serum application. ICG dye disappeared from the retina within an average of 6.1 months after surgery without serum and 2.4 months after surgery with serum (P < 0.01). CONCLUSIONS: Autologous serum irrigated in the vitreous cavity just before completion of macular hole surgery can help remove ICG dye used in surgery. The application was simple and safe and significantly shortened the period of residual retinal ICG staining.

Adult↗
PubMed2005

Comparative clinical study of the anti-emetic effects of oral ramosetron and injected granisetron in patients with malignant glioma undergoing ACNU chemotherapy.

The effectiveness of ramosetron tablets and granisetron injection was compared for reducing the frequency of nausea, vomiting, and anorexia in patients with malignant glioma undergoing ACNU chemotherapy. Patients with malignant glioma to be treated with ACNU chemotherapy were randomly assigned to receive oral ramosetron (20 patients) or intravenous granisetron (19 patients) prior to ACNU injection. Gastrointestinal toxicity within 48 hours of ACNU injection was compared to that in patients who had received ACNU chemotherapy with dopamine D2 receptor-blocker as a historical control group. Within 24 hours of the administration of ACNU, 15 of the 20 patients treated with ramosetron and 16 of the 19 treated with granisetron were nausea-free, and 14 of the former and 14 of the latter regained their normal appetite. There was no significant difference in the anti-emetic effects. Ten of the 17 controls experienced no vomiting within 6 hours of the injection of ACNU, five were nausea-free within 24 hours, and two retained their normal appetite within 24 hours. Oral ramosetron has the same anti-anorectic and anti-emetic effects as intravenous granisetron. Ramosetron tablets are less expensive and are easy to take, so should be on the list of first-choice anti-emetic drugs for patients treated with ACNU chemotherapy.

Adult↗
PubMed2005

Effect of surgical removal on survival and quality of life in patients with supratentorial glioblastoma.

The relationship between the extent of tumor resection and the progression-free survival, overall survival, and quality of life was evaluated retrospectively in 105 consecutive adult patients with supratentorial hemispheric glioblastoma not primarily involving the basal ganglia, thalamus, or hypothalamus. All patients underwent multidisciplinary treatment including tumor removal and postoperative adjuvant therapy in prospective randomized trials designed to test several chemotherapy regimens. Magnetic resonance imaging with contrast medium was used to determine the extent of tumor resection. Gross total resection (GTR) was performed in 35 patients (33%), partial resection (PR) in 57 (54%), and biopsy in 13 (12%). Univariate and multivariate analysis was performed to assess the prognostic relevance of the extent of resection. The Karnofsky performance status (KPS) improved from 78% to 83% in the GTR group. The difference was not statistically significant. There was no significant change in the PR (from 70% to 72%) and the biopsy groups (from 64% to 62%). Progression- free survival was significantly longer in the GTR group (median survival time [MST] 10.3 months) than in the PR (MST 5.2 months) and the biopsy groups (MST 3.6 months). The overall survival was significantly longer in the GTR group (MST 20 months) than in the PR (MST 14.2 months) and the biopsy groups (MST 8.3 months). The difference in survival between the PR and the biopsy groups was not statistically significant. GTR prolongs the survival of patients with glioblastoma compared to PR or biopsy.

Adolescent↗
PubMed2005

Effect of oral colestimide on the elimination of high-dose methotrexate in patients with primary central nervous system lymphoma--case report.

Delayed methotrexate (MTX) elimination occurred in two patients with primary central nervous system lymphoma undergoing high-dose MTX treatment. Oral administration of the anion exchange resin colestimide, which binds MTX effectively in vitro, effectively accelerated MTX elimination. Colestimide probably interrupts the enterohepatic circulation, and is a potential oral antidote to MTX toxicity.

Administration, Oral↗
PubMed2004

Oncolysis by viral replication and inhibition of angiogenesis by a replication-conditional herpes simplex virus that expresses mouse endostatin.

BACKGROUND: In preclinical models, infection of tumors by oncolytic strains of herpes simplex virus 1 (HSV-1) resulted in the destruction of tumor cells by viral replication and release of progeny virion that infected and destroyed adjacent tumor cells. However, complete tumor regression was rarely observed. METHODS: To augment the antitumor effect of viral oncolysis, a replication conditional HSV-1 mutant (HSV-Endo) was constructed in which the murine endostatin gene was incorporated into the HSV-1 genome. RESULTS: Replication of HSV-Endo effectively destroyed several colon carcinoma cell lines in vitro. Secretion of endostatin by HSV-Endo-infected HT29 human colon carcinoma cells was confirmed by Western blot analysis. The secreted endostatin was biologically active as assessed in a chick chorioallantoic membrane assay. Importantly, endostatin production at the site of viral replication did not inhibit viral replication. Direct injection of HSV-Endo into flank tumors caused tumor destruction, and some of the HSV-Endo-treated flank tumors completely sloughed. Immunohistochemical staining of the tumors revealed a decreased number of blood vessels in the HSV-Endo-treated group versus the control group. CONCLUSIONS: The oncolytic HSV-1 mutant HSV-Endo provided a two-pronged therapy; namely, inhibition of angiogenesis and direct tumor cell destruction by viral replication.

Allantois↗