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Biomedical subjects

T Tanimoto

Publications and source records attributed to T Tanimoto.

At least 91 records · Page 5Linked to original sources

Isolation and characterization of di- and tri-mannosyl-cyclomaltoheptaoses (beta-cyclodextrins) produced by reverse action of alpha-mannosidase from jack bean.

Di- and tri-mannosyl-cyclomaltoheptaoses (beta-cyclodextrins, beta CDs), which were synthesized together with monomannosyl-beta CD in a large-scale production by reverse action of alpha-mannosidase from jack bean, were isolated and purified by HPLC. The structures of seven isomers of di-mannosyl-beta CD and six isomers of tri-mannosyl-beta CD were elucidated by FABMS and NMR spectroscopy, and by enzymatic methods.

Chromatography, High Pressure Liquid↗

Retention behavior of positional isomers of disubstituted cyclomalto-oligosaccharide (cyclodextrin) derivatives on an ODS column.

The correlation between hydrophobic effects and structures of three and four positional isomers of 6(1),6n-di-O-triphenylmethyl (trityl)- or 6(1),6n-di-O-tert.- butyldimethylsilyl (tert.-BuMe2Si)-cyclomaltohexaoses (cG6s, alpha-cyclodextrin) (n = 2-4), -cyclomaltoheptaoses (cG7s, beta-cyclodextrin) (n = 2-4), and -cyclomaltooctaoses (cG8s, gamma-cyclodextrin) (n = 2-5) on an ODS column are discussed. Cyclodextrins with two hydrophobic-substituted groups bonded to hydroxyl groups tended to show low retention of positional isomers in which the binding positions of the two substituted groups on the cyclodextrin ring were far apart from each other.

Carbohydrate Conformation↗

Suppressive effect of vagal afferents on the activity of the trigeminal spinal neurons related to the jaw-opening reflex in rats: involvement of the endogenous opioid system.

The purpose of the present study is to test the hypothesis that via the endogenous pain control system, vagal afferent input modulates the activity of the trigeminal spinal nucleus oralis (TSNO) related to the tooth pulp (TP)-evoked jaw-opening reflex (JOR). Extracellular single-unit recordings were made from 36 TSNO units responding to TP electrical stimulation with a constant temporal relationship to a digastric electromyogram (dEMG) signal in 26 pentobarbital-anesthetized rats. The activity of 36 TSNO neurons and the amplitude of the dEMG increased proportionally during 1.0-3.5 times the threshold for JOR. Some of these neurons (4 out of 5) were also excited by chemical stimulation (bradykinin, 1-2 microl, 1 mM) of TP. In 31 out of 36 TSNO neurons (86%), their activities during tooth pulp stimulation were suppressed by conditioning stimulation of the right vagus nerve. The suppressive effect of vagal afferent stimulation occurred at conditioning-test intervals of 20-150 ms after the onset of the stimulation, and its maximal suppressive effect occurred at approximately 50 ms. The mean time course of this suppressive effect paralleled that of the dEMG. After administration of naloxone (0.5 and 1.0 mg/kg, i.v.), an opiate receptor blocker, the suppressive effect on the activity of TSNO neurons (6 out of 8) was significantly attenuated at the conditioning-test interval of 50 ms compared to the control (p < 0.01). These results suggested that vagal afferent input inhibits nociceptive transmission in the TSNO related to TP-evoked JOR and this inhibitory effect may occur via the endogenous opioid system in rats.

Afferent Pathways↗

A critical role for IL-18 in the proliferation and activation of NK1.1+ CD3- cells.

Like IL-12, IFN-gamma-inducing factor/IL-18 has been shown to stimulate T cells for IFN-gamma production and growth promotion. Considering the NK-stimulatory capacity of IL-12, we investigated the effect of IL-18 on NK lineage cells. A CD4- CD8- surface Ig- Ia- fraction of freshly prepared C57BL/6 spleen cells proliferated strikingly in response to combinations of IL-12 + IL-18 or IL-2 + IL-18, but not to the individual cytokines or IL-2 + IL-12. Cells proliferating in response to IL-2 + IL-18 were NK1.1+ CD3-, whereas IL-12 + IL-18-responsive cells were NK1.1- CD3-. Restimulation of the former cells with IL-12 + IL-18 or the latter cells with IL-2 + IL-18 resulted in the generation of NK1.1- CD3- or NK1.1+ CD3- cells, respectively. Moreover, a NK1.1+ CD3- CD4- CD8- surface Ig- Ia- population isolated from spleen cells was found to form NK1.1+ CD3- or NK1.1- CD3- blasts by stimulation with IL-2 + IL-18 or IL-12 + IL-18, respectively, and the NK1.1 positivity on these blasts was again reversed after restimulation with an alternative combined stimulus. Both types of blasts produced enormously large amounts of IFN-gamma in response to IL-12 + IL-18 and exhibited strikingly high levels of NK activity. These results indicate that IL-18 plays an obligatory role in inducing proliferation and activation of NK1.1+ CD3- CD4- CD8- cells and that the expression of the NK1.1 marker is reversible, depending on the cytokine used for stimulation in combination with IL-18.

Animals↗

Interleukin-18/interferon-gamma-inducing factor, a novel cytokine, up-regulates ICAM-1 (CD54) expression in KG-1 cells.

Intercellular adhesion molecule-1 (ICAM-1, CD54) is a membrane glycoprotein and a member of the immunoglobulin superfamily. It plays a central role in cell to cell-mediated immune responses and is a ligand for leukocyte function-associated antigen-1 (LFA-1). We report here that a newly discovered cytokine, interferon-gamma-inducing factor (IGIF) [H. Okamura et al. (1995) Nature 378, 88] recently proposed to be designated as IL-18, selectively up-regulates ICAM-1 expression in KG-1 cells, a human myelomonocytic cell line, in which IL-18 also enhances interferon-gamma production. IL-18 induced heterotypic aggregation between KG-1 and Peer T cells, which was blocked by anti-ICAM-1 and/or LFA-1 antibodies. Anti-interferon-gamma antibody did not block the IL-18-induced up-regulation of ICAM-1 on KG-1 cells. These results thus show that IGIF/IL-18, enhances ICAM-1 expression in KG-1 cells in an interferon-gamma-independent pathway, up-regulates ICAM-1 functions, and that IL-18 might play a potential role in immunoregulation by mediating immune cell infiltration into the tissues.

Cell Line↗

Growth patterns in various macroscopic types of noninvasive intramucosal colorectal carcinoma with special reference to apoptosis and cell proliferation.

PURPOSE: Apoptotic cell death and cell proliferation play important roles in the histogenesis and development of colorectal carcinoma. The aim of this study was to examine the relationship between apoptosis and cell proliferation in various macroscopic types of intramucosal colorectal carcinoma in relation to the expression of p53 and bcl-2. METHODS: One hundred forty cases with endoscopically or surgically resected intramucosal colorectal carcinoma were studied. There were 57 cases of polypoid-type carcinomas, 55 cases of superficial-type carcinomas, and 28 cases of granular-type, laterally spreading tumors. Polypoid-type carcinomas were pedunculated, subpedunculated, or sessile polyps. Superficial-type carcinomas were flat lesions with a smooth, even surface. Granular-type, laterally spreading tumors were superficially spreading lesions with aggregates of nodules and a granular surface. Apoptotic cells were identified by the in situ DNA nick end labeling method. Ki-67, p53, and bcl-2 expression were examined immunohistochemically. RESULTS: The superficial-type carcinoma apoptotic index (30.9 percent) was significantly lower than that of polypoid-type carcinoma (54.4 percent) and granular-type, laterally spreading tumor (60.7 percent). The superficial-type carcinoma proliferative index (67.3 percent) was significantly higher than that of polypoid-type carcinoma (42.1 percent) and granular-type, laterally spreading tumor (28.6 percent). In superficial-type carcinomas the proliferative index in p53-positive carcinomas was significantly higher, and the apoptotic index was higher in carcinomas with a lower proliferative index. There was no significant difference in apoptotic index, proliferative index, or p53 protein overexpression between de novo carcinomas and those that had arisen in precursor adenomas. CONCLUSIONS: The pattern of cell death and proliferation may vary with different macroscopic types of intramucosal colorectal carcinoma. Superficial-type colorectal carcinomas especially demonstrate diminished apoptosis and increased cell proliferation. This may be useful in understanding their biologic behavior.

Apoptosis↗

Excitatory mechanism of veratridine on slowly adapting pulmonary stretch receptors in anesthetized rabbits.

The excitatory effects of veratridine on slowly adapting pulmonary stretch receptors (SARs) were studied before and after administration of ouabain (a Na+-K+ ATPase inhibitor) in anesthetized, artificially ventilated rabbits after vagus nerve section. Administration of veratridine (40 microg/kg) stimulated SAR activity but did not significantly alter tracheal pressure. Administration of ouabain (50 microg/kg) initially stimulated SAR activity during both inflation and deflation, but after 20 min, two different types of SAR responses were observed; one became silent at the peak, of inflation only, and the other maintained excitatory activity during both inflation and deflation phases. Veratridine usually inhibited SAR activity in ouabain-treated animals, irrespective of the difference of ouabain effects. These results suggest that veratridine-induced stimulation of SARs is closely related to the change in the Na+ ion gradient, which is regulated by Na+ pump activity.

Anesthesia↗

Cloning and expression of a single-chain Fv fragment specific for the human interleukin 18 receptor.

We have recently reported the successful purification and characterization of the human interleukin 18 (IL-18) receptor (R) using a monoclonal antibody (MAb) of the IgM kappa class (117-10C) after immunizing mice with cells of the Hodgkin's disease-derived cell line L428. This antibody is specific for the human IL-18R and inhibits the bioactivity of IL-18. Here we report on the polymerase chain reaction (PCR)-assisted cloning and sequencing of cDNAs encoding the variable regions of the light and heavy chains of 117-10C. We expressed the antibody in the form of a single-chain Fv fragment (scFv) in Chinese Hamster Ovary (CHO) cells and purified it from culture supernatants by chromatography. The purified scFv has an affinity for IL-18R of 5.6 x 10(8) M(-1), whereas 117-10C binds to the receptor with an affinity constant of 3.6 x 10(9) M(-1). Since 117-10C is of the IgM class, it is expected to be in the pentamer form and should theoretically therefore bind IL-18R with 10 times the affinity of the single-chain fragment may explain the difference in the affinity constants for the two molecules. The inhibitory efficiency of 117-10C was found to be 6-fold that of scFv in an interferon gamma (IFN-gamma)-inducing assay on the IL-18-responsive cell line KG-1. In conclusion, we have produced a single-chain fragment of a murine anti-human IL-18R antibody that is as potent at binding IL-18 as the parent antibody, and may be useful in neutralizing the cytokine in human conditions associated with high production of IL-18.

Amino Acid Sequence↗

T-cell-rich B-cell lymphoma in a pig.

A case of multicentric lymphoma with a mixed cell population of large to small round cells with the same nuclear features in a pig was studied immunohistochemically. Neoplastic tissues were composed of 20-50% B-cell lymphoma cells with lambda-type light chain restriction, and 50-80% cluster of differentiation (CD)3+ T-cells. These findings were similar to those of human T-cell-rich B-cell lymphoma (TCRBCL). In addition, both immunoglobulin IgM and IgG were detected in the cytoplasm of the identical lymphoma cell. This pattern of heavy chain expression appeared to be due to maturational arrest in cellular development at the point of heavy chain class switching, as occurs in biclonal gammopathy in human lymphoid malignancy. This case as TCRBCL containing two types of heavy chains with light chain restriction (IgM-lambda and IgG-lambda) appears to be the first of its kind reported in the English literature for either pigs or domestic animals.

Animals↗

Eosinophilic proliferative pylephlebitis in the liver of Japanese beef cattle with fascioliasis.

Intrahepatic pylephlebitis was detected in 17 Japanese beef cattle. Grossly, the intrahepatic vessels in the caudate lobe and/or in the periphery of the other hepatic lobes were thickened and protruded above the lobar surface. The vessel lumina were packed with white to red, waste thread-like contents. A few immature flukes were found in the bile ducts in 3 of the 7 cases with biliary thickening. Foci of hepatic necrosis and hemorrhage were scattered around the thickened vessels in 8 cases. Histologically, the interlobular veins were thickened due to severe intimal hyperplasia with endothelial proliferation and eosinophilic accumulation and medial hypertrophy, accompanied by fibrosis and eosinophilic infiltration in the portal areas. Hepatic tissues with necrosis and hemorrhage were surrounded by eosinophils and histiocytes including a granulomatous reaction. One immature fluke was detected in one of these regions of necrosis. Immunoperoxidase staining revealed that the small fluke, Kupffer cells, and histiocytes in the liver of all cases were positively stained with anti-Japanese Fasciola sp. antiserum. Enzyme-linked immunosorbent assay of the sera of 15 cases revealed that all were positive for the anti-Fasciola antibody. On the basis of these findings, the present cases were regarded as an atypical form of fascioliasis, characterized by eosinophilic proliferative pylephlebitis of the liver.

Animals↗

C-Fos-like immunoreactivity in the upper cervical spinal dorsal horn neurons following noxious chemical stimulation of the nasal mucosa in pentobarbital-anesthetized rats.

Noxious chemical stimulation of the rat nasal mucosa with mustard oil induces the expression of Fos-like immunoreactivity in trigeminal and other brain stem neurons which contribute to upper airway protective reflexes such as sneezing, coughing and apnea. To examine the role of nociceptive processing in the upper cervical spinal cord, we investigated the Fos-like immunoreactivity of the brainstem and upper cervical spinal cord following the injection of mustard oil (10 microl of 10%) into the nasal mucosa of pentobarbital anesthetized rats. Two hours after the application of mustard oil, numerous Fos-immunoreactive neurons were found in the mediolateral end of the C1 and dorsolateral division of the C2. The mean numbers of the Fos-immunoreactive neurons in the laminae I and II of the ipsilateral first and second spinal segments were significantly greater than in the control (vehicle treated) rats. There were no significant differences in the mean number of Fos-immunoreactive neurons in the contralateral C1 between the mustard oil and vehicle-treated rats. These results suggest that the C1-C2 dorsal horn neurons process the nociceptive information from nasal mucosa as well as other areas innervated by the trigeminal nerves, and that ethmoidal nerves may contribute to the exclusive conveyance of nociceptive information.

Adjuvants, Anesthesia↗

Influence of interindividual variability of aldose reductase protein content on polyol-pathway metabolites and redox state in erythrocytes in diabetic patients.

OBJECTIVE: To clarify the influence of interindividual difference in the level of aldose reductase on the polyol pathway-related metabolism in diabetic patients. RESEARCH DESIGN AND METHODS: The enzyme protein content was determined by a two-site enzyme-linked immunosorbent assay using monoclonal and polyclonal antibodies to recombinant human aldose reductase in erythrocytes from 35 diabetic patients and 11 healthy volunteers. Patients were stratified into two groups by the median of aldose reductase content, and the erythrocyte sorbitol level, the fructose level, and the lactate-to-pyruvate ratio were compared between the two groups. We also examined the correlation of the enzyme content with these metabolic parameters. RESULTS: The group of patients whose enzyme content was above the median showed a significant increase in the levels of sorbitol (34.7 +/- 4.9 vs. 20.4 +/- 2.0 nmol/g Hb, P < 0.05) and fructose (99.8 +/- 17.2 vs. 45.9 +/- 4.6 nmol/g Hb, P < 0.05), along with an elevated lactate-to-pyruvate ratio (28.6 +/- 6.1 vs. 11.7 +/- 1.2, P < 0.05), compared with patients with low enzyme levels. The aldose reductase content in erythrocytes was well correlated with its activity, and there was a significant correlation between the enzyme content and the erythrocyte sorbitol (r = 0.58, P < 0.001) or fructose (r = 0.57, P < 0.001) levels as well as between the enzyme level and the lactate-to-pyruvate ratio (r = 0.38, P < 0.05). CONCLUSIONS: These results suggest that the interindividual variability of aldose reductase content may contribute tangibly to the polyol-pathway flux and cytoplasmic redox alteration in diabetic patients.

Aldehyde Reductase↗

Inhibitory activity to protein prenylation and antifungal activity of zaragozic acid D3, a potent inhibitor of squalene synthase produced by the fungus, Mollisia sp. SANK 10294.

Recently we found novel zaragozic acids (ZAs), F-10863A (zaragozic acid D3, ZAD3), B, C and D in the culture broth of the fungus Mollisia sp. SANK 10294 as potent inhibitors of squalene synthase. There are several other enzymes that use farnesylpyrophosphate as their substrate. Among them we chose farnesyl-protein transferase and examined whether ZAD3 and F-10863B inhibit this enzyme's activity. ZAD3 and F-10863B inhibited farnesyl-protein transferase with IC50 values of 0.60 and 3.7 microM, respectively. They also inhibited geranylgeranyl-protein transferase at similar concentrations. In addition, they exhibited potent antifungal activity.

Alkyl and Aryl Transferases↗

[Potassium Sucrose Octa Sulfate Reference Standard (Control 961) of National Institute of Health Sciences].

The raw material of potassium sucrose octa sulfate was examined for the preparation of the "Potassium Sucrose Octa Sulfate Reference Standard (Control 961)". Analytical data obtained were as follows: infrared spectrum, the same as that of the Potassium Sucrose Octa Sulfate Reference Standard (Control 901); high-performance liquid chromatography, one impurity was detected; water content, 8.1%; assay of sucrose octa sulfate, 99.6%. Based on the above results, the raw material was authorized to be the Potassium Sucrose Octa Sulfate Reference Standard of the National Institute of Health Sciences.

Government Agencies↗

[Thrombin Reference Standard (Control 961) of National Institute of Health Sciences].

The "Thrombin Reference Standard (Control 961)" of National Institute of Health Sciences was prepared. The precision of filling into ampoule was about 1% as C.V. The content of a-thrombin was about 87%. The thrombin potency of the standard material was assayed against the Thrombin Reference Standard (Control 8710) according to the method of JP XIII and the potency was 1033 +/- 59 unit/ampoule. From the results, the potency of the proposed material for Thrombin Reference Standard was defined as 1,030 units per ampoule.

Government Agencies↗

[Kallidinogenase Reference Standard (Control 971) of National Institute of Health Sciences].

The "Kallidinogenase Reference Standard (Control 971)" of National Institute of Health Sciences was prepared. The kallidinogenase potency of the standard material was assayed against the 2nd Kallidinogenase Reference Standard (Control 854) by the enzyme assay method using H-D-valyl-L-leucyl-L-arginine-p-nitro-anilide as the substrate. The potency of the Kallidinogenase Reference Standard material thus obtained was defined as 119 unit per ampoule.

Government Agencies↗

[Retinol Acetate Reference Standard (Control 971) and Retinol Palmitate Reference Standard (Control 971) of National Institute of Health Sciences].

The "Retinol Acetate Reference Standard (Control 971)" and "Retinol Palmitate Reference Standard (Control 971)" of National Institute of Health Sciences using the assay of vitamin A ester were prepared. The proposed materials were evaluated in collaboration with four laboratories. Analytical data obtained were as follows. 1) The purities of retinol acetate and retinol palmitate measured by HPLC were 99.9 +/- 0.06% and 94.5 +/- 0.06%, respectively. 2) ultraviolet spectrum of retinol acetate and retinol palmitate showed the lambda max at 326-327 nm. 3) The difference in relative extinction of retinol acetate and retinol palmitate at 300 nm, 310 nm, 320 nm, 330 nm, 340 nm and 350 nm are within the range provided in JPXIII. 4) The contents of retinol acetate and retinol palmitate were 52,000 IU/g and 52,200 IU/g, respectively. Based on the above results, these proposed materials were authorized to be the Reference Standards of the National Institute of Health Sciences.

Diterpenes↗

[Cholecalciferol Reference Standard (Control 971) of National Institute of Health Sciences].

The raw material for cholecalciferol was examined for preparation of the "Cholecalciferol Reference Standard (Control 971)". Analytical data obtained were as follows: melting point, 83.8 degrees C; UV and infrared spectra, the same as those for JP Cholecalciferol Reference Standard (Control 945), respectively; specific absorbance at 265 nm, E1 cm 1% = 485; optical rotation, [alpha]D20 = +107.4 degrees; thin-layer chromatography and high-performance liquid chromatography (HPLC), no impurity was detected; assay, 98.9% by HPLC. Based on the above results, the raw material was authorized as the Cholecalciferol Reference Standard (Control 971) of National Institute of Health Science.

Chemical Phenomena↗