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Biomedical subjects

T Furuta

Publications and source records attributed to T Furuta.

At least 55 records · Page 3Linked to original sources
PubMed2001

Effects of genotypic differences in CYP2C19 status on cure rates for Helicobacter pylori infection by dual therapy with rabeprazole plus amoxicillin.

Rabeprazole is a potent proton pump inhibitor and is mainly reduced to thioether rabeprazole by a non-enzymatic pathway and partially metabolized to demethylated rabeprazole by CYP2C19 in the liver. We intended to determine a cure rate for Helicobacter pylori infection by dual rabeprazole/amoxicillin therapy in relation to CYP2C19 genotype status prospectively. Ninety-seven patients with gastritis and H. pylori infection completed the dual therapy with 10 mg of rabeprazole bid and 500 mg of amoxicillin tid for 2 weeks. At 1 month after treatment, cure of H. pylori infection was assessed on the basis of histology, a rapid urease test, culture, polymerase chain reaction (PCR), and 13C-urea breath test. CYP2C19 genotype status was determined by a PCR-restriction fragment length polymorphism method. Of the 97 patients, 33 were homozygous extensive metabolizers (homEM), 48 were heterozygous extensive metabolizers (hetEM), and 16 were poor metabolizers (PM). Cure of H. pylori infection was achieved in 79 of the 97 patients (81.4%, 95%CI = 71.9-88.7). Significant differences in cure rates among the homEM, hetEM, and PM groups were observed; 60.6% (95%CI = 42.1-77.3), 91.7% (95%CI = 80.0-97.7), and 93.8% (95%CI = 69.8-99.8), respectively (P = 0.0007). Twelve patients without cure after initial treatment (10 homEMs and 2 hetEMs) were successfully retreated with rabeprazole 10 mg q.i.d. and amoxicillin 500 mg q.i.d. for 2 weeks. The cure rates for H. pylori infection by dual rabeprazole/amoxicillin therapy depended on the CYP2C19 genotype status. This dual therapy appears to be effective for hetEM and PM patients. However, high dose dual rabeprazole/amoxicillin therapy was effective even for homEM patients. Therefore, the genotyping test of CYP2C19 appears to be a clinically useful tool for the optimal dual treatment with rabeprazole plus amoxicillin.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Effects of Helicobacter pylori infection on gastric acid secretion and serum gastrin levels in Mongolian gerbils.

BACKGROUND AND AIMS: Body gastritis caused by Helicobacter pylori infection appears to inhibit gastric acid secretion. The aim of this study was to determine the effects of H pylori infection on gastric acid secretion and clarify its mechanisms with reference to interleukin 1beta (IL-1beta). METHODS: (1) Mongolian gerbils were inoculated orally with H pylori. Before, six, and 12 weeks after inoculation, serum gastrin levels, gastric acid output, and IL-1beta mRNA levels in the gastric mucosa were determined. Pathological changes were also determined according to the updated Sydney system. (2) Effects of recombinant human IL-1 receptor antagonist (rhIL-1ra) on gastric acid output and serum gastrin levels were also determined. RESULTS: (1) Scores for activity and inflammation of gastritis and serum gastrin levels were significantly increased, and gastric acid output was significantly decreased six and 12 weeks after inoculation with H pylori. IL-1beta mRNA levels in the gastric mucosa were also elevated six and 12 weeks after inoculation with H pylori. (2) Acid output and serum gastrin levels in the infected groups returned to control levels after rhIL-1ra injection. CONCLUSIONS: Gastric acid secretion is decreased and serum gastrin levels are increased in Mongolian gerbils infected with H pylori. This change in gastric acid secretion appears to be mediated by IL-1beta induced by H pylori infection.

Analysis of Variance↗
PubMed2001

Steroid pulse therapy combined with tonsillectomy in IgA nephropathy associated with diabetes mellitus.

Ten patients with biopsy-confirmed IgA nephropathy associated with diabetes mellitus underwent dietary weight control and three courses of intravenous pulses of methylprenisolone followed by prednisolone for 6-12 months and tonsillectomy. The average length of the follow-up period was 47.8 (range 30-96) months. As compared with pretreatment values, hematuria, proteinuria, body mass index, and hemoglobin A(1c) were significantly improved after treatment. There were no significant differences with regard to blood pressure and glycemic blood glucose control. There was no worsening of diabetic retinopathy and nephropathy. During steroid pulse therapy, the patients who were treated with insulin needed a higher dosage of insulin; after steroid pulse therapy, the dosage returned to baseline. Even patients with IgA nephropathy and diabetes mellitus could be treated with combined therapy and showed beneficial responses, it they succeeded in reducing body mass index.

Adult↗
PubMed2001

In vivo transduction of central neurons using recombinant Sindbis virus: Golgi-like labeling of dendrites and axons with membrane-targeted fluorescent proteins.

A new recombinant virus which labeled the infected neurons in a Golgi stain-like fashion was developed. The virus was based on a replication-defective Sindbis virus and was designed to express green fluorescent protein with a palmitoylation signal (palGFP). When the virus was injected into the ventrobasal thalamic nuclei, many neurons were visualized with the fluorescence of palGFP in the injection site. The labeling was enhanced by immunocytochemical staining with an antibody to green fluorescent protein to show the entire configuration of the dendrites. Thalamocortical axons of the infected neurons were also intensely immunostained in the somatosensory cortex. In contrast to palGFP, when DsRed with the same palmitoylation signal (palDsRed) was introduced into neurons with the Sindbis virus, palDsRed neither visualized the infected neurons in a Golgi stain-like manner nor stained projecting axons in the cerebral cortex. The palDsRed appeared to be aggregated or accumulated in some organelles in the infected neurons. Anterograde labeling with palGFP Sindbis virus was very intense, not only in thalamocortical neurons but also in callosal, striatonigral, and nigrostriatal neurons. Occasionally there were retrogradely labeled neurons that showed Golgi stain-like images. These results indicate that palGFP Sindbis virus can be used as an excellent anterograde tracer in the central nervous system.

Acylation↗
PubMed2001

A kinetic model for a biopanning process considering antigen desorption and effective antigen concentration on a solid phase.

A phage display library is a powerful tool for screening ligands such as antibodies and peptides that specifically recognize a target. In this study, we established a kinetic model describing the affinity selection process of phage display libraries and verified the model experimentally. Desorption of target molecules from a solid phase and orientation of the epitopes of adsorbed target molecules are taken into account in this model. The ratio of the effective antigen density to the total antigen density was estimated to be 0.0127(+/-)0.0018 when bovine pancreatic ribonuclease A (RNase A) adsorbed on polystyrene beads was recognized by an anti-RNase A single-chain Fv phage antibody. The model can faithfully describe the recovery of the phage antibody in a round of biopanning based on the effective concentration of RNase A on the beads, the desorption rate constant of RNase A from the beads, the dissociation constant and dissociation rate constant of the phage antibody from RNase A, and the time for blocking, equilibrium and washing in the biopanning process. A recommended biopanning protocol based on the model is also described.

Journal Article↗
PubMed2001

Characterization of the cellulose-binding ability of Geotrichum sp. M111 cells and its application to dehydration of the distilled waste of sweet potato shouchu.

The cellulose-binding ability of Geotrichum sp. M111 cells was investigated by the micro-tube method which gives an indication of the binding ability of M111 cells. The optimum pH value and temperature were 3-7 and below 50 degrees C, respectively, from measurement of the aggregation height for a mixture of cellulose powder and M111 cells. The binding constant of 0.3% for M111 cells to cellulose powder was obtained in a 20 mm citrate buffer of pH 5.0 at 30 degrees C. Aggregation was inhibited by such surfactants as sodium dodecylsulfate. The binding ability of M111 cells to cellulose fiber disappeared after a treatment with Driselase or Pronase E. This suggests that the binding ability might be related to the cell surface proteins. The dehydration rate of the distilled waste of sweet potato shouchu was accelerated by the addition of M111 cells. The analysis of dehydration by a linear viscoelastic model suggests that the acceleration effect might have been due to the space increase between cellulose fibers with the cell addition.

Cellulose↗
PubMed2001

Pneumocystis carinii pneumonia in a Cavalier King Charles Spaniel.

Pneumocystis carinii pneumonia was diagnosed by postmortem examination of a one-year-old Cavalier King Charles Spaniel with four-week history of dyspnea. Cytologic and histologic examination of lung tissues revealed numerous P. carinii trophozoites and cysts, and P. carinii specific DNA was detected by polymerase chain reaction. The dog showed hypogammagloblinemia and extremely low levels of serum IgG. It was considered that P. carinii pneumonia in this case was associated with an immunodeficient condition which has already been reported in Miniature Dachshunds.

Animals↗
PubMed2001

Horizontal transmission of Toxoplasma gondii in squirrel monkeys (Saimiri sciureus).

The possibility of horizontal transmission of T. gondii was examined in squirrel monkeys. After three monkeys were inoculated perorally with 1.1-2.1 x 10(3) cysts of the T. gondii ME49, the animals were divided into two cages and maintained with one normal monkey for each cage as a cagemate. Two out of the three T. gondii-inoculated monkeys died, and the remaining one monkey was sacrificed in a moribund state one week after infection because of acute toxoplasmosis. Many T. gondii tachyzoites were recovered from broncho-alveolar lavages and were also found histopathologically in the lung, liver, spleen, kidney and lymph nodes and impression smears of tissues from the three T. gondii-inoculated monkeys by Giemsa staining. Anti-T. gondii antibody was examined by immunoblot assay in these animals, and the antibody to T. gondii major surface membrane protein (p30) could be detected after the start of experiment. Furthermore, a specific band of T. gondii NTPase gene was observed by PCR in the liver and lung of infected and cagemate monkeys, and the sequence of the second PCR products obtained from the cagemates, which were clinically normal but gave a positive result in immunoblotting assay, was exactly the same as the sequence of the NTPase gene of T. gondii ME49. These findings suggested that transmission of T. gondii from the infected monkeys to cagemates occurred easily, and since many T. gondii tachyzoites were recovered from the bronchoalveolar lavages of the three T. gondii-inoculated monkeys, we suggest that aerosol infection plays an important role for the enzootic toxoplasmosis in colonies of squirrel monkeys.

Aerosols↗
PubMed2001

Case report. Cryptococcal cellulitis showing necrotizing vasculitis.

A 65-year-old woman with refractory anaemia who had been treated with systemic corticosteroids for several months developed cryptococcal cellulitis of the right cubital fossa. She was treated empirically for a presumed bacterial cellulitis with little response. Histological examination of debrided tissue revealed Cryptococcus as the causative organism. The tissue reaction involved suppurative inflammation with abscess formation in the dermis and subcutaneous adipose tissue. Necrotizing vasculitis, which has rarely been described in cryptococcosis, was seen in this case. Although the cellulitis was cured by local treatment in this patient, most previous reports recommended systemic antifungal therapy to treat cryptococcal cellulitis.

Aged↗
PubMed2000

Third group of neostriatofugal neurons: neurokinin B-producing neurons that send axons predominantly to the substantia innominata.

Neostriatal neurons that produce neurokinin B were investigated immunocytochemically in the rat brain with an antibody against the C-terminal portion of the precursor prepropeptide of neurokinin B, preprotachykinin B (PPTB). PPTB-immunoreactive neurons were scattered throughout the neostriatum and constituted 5.1% of neostriatal neurons. They were immunopositive for projection neuron markers, such as precursor peptides of substance P, enkephalins, and dynorphins, but negative for intrinsic neuron markers, suggesting that PPTB was expressed in neostriatal projection neurons. However, PPTB-immunoreactive neurons were immunonegative for dopamine- and cyclic AMP-regulated phosphoprotein, which is known to be produced by striatopallidal and striatonigral neurons. Furthermore, almost no PPTB-immunoreactive axon terminals were observed in the substantia nigra or globus pallidus. The authors then made large kainic acid lesions in the neostriatum to reveal the target areas of PPTB-producing neurons and observed a decrease in PPTB-immunoreactive fibers in the sublenticular portion of the substantia innominata and, to much lesser extent, in the bed nucleus of the stria terminalis and central nucleus of the amygdala. After injection of wheat germ agglutinin into the substantia innominata, PPTB immunoreactivity was detected in many retrogradely labeled neostriatal neurons. In contrast, no PPTB immunoreactivity was observed in striatonigral or striatopallidal neurons after injection of retrograde tracers into the substantia nigra or globus pallidus. Thus, neurokinin B-producing neostriatal neurons were considered to send projection fibers predominantly to the substantia innominata. Furthermore, PPTB-immunoreactive axonal swellings were closely apposed to neurokinin B receptor-immunoreactive dendrites in the substantia innominata. Overall, the present results indicate that the rat brain possesses a chemically and hodologically unique neostriatofugal pathway in addition to the direct and indirect pathways.

Animals↗
PubMed2000

Simultaneous determination of 6beta- and 6alpha-hydroxycortisols and 6beta-hydroxycortisone in human urine by stable isotope dilution mass spectrometry.

A capillary gas chromatographic-mass spectrometric method for the simultaneous determination of 6beta-hydroxycortisol (6beta-OHF, 6beta,11beta,17alpha,21-tetrahydroxypregn-4-ene- 3,20-dione), 6alpha-hydroxycortisol (6alpha-OHF, 6alpha,11beta,17alpha,21-tetrahydroxypregn-4-ene -3,20-dione) and 6beta-hydroxycortisone (6beta-OHE, 6beta,17alpha,21-trihydroxypregn-4-ene-3,11,20-trione) in human urine is described. Deuterium-labelled compounds, 6beta-[1,1,19,19,19-2H5]OHF (6beta-OHF-d5), 6alpha-[1,1,19,19,19-2H5]OHF (6alpha-OHF-d5) and 6beta-[1,1,19,19,19-2H5]OHE (6beta-OHE-d5) were used as internal standards. Quantitation was carried out by selected-ion monitoring of the characteristic fragment ions ([M-31]+) of the methoxime-trimethylsilyl (MO-TMS) derivatives of 6beta-OHF, 6alpha-OHF and 6beta-OHE. The sensitivity, specificity, precision and accuracy of the method were demonstrated to be satisfactory for measuring 6beta-OHF, 6alpha-OHF and 6beta-OHE in human urine.

Calibration↗
PubMed2000

Simultaneous determination of endogenous and 13C-labelled cortisols and cortisones in human plasma by stable isotope dilution mass spectrometry.

This study describes a capillary GC-MS method for the simultaneous determination of endogenous cortisol and cortisone and their 13C-labelled analogues, [1,2,4,19-13C4]cortisol (cortisol-13C4) and [1,2,4,19-13C4]cortisone (cortisone-13C4), in human plasma. [1,2,4,19-13C4,1,1,19,19,19-2H5]Cortisol (cortisol-13C4,2H5) and [1,2,4,19-13C4,1,1,19,19,19-2H5]cortisone (cortisone-13C4,2H5) were used as analytical internal standards. A double derivatization (bismethylenedioxy-pentafluoropropionate, BMD-PFP) with good GC behavior was employed for the GC-MS analysis of cortisol and cortisone. Quantitation was carried out by selected-ion monitoring of the molecular ions ([M]+*) of the BMD-PFP derivatives of cortisol and cortisone. The sensitivity limit of the present GC-MS-SIM method was found to be 150 pg per injection for cortisol (s/n=5.0) and 50 pg for cortisone (s/n=8.1). The within-day reproducibility in which the amounts of unlabelled and labelled cortisols and cortisones determined were in good agreement with the actual amounts added, the relative errors being less than 3.07%. The inter-assay coefficients of variation (C.V.) were less than 1.80% for unlabelled and labelled cortisols and cortisones.

Carbon Isotopes↗
PubMed2000

First synthesis of tetrapyrrolylporphyrin

[reaction: see text] N-alkyl-substituted meso-tetrapyrrolylporphyrin (TPyrP) and its derivatives were synthesized for the first time via an acid-catalyzed condensation between N-alkyl-2,4-diformylpyrrole and unsubstituted pyrrole and a subsequent deformylation reaction. X-ray structural analysis of formyl-substituted TPyrP shows the tilting of meso pyrrole rings ca. 60 degrees to the porphyrin plane. Formyl groups of meso pyrrole rings were removed by treatment with trifluoroacetic acid (TFA) in pyrrole.

Journal Article↗
PubMed2000

Experimental gene therapy for brain tumors using adenovirus-mediated transfer of cytosine deaminase gene and uracil phosphoribosyltransferase gene with 5-fluorocytosine.

Transduction of the cytosine deaminase (CD) gene into tumor cells followed by administration of 5-fluorocytosine (5-FC), called 5-FC/CD gene therapy, was created as suicide gene therapy for various cancers. The uracil phosphoribosyltransferase (UPRT) gene, which is absent from mammalian cells, directly converts 5-fluorouracil (5-FU) to 5-fluorouridine 5'-monophosphate. We evaluated whether the coexpression of CD and UPRT genes could generate a synergistic antitumor effect on experimental brain tumors. In vitro study showed that 9L cells, transduced with the UPRT gene by an adenovirus, were 16 times more sensitive to 5-FU, and CD + UPRT-transduced cells were 6,000 times more sensitive to 5-FC than parent cells, indicating that the acquisition of CD and UPRT further increased the 5-FC sensitivity of 9L cells compared with cells transduced with CD alone. In a rat brain tumor model, decreased amounts of CD and UPRT vectors were inoculated into the tumors to detect any additional effect of UPRT. CD and UPRT coexpression followed by 5-FC administration showed an antitumor effect as detected by sequential magnetic resonance imaging. This therapy significantly prolonged animal survival. These results suggest that 5-FC/CD + UPRT gene therapy can enhance the antitumor effect of 5-FC/CD gene therapy. Consequently, this approach might be a more feasible modality for the treatment of malignant brain tumors.

Adenoviridae↗
PubMed2000

Proton magnetic resonance spectroscopy reflects cellular proliferative activity in astrocytomas.

We examined whether proton magnetic resonance spectroscopy (MRS) could provide accurate information on histological grade and cell proliferation in astrocytomas. We studied 23 patients with astrocytomas: five grade II, 10 grade III and eight with grade IV (glioblastoma multiforme). We performed proton MRS and determined the Ki-67 labeling index (LI), a tumour proliferation marker, in the same areas of the astrocytomas, and examined the statistical relationship between proton MRS and Ki-67 LI. The N-acetylaspartate (NAA)/creatine-phosphocreatine (Cr) and NAA/choline (Cho)-containing compound ratios were always significantly lower and the Cho/Cr ratios significantly higher than those for normal brain. The Cho/Cr ratio correlated positively and the NAA/Cho ratio inversely with Ki-67 LI. These findings suggest that the Cho signal in proton MRS reflects cellular proliferation. In Kaplan-Meier survival analysis, there was no significant difference between high (> 2.0, 14 cases) and low (< 2.0, 9 cases) Cho/cr ratio groups.

Adolescent↗