Biomedical subjects

S Yano

Publications and source records attributed to S Yano.

At least 55 records · Page 3Linked to original sources

PubMed2002

Exacerbation of pulmonary lymphangioleiomyomatosis by exogenous oestrogen used for infertility treatment.

Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease that affects women in the reproductive years. It is occasionally associated with tuberous sclerosis, especially in the incomplete form. As it is likely that oestrogen plays a central role in disease progression, exogenous oestrogen will cause a deterioration in LAM. However, the early stage of this disease is easy to miss unless the physician is a specialist. Although there have been some reports in menopausal women given exogenous oestrogen for osteoporosis, this is the first report of pulmonary LAM caused by exogenous oestrogen used for the treatment of infertility.

Adult↗

PubMed2001

Unprecedented sugar-dependent in vivo antitumor activity of carbohydrate-pendant cis-diamminedichloroplatinum(II) complexes.

Eight carbohydrate-pendant platinum(II) complexes have been synthesized from carbohydrate-diamine conjugates. D-Glucose, D-mannose, D-galactose, D-xylose, and L-glucose are attached to the dichloroplatinum(II) moiety by 1,3- or 1,2-diaminopropane chelates through with an O-glycoside bond. All the carbohydrate moieties reduced the toxicity inherent with platinum(II) complexes.

Animals↗

PubMed2001

Stimulatory effects of centrally injected kainate and N-methyl-D-aspartate on gastric acid secretion in anesthetized rats.

The effects of N-methyl-D-aspartate (NMDA), kainate and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), ionotropic glutamate agonists, on gastric acid secretion were investigated in the continuously perfused stomach of anesthetized rats. The lateral ventricular (LV) injection of kainate (0.01-1 microg) or NMDA (0.3-3 microg) dose-dependently stimulated gastric acid secretion. AMPA (3-10 microg) also stimulated gastric acid secretion but the effect was very weak. Repeated injections of kainate (0.1 microg) or NMDA (1 microg), at least twice, stimulated gastric acid secretion to a similar degree. The effect of kainate (0.1 microg) was blocked by the kainate receptor antagonists, 6-cyano-7-nitroquinoxaline-2,3-dione disodium (3 microg, LV) and D-gamma-glutamylaminomethanesulfonic acid (30 microg, LV), but not by NMDA receptor antagonists. The effect of NMDA (10 microg) was blocked by (+/-)-3-(2-carboxypiperazin-4-yl)-1-propylphosphonic acid (10 microg, LV), a competitive NMDA receptor antagonist, and (+)-5-methyl-10,11-dihydro-5H-dibenzocyclo-hepten-5,10-imine hydrogen maleate (10 microg, LV), a non-competitive NMDA receptor antagonist, but not by kainate receptor antagonists. Moreover, the gastric acid secretion stimulated by kainate and NMDA were completely blocked by systemic atropine injection (1 mg/kg, i.v.) and vagotomy. These findings suggest that kainate and NMDA receptor mechanisms are independently involved in the central nervous system to control gastric acid secretion through vagus cholinergic activation.

Acetylcholine↗

PubMed2001

Interferon-alpha prevents selection of doxorubicin-resistant undifferentiated-androgen-insensitive metastatic human prostate cancer cells.

BACKGROUND: We determined whether treatment of metastatic prostate cancer cells with doxorubicin (DOX) and interferon-alpha (IFN-alpha) prevented the emergence of highly undifferentiated tumor cells. METHODS: The state of cell differentiation was determined by analysis of prostate-specific antigen (PSA), E-cadherin, keratin, and vimentin. RESULTS: Human prostate cancer LNCaP-LN3 cells growing in culture as multicell spheroids expressed higher levels of E-cadherin and E-cadherin-associated beta-catenin than LNCaP-LN3 cells growing as monolayers. Treatment of cells with DOX downregulated PSA, E-cadherin, and keratin, and upregulated expression of vimentin and vascular endothelial growth factor (VEGF) mRNA. While treatment of cells with IFN-alpha did not alter gene expression, the addition of IFN-alpha to cultures treated with DOX produced synergistic toxicity and abrogated the changes in gene expression observed in cells treated with DOX alone. CONCLUSIONS: Treatment with IFN-alpha and DOX should be further explored as a therapeutic strategy for androgen-insensitive prostate cancer.

Androgens↗

PubMed2001

Intravenously injected FK506 failed to inhibit hippocampal calcineurin.

FK506 (tacrolimus) is known as an inhibitor for calcineurin and is used in numerous research fields. It is not clear whether intravenously injected FK506 inhibits neuronal calcineurin. We measured the calcineurin activities of normal and postischemic rat hippocampi after intravenous injection of FK506 (3 mg/kg). Intravenously injected FK506 had no inhibitory effect on calcineurin activity in the hippocampi of normal and postischemic rats, whereas FK506 inhibited the calcineurin in vitro (purified enzyme, hippocampal homogenate, and hippocampal slice culture homogenate). Thus, it is considered that intravenously injected FK506 does not act on intraneuronal calcineurin and that several effects of FK506 are not due to the inhibition of neuronal calcineurin.

Animals↗

PubMed2001

Expression of angiopoietin-2 in human glioma cells and its role for angiogenesis.

In highly vascular malignant glioma, glioma cells themselves may express angiogenic factors and induce angiogenesis. Recent studies have shown that novel angiogenic factors, angiopoietin-1 (Ang1) and -2 (Ang2), play important roles in the modulation of vasculogenesis and angiogenesis. In this study, we determined Ang2 mRNA expression in cultured human malignant glioma cells (U105, U251, and U373 MG) by reverse transcriptase-PCR. Western blot analysis and immunocytochemical analysis with antihuman Ang2 antibody revealed that Ang2 protein was expressed and secreted by these cells. Furthermore, hypoxia increased the Ang2 protein level in cultured glioma cells. Serial sections of 32 human glioma tissues (14 glioblastomas, eight anaplastic astrocytomas, seven astrocytomas, and three pilocytic astrocytomas) were immunostained against Ang2, vascular endothelial growth factor, Tie2, von Willebrand factor, and alpha smooth muscle actin. The immunoreactivity of each angiogenic factor was higher in malignant gliomas than in low-grade gliomas. Ang2 protein was detected not only in endothelial cells but also in glioma cells, and its expression was prominent in both the area surrounding the necrosis and the periphery of glioblastomas. In the area surrounding necrosis, Ang2 was highly expressed and tumor vessels showed regression. In the tumor periphery, Ang2 was highly expressed and many small vessels stained positively for von Willebrand factor but not for alpha smooth muscle actin, suggesting angiogenesis. Statistical analysis revealed that the Ang2 expression was negatively correlated with vessel maturation in malignant gliomas and that vascular endothelial growth factor expression was positively correlated with vessel maturation in low-grade gliomas (P < 0.05). These results suggest that glioma cells themselves express Ang2 and that expression may be induced by hypoxic stimulation and may play a crucial role in the vessel maturation, angiogenesis, and vessel regression in malignant glioma.

Adolescent↗

PubMed2001

Association of arrhythmia and sudden death in macrocephaly-cutis marmorata telangiectatica congenita syndrome.

Macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC) constitutes a distinct entity characterized by prenatal overgrowth, macrosomia, hemihypertrophy, macrocephaly, nonobstructive hydrocephaly, frontal bossing, hypotonia, developmental delay, generalized or facial capillary malformation with upper philtral nevus flammeus and cutis marmorata, joint hypermobility, loose skin, toe syndactyly, and postaxial polydactyly. All but one of the cases reported previously had benign clinical courses without showing an increased risk of early infant death. We describe three additional cases with poor clinical outcomes including severe postnatal growth failure, intractable cardiac arrhythmia in two cases, and sudden infant death in two cases. Arrhythmia has not been described previously as one of the symptoms of M-CMCT. Patients with M-CMTC associated with severe postnatal growth failure and arrhythmia may constitute a distinct clinical subtype of M-CMTC with an increased risk of life-threatening episodes or sudden death. Recognizing this clinical subtype of M-CMTC is important to prevent these serious potential complications.

Abnormalities, Multiple↗

PubMed2001

Trinuclear Zn(II) and Cu(II) homo and heterotrimetallic complexes involving D-glucopyranosyl and biscarboxylate bridging ligands. A substrate binding model of xylose isomerases.

Reactions of MCl(2).nH(2)O with N,N'-bis(D-glucopyranosyl)-1,4,7-triazacyclononane ((D-Glc)(2)-tacn), which was formed from D-glucose and 1,4,7-triazacyclononane (tacn) in situ, afforded a series of mononuclear divalent metal complexes with two beta-D-glucopyranosyl moieties, [M((D-Glc)(2)-tacn)Cl]Cl (M = Zn (11), Cu (12), Ni (13), Co (14)). Complexes 11-14 were characterized by analytical and spectroscopic measurements and X-ray crystallography and were found to have a distorted octahedral M(II) center ligated by the pentacoordinate N-glycoside ligand, (beta-D-glucopyranosyl)(2)-tacn, and a chloride anion. Each D-glucose moiety is tethered to the metal center through the beta-N-glycosidic bond with tacn and additionally coordinated via the C-2 hydroxyl group, resulting in a lambda-gauche five-membered chelate ring. When L-rhamnose (6-deoxy-L-mannose) was used instead of D-glucose, the nickel(II) complex with two beta-L-rhamnopyranosyl moieties, [Ni((D-Man)(2)-tacn)(MeOH)]Cl(2) (15), was obtained and characterized by an X-ray analysis. Reactions of 11 (M = Zn) with [Zn(XDK)(H(2)O)] (21) or [Cu(XDK)(py)(2)] (22) (H(2)XDK = m-xylylenediamine bis(Kemp's triacid imide)) yielded homo and heterotrimetallic complexes formulated as [Zn(2)M'((D-Glc)(2)-tacn)(2)(XDK)]Cl(2) (M' = Zn (31), Cu (32)). The similar reactions of 12 (M = Cu) with complex 21 or 22 afforded [Cu(2)M'((D-Glc)(2)-tacn)(2)(XDK)]Cl(2) (M' = Cu (33), Zn (34)). An X-ray crystallographic study revealed that complexes 31 and 34 have either Zn(II)(3) or Cu(II)Zn(II)Cu(II) trimetallic centers bridged by two carboxylate groups of XDK and two D-glucopyranosyl residues. The M...M' separations are 3.418(3)-3.462(3) A (31) and 3.414(1)-3.460(1) A (34), and the M...M'...M angles are 155.18(8) degrees (31) and 161.56(6) degrees (34). The terminal metal ions are octahedrally coordinated by the (D-Glc)(2)-tacn ligand through three nitrogen atoms of tacn, two oxygen atoms of the C-2 hydroxyl groups of the carbohydrates, and a carboxylate oxygen atom of XDK ligand. The central metal ions sit in a distorted octahedral environment ligated by four oxygen atoms of the carbohydrate residues in the (D-Glc)(2)-tacn ligands and two carboxylate oxygen atoms of XDK. The deprotonated beta-D-glucopyranosyl unit at the C-2 hydroxyl group bridges the terminal and central ions with the C-2 mu-alkoxo group, with the C-1 N-glycosidic amino and the C-3 hydroxyl groups coordinating to each metal center. Complexes 31-34 are the first examples of metal complexes in which D-glucose units act as bridging ligands. These structures could be very useful substrate binding models of xylose or glucose isomerases, which promote D-glucose D-fructose isomerization by using divalent dimetallic centers bridged by a glutamate residue.

Aldose-Ketose Isomerases↗

PubMed2001

Substrate-dependent chemoselective aldose-aldose and aldose-ketose isomerizations of carbohydrates promoted by a combination of calcium ion and monoamines.

Epimerization of aldoses at C-2 has been extensively investigated by using various metal ions in conjunction with diamines, monoamines, and aminoalcohols. Aldoses are epimerized at C-2 by a combination of alkaline-earth or rare-earth metal ions (Ca(2+), Sr(2+), Pr(3+), or Ce(3+)) and such monoamines as triethylamine. In particular, the Ca(2+)-triethylamine system proved effective in promoting aldose-ketose isomerization as well as C-2 epimerization of aldoses. 13C NMR studies using D-(1-(13)C)glucose and D-(1-(13)C)galactose with the CaCl(2) system in CD(3)OD revealed that the C-2 epimerization proceeds via stereospecific rearrangement of the carbon skeleton, or 1,2-carbon shift, and ketose formation proceeds partially through an intramolecular hydrogen migration or 1,2-hydride shift and, in part, via an enediol intermediate. These simultaneous aldose-aldose and aldose-ketose isomerizations showed interesting substrate-dependent chemoselectivity. Whereas the mannose-type aldoses having 2,3-erythro configuration (D-mannose, D-lyxose, and D-ribose) showed considerable resistance to both the C-2 epimerization and the aldose-ketose isomerization, the glucose-type sugars having 2,3-threo and 3,4-threo configurations, D-glucose and D-xylose, are mainly epimerized at C-2 and those having the 2,3-threo and 3,4-erythro configurations, D-galactose and D-arabinose, were mostly isomerized into 2-ketoses. These features are of potential interest in relevance to biomimic sugar transformations by metal ions.

Aldose-Ketose Isomerases↗

PubMed2001

The effectiveness of an immobilization device in conformal radiotherapy for lung tumor: reduction of respiratory tumor movement and evaluation of the daily setup accuracy.

PURPOSE: To evaluate the daily setup accuracy and the reduction of respiratory tumor movement using a body frame in conformal therapy for solitary lung tumor. METHODS AND MATERIALS: Eighteen patients with a solitary lung tumor underwent conformal therapy using a body frame. The body shell of the frame was shaped to the patient's body contour. The respiratory tumor movement was estimated using fluoroscopy, and if it was greater than 5 mm, pressure was applied to the patient's abdomen with the goal of minimizing tumor movement. CT images were then obtained, and a treatment planning was made. A total dose of 40 or 48 Gy was delivered in 4 fractions. Portal films were obtained at each treatment, and the field displacements between them and the simulation films were measured for daily setup errors. The patients were repositioned if the setup error was greater than 3 mm. Correlations were analyzed between patient characteristics and the tumor movement, or the tumor movement reduction and the daily setup errors. RESULTS: Respiratory tumor movement ranged from 0 to 20 mm (mean 7.7 mm). The abdominal press reduced the tumor movement significantly from a range of 8 to 20 mm to a range of 2 to 11 mm (p = 0.0002). Daily setup errors were within 5 mm in 90%, 100%, and 93% of all verifications in left-right, anterior-posterior, and cranio-caudal directions, respectively. Patient repositioning was performed in 25% of all treatments. No significant correlation was detected between patient characteristics and tumor movement, tumor movement reduction, and the daily setup errors. CONCLUSIONS: The abdominal press was successful in reducing the respiratory tumor movement. Daily setup accuracy using the body frame was acceptable. Verification should be performed at each treatment in hypofractionated conformal therapy.

Adolescent↗

PubMed2001

Promotion of radiation-induced formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by nitro 5-deazaflavin derivatives.

6-Nitro- and 8-nitro-5-deazaflavin derivatives have been found to enhance prominently the radiation-induced formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) at the expense of formation of 2,6-diamino-4-hydroxy-5-formamidopyrimidine nucleosides (FapydGuo) both in deaerated and in N(2)O saturated aqueous 2'-deoxyguanosine solutions. The radiosensitizing capacity of a 9-nitro-5-deazflavin derivative was observed only in the N(2)O saturated aqueous solutions.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2001

Sugar-pendant diamines.

A set of 1,3-propanediamine derivatives connected to carbohydrates (5) has been prepared in four steps from peracetylated sugar and 1,3-dibromo-2-propanol in 60-73% yields. D-Glucose, D-mannose, D-galactose, D-xylose, D-ribose, and maltose are utilized as sugar molecules in this work. The diamine moiety was connected to the C1 carbon of the glycopyranose ring via an O-glycoside bond. All of the anomeric configurations and sugar puckering conformations, except in the D-maltose derivative, were determined by X-ray crystallography of the diazido or dibromo precursors. While glycosidation of peracetylated galactopyranose with 1,3-dibromo-2-propanol in the presence of boron trifluoride afforded both anomers, the neighboring group participation of the 2-acetoxy group yielded a single anomer for the other substrates. This method has been used to synthesize a library of sugar-pendant diamines including an OH-protected derivative (6), and an N,N'-diisopropyl-substituted derivative (7). A similar series of reactions using 2,3-dibromo-1-propanol gave ethylenediamine-type derivatives (11), and bis(bromomethyl)bis(hydroxymethyl)methane (12) gave bisglucose-pendant derivatives (16).

Carbohydrate Sequence↗

PubMed2001

Stimulatory effects of nitric oxide donors on gastric acid secretion in isolated mouse stomach.

We previously reported on the stimulatory role of endogenous nitric oxide (NO) in gastric acid secretion. In the present study, we investigated the effects of NO donors on acid secretion in isolated mouse stomach. Nitroprusside (100 microM(-1) x mM) inhibited the gastric acid secretion induced by histamine (500 microM) in a concentration-dependent manner. In addition, nitroprusside abolished the acid secretion induced by bethanechol (100 microM) and by electrical stimulation (10 Hz) of the vagus nerve. On the other hand, nitroprusside, 75 microM, which did not affect the acid secretion induced by histamine, itself elicited an increase in acid secretion. The acid secretion induced by 75 microM nitroprusside was inhibited by 10 microM famotidine, a histamine H2 receptor antagonist. These results suggest that NO donors at high doses act on gastric parietal cells, resulting in inhibition of the stimulated acid secretion, and, at lower doses, facilitate histamine release from histamine-containing cells, leading to the increased acid secretion.

Animals↗

PubMed2001

A strong association between HLA-DR9 and gelatin allergy in the Japanese population.

The frequency of HLA class I and II phenotypes was determined among 23 patients with positive gelatin IgE, eight of whom developed anaphylaxis, 18 patients who did not have gelatin IgE but who experienced non-immediate reactions after exposure to gelatin. HLA-DR9, which is unique to Orientals, was present in 56.5% of the gelatin IgE positive patients, as compared to control population frequency of 24% (P < 0.002). In the non-immediate reaction group, who did not generate IgE, phenotype distribution resembled controls. HLA-DR9 positive individuals have a relative risk of 4.1 for developing gelatin allergy with positive IgE.

Anaphylaxis↗

PubMed2001

Humanized anti-ganglioside GM2 antibody is effective to induce antibody-dependent cell-mediated cytotoxicity in mononuclear cells from lung cancer patients.

Ganglioside GM2 is one of the major gangliosides expressed on the cell surface of human tumors including lung cancer. We have previously reported that a mouse-human chimeric monoclonal antibody (mAb), KM966, against GM2 promotes the lysis of lung cancer cells by human blood mononuclear cells (MNC) of healthy donors. In this study, we examined antibody-dependent cell-mediated cytotoxicity (ADCC) of MNC, using KM966 mAb and its humanized counterpart, KM8969, in 16 lung cancer patients and 18 control patients. The ADCC activity was assessed by 4-h (51)Cr release from GM2 positive SBC-3 small cell lung cancer cells. MNC from lung cancer patients exhibited similar ADCC activity to those from control patients when KM966 and KM8969 were used as mAb. Moreover, effective ADCC activity was observed even in MNC from advanced lung cancer patients. These observations suggest the potential activity of humanized anti-GM2 mAb (KM8969), as well as chimeric KM966, in biological therapy for lung cancer patients.

Aged↗

PubMed2001

Serotonin induces the expression of tissue factor and plasminogen activator inhibitor-1 in cultured rat aortic endothelial cells.

Serotonin (5-hydroxytryptamine, or 5-HT), released from activated platelets, not only accelerates aggregation of platelets but also is known to promote mitosis, migration, and contraction of vascular smooth muscle cells (VSMCs). These effects are considered to contribute to thrombus formation and atherosclerosis. The aim of this study was to investigate the effects of 5-HT on the expressions of coagulative and fibrinolytic factors in rat aortic endothelial cells. Endothelial cells were stimulated with various concentrations of 5-HT (0.1 approximately 10 microM), and the expressions of tissue factor (TF), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1), and tissue-type plasminogen activator (TPA) messenger RNAs (mRNAs) were evaluated by Northern blot analysis. The activities of TF and PAI-1 were also measured. TF and PAI-1 mRNA were increased significantly in a concentration- and time-dependent manner. However, TFPI and TPA mRNA expression did not change. The inductions of TF and PAI-1 mRNAs were inhibited by a 5-HT1/5-HT2 receptor antagonist (methiothepin) and a selective 5-HT2A receptor antagonist (MCI-9042). These results indicate that 5-HT increases procoagulant activity and reduces fibrinolytic activities of endothelial cells through the 5-HT2A receptor. It was concluded that the modulation of procoagulant and hypofibrinolytic activities of endothelial cells by 5-HT synergistically promotes thrombus formation at the site of vessel injury with the platelet aggregation, VSMC contraction, and VSMC proliferation.

Animals↗

PubMed2001

NAD/NADH models with axial/central chiralities: superiority of the quinoline ring system.

Precursors of NAD model compounds 1c and 3a,b were successfully resolved into their atropisomers with respect to carbamoyl rotation. Atropisomers of quinoline derivatives are much more stable than pyridine derivatives as determined by cyclic voltammetry and X-ray crystallography. The 1,4-reduction of NAD model compound 4 was successfully achieved, affording novel NADH model compound 5. The rotational properties of the side chain of 5 were investigated by means of dynamic NMR. The rotational rate and syn/anti ratio, which indicate the orientation between carbonyl oxygen and hydrogen at the 4-position, are significantly affected by addition of magnesium ion. In the rotational transition state, the double-bond character of the C(carbonyl)-N(amide) bond is disrupted judging from the activation parameters. The oxidation of chiral 5 with p-benzoquinone in the presence of magnesium ion catalyst gave predominantly one enantiomer of 4. On the other hand, oxidation of 5 with p-chloranil (tetrachloro-p-benzoquinone) in the absence of magnesium ions affords the opposite enantiomer of 4 as the major product. The product enantiomer ratio is parallel to the syn/anti ratio in the starting material, indicating the importance of ground state conformation to stereochemistry of the reaction.

Crystallography, X-Ray↗

PubMed2001

Determination of a new thymidine phosphorylase inhibitor, TPI, in dog and rat plasma by reversed-phase ion-pair high-performance liquid chromatography.

A high-performance liquid chromatographic method for the determination of a new thymidine phosphorylase inhibitor, TPI, in dog and rat plasma is described. TPI was isolated from biological samples by solid-phase extraction on Bond Elut PRS columns. Chromatographic separation was achieved on a C18 column using a mobile phase consisting of acetonitrile-10 mM acetate buffer (pH 4.3) including hexanesulfonate, with UV detection at 276 nm. This method has been validated across the range of 50-50000 ng/ml using a 0.1-ml plasma volume. The mean recoveries from spiked plasma were 93% for dog and 94% for rat, respectively. The accuracy, precision and specificity of the method were demonstrated to be acceptable, and it was applied to the toxicokinetic study of TPI in rats.

Animals↗