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Biomedical subjects

H Nishino

Publications and source records attributed to H Nishino.

At least 19 recordsLinked to original sources

Molecular cloning and expression of a mouse thiamin pyrophosphokinase cDNA.

Thiamin pyrophosphokinase (EC 2.7.6.2) catalyzes the pyrophosphorylation of thiamin with adenosine 5'-triphosphate to form thiamin pyrophosphate. A mouse thiamin pyrophosphokinase cDNA clone (mTPK1) was isolated using a combination of mouse expressed sequence tag database analysis, a two-step polymerase chain reaction procedure, and functional complementation screening with a Saccharomyces cerevisiae thiamin pyrophosphokinase-deficient mutant (thi80). The predicted protein contained 243 amino acid residues with a calculated molecular weight of 27,068. When the intact mTPK1 open reading frame was expressed as a glutathione S-transferase fusion protein in Escherichia coli lacking thiamin pyrophosphokinase, marked enzyme activity was detected in the bacterial cells. The corresponding 2.5-kilobase pair mRNA was expressed in a tissue-dependent manner and was found at relatively high levels in the kidney and liver, indicating that the mode of expression of mTPK1 genes differs with cell type. The expression of mTPK1 genes in cultured mouse neuroblastoma and normal liver cells was unaffected by the thiamin concentration in the medium (10 microM versus 3.0 nM). This is the first report on identification of the primary sequence for mammalian thiamin pyrophosphokinase.

Amino Acid Sequence

Anti-tumor promoting activity of polyphenols from Cowania mexicana and Coleogyne ramosissima.

Chemical investigation on polyphenol-rich fractions of Cowania mexicana and Coleogyne ramosissima (Rosaceae) which showed significant inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), has led to the characterization of 10 compounds including C-glucosidic ellagitannin monomers and dimers from the former plant, and 17 polyphenols including flavonoid glycosides from the latter. The effects of individual components and their analogues with related structures on the TPA-induced EBV-EA activation were then evaluated. Among the compounds isolated from C. mexicana, two C-glucosidic ellagitannins, alienanin B and stenophyllanin A and a nitrile glucoside (lithospermoside), and among the constituents from C. ramosissima, two flavonoid glycosides, isorhamnetin 3-0-beta-D-glucoside and narcissin were revealed to possess strong inhibitory effects on EVB-EA activation, the potencies of which were either comparable to or stronger than that of a green tea polyphenol, (-)-epigallocatechin gallate. These polyphenols except for nitrile glucoside, which was not tested owing to an insufficient amount, were also found to exhibit anti-tumor promoting activity in two-stage mouse skin carcinogenesis using 7,12-dimethylbenz[a]anthracene (DMBA) and TPA.

9,10-Dimethyl-1,2-benzanthracene

Inhibitory effects of monoacylated 2-O-beta-galactosylglycerols on Epstein-Barr virus activation: the significant role of the hexanoyl chain.

Three series of monoacyl-2-O-beta-D-galactosylglycerols bearing an acyl chain of varying length, from C4 to C10, were studied due to their antitumor promoting effects on the activation of the Epstein-Barr virus early antigen (EBV-EA), such activation being induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). This study indicates that it is more the length of the acyl chain that is important for the activity, six carbon atoms resulting in maximum effect, rather than the position of the ester function and the nature of the sugar (galactose or glucose).

Antigens, Viral

Anti-tumor-promoting effects of phenylpropanoids on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis.

In our joint project in the search for anti-tumor promoters from natural plant sources, we carried out a primary screening of 12 phenylpropanoids isolated from Boronia pinnata Sm. (Rutaceae) by examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All tested compounds in this study showed inhibitory activity against the EBV activation even at 1 x 10 mol ratio without any cytotoxicity. Among 12 phenylpropanoids tested, boropinal-C (1), boropinol-A (5), boropinol-C (9) and 3-(3'-methoxy-4'-prenyloxy)phenyl-1-propene (10), all having a 4'-(3-methylbut-2-enyloxy) group, a so-called prenyloxy group, showed more potent activities. Furthermore, 3-(3'-methoxy-4'-prenyloxy)phenyl-1-propene (10) also exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. This investigation indicated that certain phenylpropanoids might be valuable anti-tumor promoters.

Animals

Inhibitory effect of Epstein-Barr virus activation by Citrus fruits, a cancer chemopreventor.

To search useful compounds in Citrus fruit for cancer chemoprevention, we carried out a primary screening of extracts of fruit peels and seeds from 78 species of the genus Citrus and those from two Fortunella and one Poncirus species, which were closely related to the genus Citrus. These Citrus extracts inhibited the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) as a useful screening method for anti-tumor promoters. Our results indicated that Citrus containing substances may be inhibit susceptibility factors involved in the events leading to the development of cancer.

Animals

Anti-tumor-promoting effects of 8-substituted 7-methoxycoumarins on Epstein-Barr virus activation assay.

In a search for anti-tumor-promoting agents, we carried out a primary screening of twenty-nine 8-substituted and four 6-substituted derivatives of 7-methoxycoumarins isolated from plants of the Murraya and/or Citrus species (Rutaceae), examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. This investigation indicated that the prenyl (3-methyl-2-butenyl) or 2-hydroxy-3-methylbutyl (or butenyl) unit as an isoprenoid moiety at C-8 on the 7-methoxycoumarin nucleus plays an important role in the anti-tumor-promoting activity. Some of the 8-substituted 7-methoxycoumarins isolated from Murraya species, murrangatin (7), minumicrolin (10) and chloticol (18), were found to significantly inhibit EBV-EA activation, and preserved the high viability of Raji cells, suggesting that 7, 10 and 18 might be valuable anti-tumor-promoting agents.

Antineoplastic Agents

An antitumor promoter from Moringa oleifera Lam.

In the course of studies on the isolation of bioactive compounds from Philippine plants, the seeds of Moringa oleifera Lam. were examined and from the ethanol extract were isolated the new O-ethyl-4-(alpha-L-rhamnosyloxy)benzyl carbamate (1) together with seven known compounds, 4(alpha-L-rhamnosyloxy)-benzyl isothiocyanate (2), niazimicin (3), niazirin (4), beta-sitosterol (5), glycerol-1-(9-octadecanoate) (6), 3-O-(6'-O-oleoyl-beta-D-glucopyranosyl)-beta-sitosterol (7), and beta-sitosterol-3-O-beta-D-glucopyranoside (8). Four of the isolates (2, 3, 7, and 8), which were obtained in relatively good yields, were tested for their potential antitumor promoting activity using an in vitro assay which tested their inhibitory effects on Epstein-Barr virus-early antigen (EBV-EA) activation in Raji cells induced by the tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA). All the tested compounds showed inhibitory activity against EBV-EA activation, with compounds 2, 3 and 8 having shown very significant activities. Based on the in vitro results, niazimicin (3) was further subjected to in vivo test and found to have potent antitumor promoting activity in the two-stage carcinogenesis in mouse skin using 7,12-dimethylbenz(a)anthracene (DMBA) as initiator and TPA as tumor promoter. From these results, niazimicin (3) is proposed to be a potent chemo-preventive agent in chemical carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene

The Big Blue(R) transgenic mouse mutation detection assay: the mutation pattern of sectored mutant plaques.

There are mutational artifacts in the Big Blue(R) assay and it is important to characterize the source and nature of these mutations. Differences were reported in the mutation patterns of a small sample of 23 sectored and 91 circular mutant plaques derived from skin using the Big Blue(R) transgenic mouse mutation detection system [G. R. Stuart, N.J. Gorelick, J.L. Andrews, J.G. de Boer, B.W. Glickman, The genetic analysis of lacI mutations in sectored plaques from Big Blue transgenic mice, Environ. Mol. Mutagen 28 (1996) 385-392.]. We have extended these observations by analyzing 46 sectored and 224 circular mutant plaques derived from seven tissues. The frequency of sectored mutant plaques is estimated to be 16% with no significant variation with tissue type. However, the patterns of mutation for sectored mutants and mouse-derived mutations differed significantly (p=0.04). Base substitutions in sectored mutant plaques do not show the asymmetries found in circular mutants consistent with integration of a GC rich transgene into the AT rich mammalian genome. Sectored mutants have mutation patterns consistent with a mixture of mouse, in vitro and Escherichia coli-derived mutations. Data on the relative frequencies of different mutant plaque morphologies suggests that overlapped plaques are substantially contaminated by sectored plaques at recommended plating densities.

Animals

Guideline of surgical management based on diffusion of descending necrotizing mediastinitis.

BACKGROUND: Descending necrotizing mediastinitis resulting from oropharyngeal abscess, is a serious, life-threatening infection. Exisiting strategies for surgical management, such as transcervical mediastinal drainage or aggressive thoracotomic drainage, remain controversial. METHODS: Four patients, (three males and one female) were treated for descending necrotizing mediastinitis resulting from oropharyngeal infection. Two had peritonsillar abscesses, while the others experienced dental abscess and submaxillaritis. Descending necrotizing mediastinitis received its classification according to the degree of diffusion of infection diagnosed by computed tomography. Mediastinitis in two cases, (Localized descending necrotizing mediastinitis-Type I), was localized to the upper mediastinal space above the carina. In the others, infection extended to the lower anterior mediastinum (Diffuse descending necrotizing mediastinitis-Type IIA), and to both anterior and posterior lower mediastinum (Diffuse descending necrotizing mediastinitis-Type IIB). The spread of infection to the pleural cavity occurred in three cases. RESULTS: The surgical outcome concerning each of the patients was successful. Radical cervicotomy (unilateral in three patients, bilateral in the other) in conjunction with mechanical ventilation with continuous postoperative positive airway pressure, was performed in all cases. Tracheostomy was established in three patients and pharyngostomy in two. The two descending necrotizing mediastinitis-Type I cases were successfully managed with transcervical mediastinal drainage. The descending necrotizing mediastinitis-Type IIA case received treatment through transcervicotomy and anterior mediastinal drainage through a subxiphoidal incision. The patient with descending necrotizing mediastinitis-Type IIB required posterior mediastinal drainage through a right standard thoracotomy followed by left minimal thoracotomy. CONCLUSIONS: The mediastinal infection, the extent of which has been accurately determined by computed tomograms, necessitates radical cervicotomy followed by pleuromediastinal drainage. Situations where infection has spread to posterior medisatinum, particularly when it reaches in the level of the carina (descending necrotizing mediastinitis-type I), may not always require aggressive mediastinal drainage. In comparison, diffuse descending necrotizing mediastinitis-Type IIB demands complete mediastinal drainage with debridement via thoracotomy. Subxiphoidal mediastinal drainage without sternotomy may provide adequate drainage in diffuse descending necrotizing mediastinitis-Type IIA.

Abscess

A case of laryngeal neurinoma with neurofibromatosis 2.

We present a case of a laryngeal neurinoma in a patient with neurofibromatosis 2. A 39-year-old man presented to our hospital with multiple complaints including progressive bilateral hearing loss, dizziness, dyspnea, dysphagia, and a 9-year history of right lower leg weakness. Magnetic resonance imaging demonstrated multiple lesions including bilateral cerebellopontine angle tumors, a foremen magnum tumor, multiple tumors of the spinal cord, a laryngeal tumor, and several retrocervical tumors. Fiberoptic laryngoscopy revealed a large submucosal supraglottic tumor. The laryngeal tumor was visualized through microlaryngoscopy and excised with a KTP laser directed through a quartz fiber.

Adult

Inhibitory effect of some triterpenes from cacti on 32Pi-incorporation into phospholipids of HeLa cells promoted by 12-O-tetradecanoylphorbol-13-acetate.

Seventeen triterpenes isolated from cacti and the 10 derivatives were examined for the inhibition of tumor promoter-induced effects in vitro, such as stimulation of 32Pi-incorporation into phospholipids of cultured cells. Betulinic acid (1), cochalic acid (15), erythrodiol (16), oleanolic acid (21) and queretaroic acid (24) inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated 32Pi-incorporation into phospholipids of the cultured cells.

Animals

Chemoenzymatic synthesis and antitumor promoting activity of 6'- and 3-esters of 2-O-beta-D-glucosylglycerol.

Through a simple chemoenzymatic approach 6'- and 3-esters of 2-O-beta-D-glucosylglycerol 1, with short-medium length fatty acid acyl chains, were prepared. The study of their in vitro antitumor promoting effect on Epstein-Barr virus early antigen (EBV-EA) activation, in comparison with that of the 1-esters previously described, confirms the significant activity of such monoacylated glycoglycerolipid analogues and establishes for the glucose series that the 1-substitution and the hexanoyl chain are the proper structural features for the maximum activity.

Anticarcinogenic Agents

Cancer chemopreventive agents (antitumor-promoters) from Ajuga decumbens.

Sixteen compounds (1-16) isolated from the flowering whole plant of Ajuga decumbens have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) induction by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), as a primary screening test for antitumor-promoters (potential cancer chemopreventive agents). Five compounds (6, 9, and 12-14) showed strong inhibitory effects on EBV-EA induction. Of these active compounds, two major constituents of this plant, cyasterone (6) and 8-acetylharpagide (13), showed potent antitumor-promoting activities on a mouse-skin in vivo two-stage carcinogenesis procedure, using 7, 12-dimethylbenz[a]anthracene as initiator and TPA as promoter. Further, compound 13 also exhibited potent chemopreventive activity in a mouse pulmonary tumor model.

4-Nitroquinoline-1-oxide

Anti-tumor-promoting rearranged abietane diterpenes from the leaves of Larix kaempferi.

Two novel rearranged abietane-type diterpene acids, karamatsuic acid (1) and larikaempferic acid (2) were isolated as their corresponding methyl esters, 1a and 2a, from the leaves of Larix kaempferi (Lamb.) Carr. Their structures were established as 9,10 alpha-epoxy-9,10-seco-abieta-8,11,13-trien-18-oic acid and 9 alpha,13 alpha-epoxy-8-oxo-9(8-->7)abeo-7 beta H-abietan-18-oic acid, respectively, by spectral evidence. Compounds 1a, 2a and 12,15-dihydroxydehydroabietic acid (3) exhibited potent inhibitory effects against 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) activation in Raji cells.

Animals

[Congenital ventricular diverticulum in a neonate: anesthetic considerations].

Congenital diverticulum of the ventricle is a rare cardiac malformation and the reports of its surgical repair are scarce. We experienced anesthesia for a neonate with an isolated congenital left ventricular diverticulum diagnosed in utero. A male infant presented with ventricular arrhythmias and congestive heart failure. At 9 days of life the resection of the diverticulum was performed under moderately hypothermic cardio-pulmonary bypass (CPB) Major anesthetic considerations include the possible life-threatening arrhythmias, cardiac failure due to diverticulum and cardiac dysfunction after resection. Premature ventricular contractions were noted before CPB but greatly decreased under anesthesia. The operation was performed safely and arrhythmias disappeared completely after resection. Intra- and post-operative course was uneventful without any sign of cardiac dysfunction.

Anesthesia, Inhalation

[Follow-up study on effects of height velocity and puberty onset on biochemical markers of bone turnover].

In order to clarify the factors which affect bone metabolism at a young age, we investigated the relationships among the change of biochemical markers of bone turnover, the height velocity (HV) and puberty onset in healthy Japanese children. One hundred and twelve children (61 boys and 51 girls) were recruited at the fourth grade level in the elementary school (9 years old) and followed for 6 years. Serum bone specific alkaline phosphatase (B-ALP), serum tartrate-resistant acid phosphatase (TR-ACP), urine hydroxyproline (Hyp) and urine calcium (Ca) were measured as the biochemical markers of bone turnover. Bone mineral density of calcaneus was also measured by ultrasound method at the first grade (12 years old) and the third grade (14 years old) of junior high school. Heights and weights of all subjects were measured every April and the HV were calculated between each year. Puberty onset was defined as the time when pubic hair appeared in boys and as the time when menarche started in girls by self-administered questionnaire. All the biochemical markers of bone metabolism except for urine Ca had a significant positive relationship with HV. The values of the markers were highest of the time when the HV was maximum. In girls, the values of the biochemical markers remained high before menarche and then decreased significantly within three years after menarche, suggesting that bone turnover changed rapidly from high turnover type to low turnover type after menarche. On the other hand, in boys, high turnover type remained for a few years after puberty onset. Bone mineral density of calcaneus by ultrasound method increased significantly in boys between the two years in junior high school, but the increase was unclear except for broadband ultrasound attenuation (BUA) in girls in the same period.

Acid Phosphatase

[Combined chemotherapy with low-dose cisplatin, tegafur and uracil for head and neck squamous cell carcinomas].

The mechanism for the effect of cisplatin (CDDP) as a modulator for 5-fluorouracil (5-FU) has already been described. The effective AUC of serum 5-FU concentration with oral administration of tegafur and uracil (UFT) has been revealed. We administered a dose of 200-600 mg/body of UFT orally every day, and 3.5-10 mg/m2 of CDDP by drip infusion 5 days a week. Hospitalized patients were administered these agents for 2-5 weeks. Eleven patients were enrolled, including 4 with untreated pharyngeal squamous cell carcinoma (SCC), 5 with locoregional recurrent SCC, and 2 with pulmonary multiple metastases. The mean age of the patients was 71 years, and all patients had a PS 3. Of the 4 patients with untreated pharyngeal SCC, PR was noted in 3 and NC in one, for a response rate of 75%. Of the 11 patients with locoregional recurrent and pulmonary metastatic SCC, PR was noted in only one patient for a response rate of 14%. Although on average these patients died of the primary disease 150 days after chemotherapy, 4 patients later showed an improved PS stage, and could were able to leave the hospital. These 4 patients could stay home with a PS 0 or PS 1 for an average of 133 days, and survived with the disease for an average of 240 days after chemotherapy. No side effects were observed in any patients. In side of the low response rate for locoregional recurrent and pulmonary metastatic SCC, the present therapy was thought to be useful from the viewpoint of the quality of life.

Administration, Oral

Inhibitory effects of dehydrozingerone and related compounds on 12-O-tetradecanoylphorbol-13-acetate induced Epstein-Barr virus early antigen activation.

Dehydrozingerone, 4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one, is half an analog of curcumin which is known to have anti-tumor activity. The anti-tumor promoting activity of dehydrozingerone was evaluated by determining the inhibitory effect on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The concentration needed for 50% inhibition of the tumor promotion (IC50) of dehydrozingerone was similar to that of curcumin. To elucidate the structure-activity relationship on the anti-tumor promoting activity, dehydrozingerone, curcumin, isoeugenol, which has no carbonyl group in the side chain, benzalacetone, which is the basic structure of dehydrozingerone, o-dehydrozingerone, which is the ortho-hydroxyl substituted compound of dehydrozingerone, and their related compounds were investigated using the in vitro short-term assay on TPA-induced EBV-EA activation. o-Dehydrozingerone showed the most potent inhibitory effect in a series of tested dehydrozingerone derivatives and their related monosubstituted benzalacetones. This suggests that the occupation at both ortho positions of the hydroxyl group enhances the anti-tumor promoting activity. Isoeugenol inhibited the tumor promoting activity at a concentration of about one-third of the IC50 of dehydrozingerone. This indicates that the carbonyl group in the side chain has a negative impact on the anti-tumor promoting activity. The inhibitory effects of the carbon-carbon bond in the side chain were studied using benzylacetone with a single bond, benzalacetone with a double bond and 4-phenyl-3-butyn-2-one with a triple bond. 4-Phenyl-3-butyn-2-one inhibited the most potent activity followed by benzalacetone and benzylacetone.

Anti-Inflammatory Agents, Non-Steroidal