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Biomedical subjects

T Furuta

Publications and source records attributed to T Furuta.

At least 73 records · Page 4Linked to original sources
PubMed2000

Hyperpolarization is not responsible for the acetylcholine-induced negative chronotropic action in the presence of isoproterenol.

It has been reported that acetylcholine hyperpolarizes the maximum diastolic potential of canine Purkinje fibers through a pathway involving a G protein and induces a decrease in their automaticity. It is unclear, however, whether the negative chronotropic action of acetylcholine in the presence of beta-adrenergic stimulation is due to the hyperpolarization of the maximum diastolic potential or a decrease in the slope of phase 4 depolarization. We used standard microelectrode techniques to study the negative chronotropic mechanism of acetylcholine in the presence of isoproterenol in adult canine Purkinje fibers. Fibers were incubated for 24 hours in Tyrode's solution alone (n = 10) or plus pertussis toxin (n = 10), and then superfused with acetylcholine (10(-9) to 10(-4) M) in the presence of isoproterenol (10(-7) M). Acetylcholine in the presence of isoproterenol significantly decreased automaticity without hyperpolarization of the maximum diastolic potential, and decreased the slope of phase 4 depolarization. The effects of acetylcholine on automaticity and the slope of phase 4 depolarization were attenuated by pertussis toxin. The present findings indicate that the negative chronotropic action of acetylcholine in the presence of isoproterenol is due to the decrease in the slope of phase 4 depolarization through a pathway involving a pertussis toxin-sensitive G protein and that it is not the result of hyperpolarization of the maximum diastolic potential.

Acetylcholine↗
PubMed2000

The use of deuterium-labeled cortisol for in vivo evaluation of renal 11beta-HSD activity in man: urinary excretion of cortisol, cortisone and their A-ring reduced metabolites.

This study describes a new approach using stable isotope methodology in evaluating 11beta-HSD activities in vivo based on urinary excretion of cortisol, cortisone, and their A-ring reduced metabolites. The method involved the measurement of deuterium-labeled cortisol and its deuterium-labeled metabolites by GC/MS simultaneously with endogenous cortisol, cortisone, and their A-ring reduced metabolites after oral administration of deuterium-labeled cortisol to normal human subjects. This stable isotope approach offered unique advantages in assessing the appropriateness of measuring unconjugated and total (unconjugated + conjugated) cortisol, cortisone, and their A-ring reduced metabolites in urine as indices of renal 11beta-HSD2 activity in man. Our results strongly support that the measurement of urinary unconjugated cortisol and cortisone is a significant advance in assessing 11beta-HSD2 activity.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2000

Synthesis of multi-labeled cortisols and cortisones with (2)H and (13)C for study of cortisol metabolism in humans.

A method is described for the preparation of multi-labeled cortisol and cortisone with (13)C and (2)H via the indan synthon method, starting from chiral 11-oxoindanylpropionic acid. [1, 3-(13)C(2)]Acetone was used for the syntheses of [1,2,4, 19-(13)C(4)]cortisol (cortisol-(13)C(4)) and [1,2,4, 19-(13)C(4)]cortisone (cortisone-(13)C(4)), and [1,3-(13)C(2),1,1,1, 3,3,3-(2)H(6)]acetone was for [1,2,4,19-(13)C(4),1,1,19,19, 19-(2)H(5)]cortisol (cortisol-(13)C(4),(2)H(5)) and [1,2,4, 19-(13)C(4),1,1,19,19,19-(2)H(5)]cortisone (cortisone-(13)C(4), (2)H(5)). The chemical shifts for the (13)C and (1)H NMR spectra of cortisol and cortisone were fully assigned.

Carbon Isotopes↗
PubMed2000

Neurons in Golgi-stain-like images revealed by GFP-adenovirus infection in vivo.

Neurons in the adult brain have a very complex morphology with many processes, including tremendously long axons. Since dendrites and axons play key roles in the input and output of neural information, respectively, the visualization of complete images of these processes is necessary to reveal the mechanism of neural information processing. Here we made a recombinant adenovirus vector which encodes green fluorescent protein (GFP) tagged with a palmitoylation site, a membrane-targeting signal, produced specific antibodies to GFP, and used them as probes for staining the nervous system. In the neocortex, after injection of the recombinant virus and immunoperoxidase staining with the antibodies, many different types of cells were labeled in a Golgi stain-like fashion. Although the number of labeled cells varied depending on the amount of virus injected, the recombinant virus was considered to be infectious to cortical neurons of all cell types without selectivity. In contrast, the viral infection in the cerebellar cortex and superior cervical ganglion showed some selectivity toward the cell type. It is expected that this recombinant virus will be a useful tool for the morphological analysis of neuronal connections, especially the analysis of microcircuitry in the cerebral cortex.

Adenoviridae↗
PubMed2000

Mass spectrometric identification and high-performance liquid chromatographic determination of a flavonoid glycoside naringin in human urine.

The aim of this study was to evaluate the absorption of a citrus flavonoid, naringin, as its glycosylated form. Six healthy volunteers (three males and three females) were studied. After a single oral administeration of 500 mg of naringin, intact naringin was isolated from 2-4 h urine. Isolated naringin was identified by the LC/electrospray ionization mass spectrometry (ESI-MS), MS/MS, and MS/MS/MS techniques. The cumulative urinary excretion of naringin and its metabolites (naringenin and naringenin glucuronides) was determined by HPLC for 0-24 h. Approximately 0.02% of the administered dose was recovered in urine as unchanged naringin, whereas urinary recoveries of naringenin and naringenin glucuronides were approximately 0.4 and 3.6% of the administered dose, respectively. It was concluded that trace amounts of orally administered naringin can be absorbed as the glycoside. However, it is not clear whether the glycoside is cleaved before or after absorption to generate naringenin.

Antioxidants↗
PubMed2000

Intrathecal chemotherapy with MX2 for treating glioma dissemination in vivo.

We examined whether the intrathecal MX2 chemotherapy for treating dissemination of malignant glioma would be a feasible therapy. In the toxicity study, physiological and histological neurotoxicity was not observed in the rats treated with less than 100 microg/kg of MX2 administered intracisternally. But physiological side effects were observed in the treatment group of more than 200 microg/kg and histological brain toxicity was in the treatment group of more than 1000 microg/kg. Dissemination models were induced in rats by intracisternal inoculation of C6 glioma cells. The median survival times of the rats treated with 100 microg/kg of intrathecal MX2 on day 1, 3, or 7 after tumor inoculation were prolonged by 52.4% (p = 0.0006), 31.5% (p = 0.0007), and 7.1% (p = 0.0180), respectively, compared to that of untreated control animals. Intrathecal MX2 treatment also cured 33.6% of rats in the treatment group. These findings suggested that there was a possibility that intrathecal MX2 would be a safe and effective method for treating dissemination of malignant glioma.

Animals↗
PubMed2000

In vivo efficacy and toxicity of 5-fluorocytosine/cytosine deaminase gene therapy for malignant gliomas mediated by adenovirus.

We evaluated the therapeutic efficacy and neurotoxicity of adenovirus-mediated transduction of the cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) for experimental malignant brain tumors. The 5-FC sensitivity in 9 L cells infected by an adenovirus vector expressing CD (AdexCACD) was increased 1700-fold compared with control cells. Rats bearing 9 L brain tumors were treated with an intratumoral injection of AdexCACD followed by intraperitoneal administration of 5-FC. The rats demonstrated remarkable inhibition of tumor growth by magnetic resonance imaging, and 7 of 10 rats survived for >90 days. To evaluate the potential side-effects of the 5-FC/CD gene therapy, rats were treated with an intracerebral injection of AdexCACD into the right basal ganglia and with 5-FC. The magnetic resonance imaging showed a highly enhanced area on the gadollinium-enhanced T1-weighted image at 18 days postinjection. Pathologically, this corresponded to an area of necrosis with surrounding apoptotic cells. In addition, there was demyelination and gliosis with enlargement of the lateral ventricles. These results suggest that the 5-FC/CD gene therapy may provide an anticancer effect for malignant brain tumors in humans, but also show that there are neurotoxic effects on normal brain tissue.

Adenoviridae↗
PubMed2000

Cure of refractory duodenal ulcer and infection caused by Helicobacter pylori by high doses of omeprazole and amoxicillin in a homozygous CYP2C19 extensive metabolizer patient.

A 53-year old female patient with duodenal ulcer and Helicobacter pylori infection was treated three times with a proton pump inhibitor-based triple therapy, such as lansoprazole-clarithromycin-amoxicillin (INN, amoxicilline) and lansoprazole-minocycline-cefaclor. However, the H pylori infection was not cured. A culture test revealed that her infection was a clarithromycin-resistant but amoxicillin-sensitive strain of H pylori. Moreover, a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis revealed that she was a homozygous extensive metabolizer of cytochrome P450 (CYP) 2C19 (wt/wt). The usual dose of the proton pump inhibitor was therefore assumed to be insufficient for her and then she was treated with a high dose of omeprazole (120 mg/day) and amoxicillin (2,250 mg/day) for 2 weeks. The H pylori infection and the ulcer lesion were then cured. One of the factors associated with success or failure of cure of H pylori infection by the proton pump inhibitor-based triple therapy appeared to be CYP2C19 genotype status. Dual treatment with a sufficient dose of a proton pump inhibitor plus amoxicillin could cure H pylori infection even after the failure to cure H pylori infection by a usual proton pump inhibitor-based triple therapy in patients with the wt/wt homozygous extensive metabolizer genotype of CYP2C19.

Amoxicillin↗
PubMed2000

EMB-30: an APC4 homologue required for metaphase-to-anaphase transitions during meiosis and mitosis in Caenorhabditis elegans.

Here we show that emb-30 is required for metaphase-to-anaphase transitions during meiosis and mitosis in Caenorhabditis elegans. Germline-specific emb-30 mutant alleles block the meiotic divisions. Mutant oocytes, fertilized by wild-type sperm, set up a meiotic spindle but do not progress to anaphase I. As a result, polar bodies are not produced, pronuclei fail to form, and cytokinesis does not occur. Severe-reduction-of-function emb-30 alleles (class I alleles) result in zygotic sterility and lead to germline and somatic defects that are consistent with an essential role in promoting the metaphase-to-anaphase transition during mitosis. Analysis of the vulval cell lineages in these emb-30(class I) mutant animals suggests that mitosis is lengthened and eventually arrested when maternally contributed emb-30 becomes limiting. By further reducing maternal emb-30 function contributed to class I mutant animals, we show that emb-30 is required for the metaphase-to-anaphase transition in many, if not all, cells. Metaphase arrest in emb-30 mutants is not due to activation of the spindle assembly checkpoint but rather reflects an essential emb-30 requirement for M-phase progression. A reduction in emb-30 activity can suppress the lethality and sterility caused by a null mutation in mdf-1, a component of the spindle assembly checkpoint machinery. This result suggests that delaying anaphase onset can bypass the spindle checkpoint requirement for normal development. Positional cloning established that emb-30 encodes the likely C. elegans orthologue of APC4/Lid1, a component of the anaphase-promoting complex/cyclosome, required for the metaphase-to-anaphase transition. Thus, the anaphase-promoting complex/cyclosome is likely to be required for all metaphase-to-anaphase transitions in a multicellular organism.

Alleles↗
PubMed2000

Spinal atypical teratoid/rhabdoid tumor in an infant.

Atypical teratoid/rhabdoid tumor of the central nervous system in infancy and childhood was established as an entity based on histological, immunohistochemical, and cytogenetic studies. We report the case of a 7-month-old girl who presented with progressive paraplegia and hypesthesia of her legs. Imaging studies revealed a spinal cord mass occupying the entire spinal canal below the T(7) level. Through a T(12)-L(3) laminectomy, the intramedullary tumor was partially debulked. Histologically, the tumor specimen had rhabdoid cells, and immunostaining showed vimentin and cytokeratin positivity. No abnormality of chromosome 22q was detected with the fluorescence in situ hybridization method.

Biomarkers, Tumor↗
PubMed2000

Crystal transformation from anhydrous alpha-maltose to hydrous beta-maltose and from anhydrous trehalose to hydrous trehalose.

Anhydrous sugars such as maltose and trehalose are useful for making dry powder of foods and liquids. The crystal-transformation rate of maltose and trehalose were investigated under humid conditions and by kneading. The enthalpy for solubilization was 7.0 kJ/mol for the anhydrous maltose. The crystal-transformation rate of anhydrous alpha-maltose to hydrous beta-maltose depended on the temperature at 75% humidity. However, that of anhydrous trehalose did not depend on the temperature, and transformation was very rapid. An anomeric change to maltose and no such change to trehalose might have caused this. The activation energy of crystal transformation was 79 kJ/mol for maltose and zero for trehalose. The rate of crystal transformation of anhydrous maltose while kneading depended on the purity of the anhydrous alpha-maltose and the amount of water present. This crystal transformation rate fitted the Avrami equation.

Crystallization↗
PubMed2000

Refolding of denatured/reduced lysozyme at high concentration with diafiltration.

Refolding of reduced and denatured protein in vitro has been an important issue for both basic research and applied biotechnology. Refolding at low protein concentration requires large volumes of refolding buffer. Among various refolding methods, diafiltration is very useful to control the denaturant and red/ox reagents in a refolding solution. We constructed a refolding procedure of high lysozyme concentration (0.5-10 mg/ml) based on the linear reduction of the urea concentration during diafiltration under oxygen pressure. When the urea concentration in the refolding vessel was decreased from 4 M with a rate of 0.167 M/h, the refolding yields were 85% and 63% at protein concentrations, 5 mg/ml and 10 mg/ml, respectively, after 11 h. This method gave a high productivity of 40.1,microM/h of the refolding lysozyme. The change in refolding yields during the diafiltration could be simulated using the model of Hevehan and Clark.

Animals↗
PubMed2000

Cyclodextrin encapsulation to prevent the loss of l-menthol and its retention during drying.

The taste and flavor of spray-dried powdered products are the most important quality factors. In the present study, molecular encapsulation in cyclodextrin was applied to prevent the loss of a hydrophobic flavor compound (l-menthol) during the drying of a droplet. beta-Cyclodextrin appeared to be a better encapsulant for menthol than alpha- and gamma-cyclodextrin. The retention of menthol increased with increasing concentration of both cyclodextrin and maltodextrin. A simple mathematical model is proposed for estimating the flavor retention. The theoretical results by this model estimated well the final retention of menthol encapsulated in a blend of beta-cyclodextrin and maltodextrin.

Cyclodextrins↗
PubMed2000

Ganglioglioma in a patient with Turcot syndrome. Case report.

A 33-year-old woman with Turcot syndrome harbored a brain tumor and colon cancer and had a familial history of this syndrome. On histological examination, the brain tumor was found to have large and diffusely scattered ganglion cells within a diffuse background of astrocytic cells in a fibrillary matrix. The tumor was diagnosed as a ganglioglioma. No germline mutation in the adenomatous polyposis coli gene was detected using a protein truncation assay. These findings indicate that this patient had brain tumor-polyposis syndrome Type 1 of Turcot syndrome. This is the first report of a ganglioglioma related to Turcot syndrome.

Adenomatous Polyposis Coli↗
PubMed2000

FR901469, a novel antifungal antibiotic from an unidentified fungus No.11243. II. In vitro and in vivo activities.

FR901469 is a water-soluble macrocyclic lipopeptidolactone (C71H116N14O23) that has inhibitory activity against 1,3-beta-glucan synthase and exhibits in vitro and in vivo antifungal activity against both Candida albicans and Aspergillus fumigatus. The MICs of FR901469 against Candida albicans FP633 and Aspergillus fumigatus FP1305 in a micro-broth dilution test were 0.63 and 0.16 microg/ml, respectively. FR901469 showed excellent efficacy by subcutaneous injection against both Candida albicans and Aspergillus fumigatus in a murine systemic infection mode, with ED50s of 0.32 and 0.2 mg/kg, respectively. This compound also showed potent anti-Pneumocystis activity in the nude mice model with experimental Pneumocystis pneumonia. The hemolytic activity of FR901469 towards mouse red blood cells, is about 30-fold weaker than that of amphotericin B.

Animals↗
PubMed2000

[Relationship between the chemical structure of O-methyl erythromycin derivatives and their affinity to the lung].

Clarithromycin (CAM) was synthesized by selective methylation of the C-6-hydroxy group of erythromycin (EM), which had a high affinity to the lung. In the present study, the relationship between the chemical structure of derivatives of O-methyl group for the hydroxy group at 6, 11, 12 and 4"-position of the EM and their affinity to the lung was investigated. When each O-methyl EM derivatives was injected into the external jugular vein in rats, the lung levels were in decreasing order, 6,11,12,4"-OCH3 > 6,12-OCH3 > 6,11,4"-OCH3 > 6,4"-OCH3 > 6,11-OCH3 > 6-OCH3 > 11-OCH3 > EM. There was not a correlation between the lung affinity and dissociation constant (pKa). It was found that substitution of a O-methyl group for the hydroxy group at each position afforded both the affinity to the lung and the lipophilicity. However, the levels of the increase were inconsistent for each substitution position. In the case of 6 and 12-position afforded higher affinity than that for 11 and 4"-position. A study of the effect of EM derivatives on the [14C]EM and [14C]CAM uptake process into the isolated lung cells was carried. The uptake of [14C]EM was not influenced by EM, CAM and 6,11,12,4"-OCH3. On the other hand, the uptake of [14C]CAM was significantly inhibited in the presence of derivatives which had a O-methyl substitution at position 6, but was not influenced by an O-acethyl substitution. These findings suggest that CAM is transported via carrier-mediated system in the lung cells, which has a selective recognition the O-methyl group at position 6. In addition, the uptake of [14C]CAM was further inhibited by the derivatives with O-methyl group at position 12.

Animals↗
PubMed2000

[A Warthin's tumor showing extensive necrosis].

Warthin's tumors are one of the most easily recognizable tumors using light microscopy. However, histopathological diagnosis is difficult in a few cases when characteristic cystic cavities with papillary walling and underlying lymphoid stroma are obscured by reactive changes. We describe a case of an extirpated Warthin's tumor of the right parotid gland which demonstrated extensive necrosis, squamous metaplasia and xanthomatous inflammation. No characteristic structure for this tumor was noticed in a section of an initially sampled specimen. As a result, a destroyed fistula was suspected. An additional sampling was performed to confirm the diagnosis and the sampled specimen fortunately demonstrated the diagnostic structure of a Warthin's tumor excluding malignancy. An awareness of the morphological variation seen in this tumor should lead to additional sampling of specimens, thereby preventing erroneous interpretation.

Adenolymphoma↗