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H Okamoto

Publications and source records attributed to H Okamoto.

At least 217 records · Page 12Linked to original sources
PubMed2000

Role of cGMP versus 20-HETE in the vasodilator response to nitric oxide in rat cerebral arteries.

This study examined the response to nitric oxide (NO) in rat middle cerebral arteries (MCA). NO donors increased the activity of a 205-pS K(+) channel recorded from vascular smooth muscle (VSM) cells isolated from MCA 10-fold. Blockade of guanylyl cyclase activity with 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ, 10(-5) M) did not alter the effect of NO on this channel. In contrast, adding 20-hydroxyeicosatetraenoic acid (20-HETE) to the bath (10(-7) M) abolished the response to NO. NO donors also increased the diameter of serotonin-preconstricted MCA to 85% of control. Blockade of K(+) channels with iberiotoxin or a high-K(+) medium reduced this response by 50%. ODQ (10(-5) M) reduced this response by 47 +/- 3%, whereas preventing the fall of 20-HETE levels reduced the response by 59 +/- 2% (n = 5). Blockade of both pathways eliminated the response to NO donors. These results indicate that activation of K(+) channels contributes 50% to vasodilator response to NO in rat MCA. This is mediated by a fall in 20-HETE levels rather than a rise in cGMP levels or a direct effect of NO.

Animals↗
PubMed2000

Reciprocal functions of liver tumor cells and endothelial cells. Involvement of endothelial cell migration and tumor cell proliferation at a primary site in distant metastasis.

BACKGROUND: The mechanism by which tumor cells interact with endothelial cells at the primary site in metastasis remains obscure. MATERIALS AND METHODS: To disclose the precise mechanisms and processes of metastasis and angiogenesis, we investigated the interactions of endothelial cells (CPAE; calf pulmonary arterial endothelial cells) with two mouse liver tumor cell lines, G-5, a highly metastatic clone, and G-1, a poorly metastatic clone, based on the difference in their angiogenic activities in vivo at a primary site. RESULTS: G-5 cell cultured conditioned medium (CM) promoted migration of endothelial cells more than did G-1 cell CM, in migration assay using modified Boyden chambers. Anti-basic FGF antibody inhibited G-5-induced endothelial cell migration. Furthermore, endothelial cells stimulated proliferation of G-5 cells more than that of G-1 cells in coculture assay using Transwell chambers (pore size; 0.4 microm). Pretreated endothelial cells with bFGF enhanced tumor cell proliferation, suggesting the ability of activated endothelial cells to support tumor growth. In addition, incubation with endothelial cell CM also improved the proliferative activity of G-5 cells more than that of G-1 cells in a concentration-dependent fashion, indicating production and secretion of liver tumor cell growth substance by endothelial cells. CONCLUSION: These results provide evidence that liver tumor cells stimulate endothelial cell migration and migrated endothelial cells facilitate liver tumor cell proliferation. Tumor growth at a primary site may initially be dependent on migrated endothelial cells rather than vascularization or blood nutrient supply. This bi-directional paracrine relationship between liver tumor cells and endothelial cells may influence their metastatic ability.

Animals↗
PubMed2000

Pharmacokinetic interactions between HIV-1 protease inhibitors in rats: study on combinations of two kinds of HIV-1 protease inhibitors.

The drug interactions between four human immune deficiency virus (HIV-1) protease inhibitors have been characterized by in-vitro metabolic studies using rat liver microsomal fractions and in-vivo oral administration. In this study, a new HPLC analytical method developed by us was used for the simultaneous determination of saquinavir and nelfinavir in rat plasma and microsomes. The metabolic clearance rates (Vmax/Km) of saquinavir, nelfinavir, and indinavir were 170.9 +/- 10.9, 126.1 +/- 4-4, and 73.0 +/- 2.0 microL min(-1) (mg protein)(-1), respectively. Ritonavir was the strongest inhibitor with inhibition constants (Ki) of 1.64 microM for saquinavir, 0.95 microM for indinavir, and 1.01 microM for nelfinavir. Nelfinavir was the second strongest inhibitor with Ki's of 2.35 microM for saquinavir and 2.14 microM for indinavir. Indinavir was the third strongest inhibitor with Ki's of 2.76 microM for nelfinavir and 3.55 microM for saquinavir. Saquinavir was the weakest inhibitor for the other three HIV- 1 protease inhibitors. After oral co-administration in combination with another HIV-1 protease inhibitor, the AUCs of saquinavir, indinavir, and nelfinavir were significantly increased compared with mono-treatment. The AUCs of saquinavir were increased about 10.1-, 3.1- and 45.9-fold in the presence of indinavir, nelfinavir and ritonavir, respectively. The AUCs of indinavir were increased about 6.8-, 5.9- and 9.4-fold in the presence of nelfinavir, saquinavir and ritonavir, respectively. The AUCs of nelfinavir were increased about 2.2-, 6.6- and 8.5-fold in the presence of indinavir, saquinavir and ritonavir, respectively. The in-vivo effects observed after co-administration of two kinds of HIV-1 protease inhibitor were not always expected from in-vitro data, suggesting the presence of other interaction processes besides metabolism in the liver. These results provide useful information for the treatment of AIDS patients receiving combination therapy with two HIV-1 protease inhibitors.

Animals↗
PubMed2000

Tissue-Specific expression of rat kininogen mRNAs.

To characterize the local kallikrein-kinin system, tissue distribution of mRNAs for kininogens, precursor proteins of kinins, such as high-molecular-weight (H-), low-molecular-weight (L-) and T-kininogens, were studied in the rat by means of reverse-transcription polymerase chain reaction (RT-PCR) using a fluorophore Cy5-labeled 5'-primer. High levels of these three kininogen mRNAs were present in the liver. Relatively high levels of H-kininogen mRNA were also detected in the skin, lung, kidney, and testis in a descending order, whereas L-kininogen mRNA was detectable in the lung and brain, but not in the kidney, skin, testis, heart, adrenal gland, or skeletal muscle. T-Kininogen mRNA was present in these tissues, except for skeletal muscle. These findings suggest that the expression of each kininogen mRNA is regulated by the tissue-dependent mechanisms which is closely associated with functions of the kallikrein-kinin system in the tissue.

Animals↗
PubMed2000

Amino acids and peptides. XXXV. Facile preparation of p-nitroanilide analogs by the solid-phase method.

p-Nitroanilides of amino acids and peptides are widely used as the chromogenic substrates for the determination of the activity of proteolytic enzymes. However, the preparation of a p-nitroanilide is not easy, in part due to the low nucleophilicity of the amino group of p-nitroaniline. A facile preparation of p-nitroanilide analog by the solid-phase method was investigated. 5-Amino-2-nitrobenzoic acid (Anb5,2) was used instead of p-nitroaniline (pNA) for preparation of p-nitroanilide analogs. Anb5,2 was introduced on a p-methylbenzhydrylamine resin without protection of the amino group of Anb5,2 by the 2-(H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) method in the presence of p-dimethylaminopyridine. The coupling reaction of a Nalpha-,NG-protected arginine with a Anb5,2-resin was difficult to achieve by common coupling methods (such as the carbodiimide and diphenylphosphoryl azide methods), but the phosphoryl chloride method was relatively successful. Synthetic benzoyl-Arg-Anb5,2-NH2 and benzoyl-Arg-pNA were hydrolyzed by trypsin and the both reaction mixtures exhibited same spectroscopic characteristics. H-D-Val-Leu-Arg-Anb5,2-NH2, an analog of human urine kallikrein substrate, was readily prepared by the solid-phase method. H-Arg-Anb5,2-OH and H-D-Val-Leu-Arg-Anb5,2-OH were also synthesized on a Wang resin by the solid-phase method. The aqueous solubility of these free-carboxyl materials was better than those of the corresponding amide analogs. 4-Amino-3-nitrobenzoic acid (Anb4,3) was also introduced on the p-methybenzhydrylamine resin, but the resulting H-Anb4,3-resin did not react with Nalpha,NG-protected arginine by any of the coupling methods.

Amino Acids↗
PubMed2000

The effects of adsorbed water on tensile strength and Young's modulus of moldings determined by means of a three-point bending method.

Young's moduli (E) of three representative tableting excipients and their mix powders were measured for compressed rectangular beam specimens over a range of porosities using a three-point bending technique. We also examined the effects of the amount of water adsorbed on the tensile strength of these specimens. The maximal tensile strength (sigma(max)) decreased with increasing water vapor adsorption for microcrystalline cellulose (MCC) and mixed powders of lactose and MCC. Sigma(max) increased with increasing compression stress and specimen weight for all samples. Sigma(max) of an alpha-lactose and cornstarch mixture with a ratio of 7:3 showed a large value. Young's modulus (E) and the crushing energy (CE) of MCC were larger than those of the other samples. Young's modulus of specimens decreased as the proportion of alpha-lactose increased. Disintegration time (DT) of tablets comprised of lactose and MCC mixture was much faster than those of tablets comprised of individual powders. This appeared to demonstrate the effect of MCC swelling on the disintegration time of the tablet. The disintegration time of the lactose/cornstarch series increased only when Young's modulus increased sharply.

Adsorption↗
PubMed2000

[Effect of mixing of fine carrier particles on dry powder inhalation property of salbutamol sulfate (SS)].

The most commonly used formulations for dry powder inhalations are binary ordered mixes composed of micronized drugs and coarse carriers. An optimal dry powder aerosol formulation should possess an optimal inhalation property and a good flow property. These characteristics are especially important for a multidose dry powder inheler (DPI). In the present study, model powder blend were prepared consisting of synthesized sugar (different particle sized isomalt; IM-PF, IM-FS, IM-F) as a carrier and micronized salbutamol sulfate (SS). These ordered mixtures were aerosolized by the multidose JAGO DPI (SkyePharma AG) and in vitro deposition properties (fine particle fraction, FPF) were evaluated by a twin impinger (TI) at a flow rate of 60 l/min. The separation property between SS and carrier particles was investigated by the centrifuge method and air jet sieve (AJS) method. It was found that FPF decreased with increasing carrier particle size. However, a large carrier particle possesses a good flow property. Therefore, the effect of mixing of fine carrier particles (IM-PF) into the large carrier particles (IM-FS) on dry powder inhalation property was investigated. When the proportion of IM-PF (fine carrier) increase from 0% to 25% of the total carrier powder blend, the FPF also increases from 16.7% to 38.9%. It is concluded that the effect of mixing of fine carrier particles might be a suitable method for improving the dry powder inhalation properties.

Administration, Inhalation↗
PubMed2000

A novel activating mutation in the thyrotropin receptor gene in an autonomously functioning thyroid nodule developed by a Japanese patient.

OBJECTIVE: A number of activating mutations of the thyrotropin receptor (TSHR) have been found in autonomously functioning thyroid nodules (AFTNs) in European patients. We aimed to study TSHR mutation in AFTNs in Japanese patients because no TSHR activating mutation has been found by previous incomplete studies. DESIGN: A typical AFTN developed in a 69-year-old Japanese woman was studied. METHODS: The entire exon 10 of the TSHR cDNA was sequenced. Functional studies were done by site-directed mutagenesis and transfection of a mutant construct into COS-7 cells. RESULTS: We identified a novel heterozygous TSHR gene mutation, Leu512-->Arg (L512R; CTG-->CCG), from the AFTN. The mutation was not detected in the adjacent normal thyroid tissue. COS-7 cells transfected with L512R mutant TSHR expression vector exhibited a 3.3-fold increase in basal cAMP level compared with that of cells transfected with wild-type TSHR DNA, confirming that the mutation was the direct cause of the AFTN. TSHR activating mutations involving the third transmembrane helix reported to date are S505R/N and V509A as well as L512R. An in vitro site-directed mutagenesis study encompassing residues 505-513 revealed that mutations involving residues other than these three did not show constitutive activation. CONCLUSION: This is the first TSHR activating mutation found in a Japanese patient, although true prevalence of TSHR activating mutations in AFTNs developed in Japanese patients remains to be elucidated. In addition, functional studies suggested that amino acid residues in the third transmembrane helix maintaining inactive conformation of the TSHR seem to be located on the same surface of the alpha-helix, possibly making interhelical bonds with another helix.

Aged↗
PubMed2000

N-hydroxy-4-(4-chlorophenyl)thiazole-2(3H)-thione as a photochemical hydroxyl-radical source: photochemistry and oxidative damage of DNA (strand breaks) and 2'-deoxyguanosine (8-oxodG formation).

On irradiation of N-hydroxythiazole-2(3H)-thione 3 at 300 nm, the photoproducts disulfide 4, bisthiazole 5 and thiazole 6 are formed. During this photolysis, hydroxyl radicals are released, which have been detected by spin trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), coupled with electron paramagnetic resonance spectroscopy. In the presence of supercoiled pBR322 DNA, irradiation of thiazolethione 3 induces strand breaks through the photogenerated hydroxyl-radicals, as confirmed by control experiment with the hydroxyl-radical scavenger isopropanol. Singlet oxygen appears not to be involved, as attested by the lack of a D2O isotope effect. During the photoreaction of thiazolethione 3 in the presence of 2'-deoxyguanosine (dG), the latter is photooxidized (ca 10% conversion after 2 h of irradiation) to the 7,8-dihydro-8-oxo-2'-deoxyguanosine as the main oxidation product. The dG conversion levels off after complete consumption of thiazolethione 3 and is suppressed by the addition of the hydroxyl-radical scavenger 2,6-di-tert-butylcresol or DMPO. Since the photoproducts 4-6 are ineffective as sensitizers for the photooxidation of dG and DNA, the hydroxyl radicals released in the photolysis of thiazolethione 3 are the oxidizing species of DNA and dG. These results suggest that the thiazolethione 3 may serve as a novel and effective photochemical hydroxyl-radical source for photobiological studies.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Response to combined modality treatment in a five-year survivor of extensive small cell lung cancer with severe complications.

We present a rare case of a five-year survivor of small cell lung cancer with severe complications who responded to combined modality treatment. Prior to initial chemotherapy, he experienced severe complications including sepsis, pneumonia, ileus, and a performance status of 4. He was treated with an ileus tube and IVH, and was managed by mechanical ventilation for four days. After his general condition improved, he received combination chemotherapy of carboplatin, with the target area under the plasma concentration versus the time curve (AUC) of 5 mg x min/ml day 1, and etoposide (80 mg/m2) on days 1, 2, 3 for four courses, and complete remission (CR) was obtained. Six months later, systemic relapse occurred, but he achieved complete remission again with nine courses of CODE (cisplatin, vincristine, adriamycin, and etoposide) chemotherapy and sequential chest radiotherapy. Five years after the initial chemotherapy, the patient is alive and disease free.

Carcinoma, Small Cell↗
PubMed2000

Relationship between suicide and holidays.

Employing the vital statistics from January 1, 1979 to December 31, 1994 in Hokkaido Prefecture, Japan, we investigated the relationship between suicide (ICD 9 code, El15) and days of the week. In one day 1.97 males and 0.98 females committed suicide on average. On Saturdays the number of suicides per day was the smallest. On Mondays it was the highest. When the days were classified into (1) a holiday, (2) the day before a holiday, (3) the day after a holiday (4) the day both before and after a holiday and (5) others, the rate of suicide was the lowest in the days before a holiday. In the days after a holiday, however, the rate was the highest. The same tendency was also noted when the subjects were classified into several subgroups from the viewpoint of ages, seasons or calendar years. The time relation of holidays seemed to have something to do with the intention to commit suicide.

Chi-Square Distribution↗
PubMed2000

Recurrent follicular and lichenoid papules of sarcoidosis.

We describe a 62-year-old Japanese woman who exhibited recurrent follicular lichenoid lesions of sarcoidosis. The skin lesions appeared all over the surface of the body without any other organ involvement, and spontaneously regressed within 1 year. Two years later, the lesions recurred on the trunk, especially in the intertriginous areas such as the submammary areas and in fatty folds of the abdomen, and on the thighs and upper arms, with the appearance of uveitis of the right eye. Histological examinations showed that small epithelioid cell granulomas were localized in the perifollicular areas. The present case was characterized by a unique distribution of follicular lichenoid eruptions, which are rare manifestations of sarcoidosis and recurrence of the lesions.

Biopsy↗
PubMed2000

[Recent topics in chemotherapy for elderly patients with lung cancer].

With the prolongation of life expectancy in Japan, lung cancer is increasing not only in the elderly but also in poor-risk patients who can not undergo standard chemotherapy. Because survival benefits from chemotherapy are clearly expected in patients with small-cell lung cancer (SCLC), standard chemotherapy should be established for the elderly as well as for poor-risk patients with SCLC. We recently reported that the combination of AUC-based carboplatin and a standard dose of intravenous etoposide was an active and relatively nontoxic regimen for elderly patients with SCLC (J Clin Oncol 17: 3540-3545, 1999). Had chemotherapy with concurrent chest irradiation been used for patients with limited disease (LD), better survival might have been achieved in this study. However, Pignon et al. reported that combined chemoradiotherapy in elderly patients with LD-SCLC is a possible poor prognostic factor in their meta-analysis. A recent randomized controlled clinical trial has shown that vinorelbine monotherapy contributed to longer survival in elderly patients with advanced non-small-cell lung cancer (NSCLC), compared to best supportive care. Several retrospective studies have shown that cisplatin can be safely and effectively administered to elderly patients who are eligible for protocol treatment. However, there have been no randomized trials indicating that cisplatin-based combination chemotherapy improves survival in elderly patients with advanced NSCLC, compared to single-agent chemotherapy. Similarly, the role of combined chemoradiotherapy remains controversial in elderly patients with locally advanced NSCLC. Thus, standard therapies proven to be beneficial to non-elderly patients with lung cancer have not always been proven to be beneficial to elderly patients. In order to solve these difficult problems, phase III studies are warranted in elderly or poor-risk patients with lung cancer. Moreover, new agents with relatively low toxicities recently approved in Japan should be applied in clinical trials for the elderly or poor-risk patients with lung cancer.

Administration, Oral↗
PubMed2000

Transfusion-associated graft-versus-host disease with transfusion practice in cardiac surgery.

BACKGROUND: Transfusion-associated graft-versus-host disease (TA-GVHD) in immunocompetent patients has still been underdiagnosed and underreported. Risk of TA-GVHD caused by transfusion practice in cardiac surgery should be appropriately recognized. METHODS: The correlation of TA-GVHD with transfusion practice in cardiac surgery was analyzed from our 17-year clinical experience. We retrospectively reviewed 2,686 consecutive adult patients who underwent cardiac surgery between 1980 and 1996. Classified according to transfusion practice, 847 patients (32%) received nonirradiated fresh homologous whole blood (mean per patient, 5+/-2 units) with or without other blood components; 592 patients (22%) nonirradiated stored RBCs older than 7 days (4+/-2), and 551 patients (21%) received irradiated homologous blood including, fresh whole blood (2+/-1), RBCs (4+/-1), and PCs (8+/-3), respectively. The remaining 696 patients (25%), did not require homologous transfusion. RESULTS: Four of 847 patients who received nonirradiated fresh homologous whole blood (< or =48 hours after donation) developed TA-GVHD. TA-GVHD did not occur in other patients. CONCLUSIONS: Our local experience demonstrates the incidence of TA-GVHD in patients who received fresh homologous whole blood in cardiac surgery was much higher, compared with previous reports. This result suggests that the frequency of TA-GVHD is nearly similar to the value calculated from the proportion of HLA haplotypes in the population.

Adult↗
PubMed2000

[A case of pulmonary cavernous hemangioma: immunohistological examination revealed its endothelial cell origin].

A 29-year-old woman was referred to our hospital for an abnormal shadow on chest roentgenogram. She had no symptom but its shadow was pointed out about 20 years ago. Chest CT scan showed a sharply demarcated homogenous mass measured 10 x 10 mm in the S4 segment. The tumor was resected with video-assisted thoracoscopic surgery under CT-guided marking wire inserted. Microscopic examination suspected cavernous hemangioma. Immunohistological staining demonstrated most lining cells of the cavernous structure stained positively for von Willebrand factor antibody, which suggests that this tumor was associated with endothelium. Then we decided that this tumor was pulmonary cavernous hemangioma.

Adult↗