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Biomedical subjects

Tatsuya Kikuchi

Publications and source records attributed to Tatsuya Kikuchi.

12 recordsLinked to original sources

[Status of measures against angiography room infection as determined by questionnaire].

Although the cleanliness of the angiography room and that of the operating room have long been equally attended to, the concept of Standard Precautions (including the basic measures and procedures to prevent infection) of the Centers for Disease Control and Prevention (CDC), 1996, as well as the introduction of transmission-based precautions, have been changing to preventive measures that are based on concrete measures. Therefore, a questionnaire was introduced in order to determine the actual status of countermeasures against infection used in the angiography room. The questionnaire was sent to 530 institutions, and 286 responded, a response rate of 54.0%. Its results significantly revealed the following: 1) unexpectedly low recognition of the need and importance for the CDC preventive measures against infection, 2) a considerable number of institutions continuing to perform the conventional preventive measures, 3) problems with education systems on preventive measures, and 4) handwashing, the most important measure against infection, failing to be adequately carried out noticeably among radiological technologists.

Angiography↗

Efficacy and safety of endoscopic balloon dilation for Crohn's strictures.

PURPOSE: This study was designed to investigate retrospectively the efficacy and safety of endoscopic balloon dilation for intestinal strictures in Crohn's disease. METHODS: Sixteen patients with 20 strictures were treated. The stricture sites were as follows: at the ileocolonic (n = 6) or ileoileal (n = 1) anastomosis, in the colon (n = 10), ileum (n = 2), and at the ileocecal valve (n = 1). The dilations were performed with through-the-scope balloons, with diameters of 15 to 20 mm on inflation and lengths of 30 to 80 mm. RESULTS: In 15 of 16 patients, the strictures were successfully dilated and the symptoms caused by the strictures disappeared after the first session. The patients were followed for a median of 38.5 months. Repeat symptomatic stricture formation occurred after a mean of 19.7 months in seven patients. Four patients needed second-round dilation and three patients were treated surgically. Complications occurred in four patients who had primary strictures: bleeding in one, high fever in one, and colorectal perforation in two. One of the patients complicated with colorectal perforation was treated surgically, and the other was treated conservatively. The cumulative nonsurgical rates for the dilation strictures were 93 percent at 12 months and 65 percent at 36 months, respectively. Three patients were treated surgically because of strictures or fistulas that were not related to the procedure of dilation. As a whole, the cumulative nonsurgical rates were 81 percent at 12 months and 46 percent at 36 months. Nine patients (56.3 percent) were able to avoid surgery. CONCLUSIONS: Using endoscopic balloon dilation, it may be possible to avoid or postpone surgery. Primary strictures seem to have increased risk of perforation.

Adult↗

An approach for measuring in vivo cerebral redox states using the oxidative conversion of dihydropyridine to pyridinium ion and the metabolic trapping principle.

This study was undertaken to develop radiopharmaceuticals for measuring in vivo cerebral redox states. Based on the oxidative conversion of dihydropyridine to pyridinium ion and the metabolic trapping principle, five N-[(14)C]methyl-3 or 3,5-substituted 1,4-dihydropyridines with different oxidation rates were designed, synthesized, and evaluated as a prototype of radiotracers for measuring in vivo cerebral redox states. When these tracers were injected into mice, they crossed the blood-brain barrier (BBB) and became trapped in the brain depending on their oxidation rates, while the corresponding oxidized forms hardly crossed the BBB. Furthermore, a significant increase in the radioactivity trapped in the brain was observed following injection of N-[(14)C]methyl-3-acetyl-1,4-dihydropyridine to mice pretreated with diethylmaleate that depletes glutathione in the brain. These findings suggested that an approach based on the oxidative conversion of dihydropyridine to the pyridinium ion and the metabolic trapping principle would be useful for measuring in vivo cerebral redox states.

Animals↗

N-[18F] fluoroethylpiperidin-4ylmethyl acetate, a novel lipophilic acetylcholine analogue for PET measurement of brain acetylcholinesterase activity.

The reduction of acetylcholinesterase (AChE) activity in the brain has been measured in dementia disorders such as Alzheimer's disease and dementia with Lewy bodies using (11)C-labeled acetylcholine analogues, N-[(11)C]methylpiperidin-4-yl acetate and propionate, and positron emission tomography (PET). Our aim was to develop an (18)F-labeled acetylcholine analogue useful for brain AChE mapping with PET, since (18)F, with a longer half-life, has advantages over (11)C. In a preliminary study, a series of N-[(14)C]ethylpiperidin-3-yl or -4-ylmethanol esters (acetyl and propionyl esters) were newly designed and evaluated in vitro regarding the reactivity with and specificity to AChE using purified human enzymes, leading to a novel (18)F-labeled acetylcholine analogue, N-[(18)F]fluoroethylpiperidin-4-ylmethyl acetate. In rat experiments, the (18)F-labeled candidate showed desirable properties for PET AChE measurement: high brain uptake of the authentic ester, high AChE specificity, a moderate hydrolysis rate, and low membrane permeability (metabolic trapping) of the metabolite.

Acetates↗

Estimation of plasma IC50 of donepezil hydrochloride for brain acetylcholinesterase inhibition in monkey using N-[11C]methylpiperidin-4-yl acetate ([11C]MP4A) and PET.

Donepezil hydrochloride is a potent and selective inhibitor for brain acetylcholinesterase (AChE) and is currently used worldwide for the treatment of Alzheimer's disease. Until now, there is no in vivo study on the relation between the plasma concentration and the brain AChE inhibition. The purpose of this study was to estimate in vivo plasma IC(50) of donepezil in living monkeys by measuring plasma donepezil concentration (LC/MS/MS) and brain AChE activity with positron emission tomography (PET) and N-[(11)C]methylpiperidin-4-yl acetate, which is an acetylcholine analog recently developed by us for quantifying in vivo brain AChE activity. PET scans with donepezil at two doses, 100 microg/kg (donepezil-1; N=5) or 250 microg/kg (donepezil-2; N=5), were performed using the same monkeys at 4-week intervals. Before each PET scan, baseline PET scans (N=10 in total) were performed without donepezil. The plasma donepezil concentrations 14 min after intravenous injection were proportional to the doses, 17.2+/-2.9 ng/ml (donepezil-1) and 44.0+/-5.0 ng/ml (donepezil-2), and the mean AChE inhibitions in four neocortical regions as evaluated by PET were also dose-dependent, 27% (donepezil-1) and 53% (donepezil-2). In IC(50) estimation, measured plasma donepezil concentrations were corrected for the change during PET scan. The IC(50) values (estimate+/-SE) were 42+/-9.0 (ng/ml; donepezil-1), 34+/-3.2 (donepezil-2), and 37+/-4.1 (combined data). The present method may be useful for in vivo evaluation of other AChE inhibitors and novel drugs.

Acetylcholinesterase↗

Curli fibers are required for development of biofilm architecture in Escherichia coli K-12 and enhance bacterial adherence to human uroepithelial cells.

Sessile bacteria show phenotypical, biochemical, and morphological differences from their planktonic counterparts. Curli, extracellular structures important for biofilm formation, are only produced at temperatures below 30 C in Escherichia coli K-12 strains. In this report, we show that E. coli K-12 can produce curli at 37 C when grown as a biofilm community. The curli-expressing strain formed more biofilms on polyurethane sheets than the curli-deficient strain under growth temperatures of both 25 C and 37 C. Curli are required for the formation of a three-dimensional mature biofilm, with characteristic water channels and pillars of bacteria. Observations by electron microscopy revealed the presence at the surfaces of the curli-deficient mutant in biofilm of flagella and type I pili. A wild-type curli-expressing E. coli strain significantly adhered to several lines of human uroepithelial cells, more so than an isogenic curlideficient strain. The finding that curli are expressed at 37 C in biofilm and enhance bacterial adherence to mammalian host cells suggests an important role for curli in pathogenesis.

Bacterial Adhesion↗

N-[18F]fluoroethylpiperidin-4-ylmethyl butyrate: a novel radiotracer for quantifying brain butyrylcholinesterase activity by positron emission tomography.

In Alzheimer's disease, cerebral cortical butyrylcholinesterase (BChE) activity is reported to be elevated. Our aim was to develop a novel (18)F-labeled tracer for quantifying cerebral BChE activity by positron emission tomography. With in vitro screening of N-[(14)C]ethylpiperidin-3- and 4-ylmethyl esters, N-[(14)C]ethylpiperidin-4-ylmethyl butyrate was selected as a lead for (18)F-labeling, affording N-[(18)F]fluoroethylpiperidin-4-ylmethyl butyrate. The (18)F-labeled butyrate showed the required properties for in vivo BChE measurement, that is, the lipophilic nature of the authentic ester, high specificity to BChE, a moderate hydrolysis rate, and the hydrophilic nature of the metabolite.

Acetylcholinesterase↗

N-[18F]fluoroethyl-4-piperidyl acetate ([18F]FEtP4A): A PET tracer for imaging brain acetylcholinesterase in vivo.

N-[(18)F]Fluoroethyl-4-piperidyl acetate ([(18)F]FEtP4A) was synthesized and evaluated as a PET tracer for imaging brain acetylcholinesterase (AchE) in vivo. [(18)F]FEtP4A was previously prepared by reacting 4-piperidyl acetate (P4A) with 2-[(18)F]fluoroethyl bromide ([(18)F]FEtBr) at 130 degrees C for 30 min in 37% radiochemical yield using an automated synthetic system. In this work, [(18)F]FEtP4A was synthesized by reacting P4A with 2-[(18)F]fluoroethyl iodide ([(18)F]FEtI) or 2-[(18)F]fluoroethyl triflate ([(18)F]FEtOTf in improved radiochemical yields, compared with [(18)F]FEtBr under the corresponding condition. Ex vivo autoradiogram of rat brain and PET summation image of monkey brain after iv injection of [(18)F]FEtP4A displayed a high radioactivity in the striatum, a region with the highest AchE activity in the brain. Moreover, the distribution pattern of (18)F radioactivity was consistent with that of AchE in the brain: striatum>frontal cortex>cerebellum. In the rat and monkey plasma, two radioactive metabolites were detected. However, their presence might not preclude the imaging studies for AchE in the brain, because they were too hydrophilic to pass the blood-brain barrier and to enter the brain. In the rat brain, only [(18)F]fluoroethyl-4-piperidinol ([(18)F]FEtP4OH) was detected at 30 min postinjection. The hydrolytic [(18)F]FEtP4OH displayed a slow washout and a long retention in the monkey brain until the PET experiment (120 min). Although [(18)F]FEtP4A is a potential PET tracer for imaging AchE in vivo, its lower hydrolytic rate and lower specificity for AchE than those of [(11)C]MP4A may limit its usefulness for the quantitative measurement for AchE in the primate brain.

Acetates↗

Performance evaluation of a hand-held, semiconductor (CdZnTe)-based gamma camera.

We have designed and developed a small field of view gamma camera, the eZ SCOPE, based on use of a CdZnTe semiconductor. This device utilises proprietary signal processing technology and an interface to a computer-based imaging system. The purpose of this study was to evaluate the performance of the eZ scope in comparison with currently employed gamma camera technology. The detector is a single wafer of 5-mm-thick CdZnTe that is divided into a 16x16 array (256 pixels). The sensitive area of the detector is a square of dimension 3.2 cm. Two parallel-hole collimators are provided with the system and have a matching (256 hole) pattern to the CdZnTe detector array: a low-energy, high-resolution parallel-hole (LEHR) collimator fabricated of lead and a low-energy, high-sensitivity parallel-hole (LEHS) collimator fabricated of tungsten. Performance measurements and the data analysis were done according to the procedures of the NEMA standard. We also studied the long-term stability of the system with continuous use and variations in ambient temperature. Results were as follows. INTRINSIC ENERGY RESOLUTION: 8.6% FWHM at 141 keV.LINEARITY: There was excellent linearity between the observed photopeaks and the known gamma ray energies for the given isotopes. INTRINSIC SYSTEM UNIFORMITY: For the central field of view, the integral uniformity and the differential uniformity were, respectively, 1.6% and 1.3% with the LEHR collimator and 1.9% and 1.2% with the LEHS collimator. SYSTEM SPATIAL RESOLUTION: The FWHM measurements made at the surface of the collimator were 2.2 mm (LEHR) and 2.9 mm (LEHS).CONTRAST TEST: The average S/N ratios (i.e. counts in the irradiated pixel divided by counts in the surrounding pixels) for the inner ring pixels (8)/outer ring pixels (16) using the LEHS collimator and LEHR collimator were 3.2%/0.2% and 3.7%/0.3%, respectively. COUNT RATE CHARACTERISTICS: We could not determine the maximum count rate and the 20% loss count rate from these data because the plateau was not reached while using the solutions measured. SYSTEM SENSITIVITY: The average acquisitions were 11,052 cpm/MBq (LEHR) and 28,590 cpm/MBq (LEHS). TEMPERATURE DEPENDENCE: The system displayed minimum corresponding shift in cps with temperature changes in the measured temperature range. We designed and developed a semiconductor-based gamma camera using CdZnTe. The basic performance of this camera compares favourably with the existing gamma camera technology that is deployed in the medical field today. The most significant differences include the spatial resolution, sensitivity, high count rate characteristics and energy resolution. We believe that this device will be of value for a number of clinical applications including sentinel node detection and radiopharmaceutical-guided surgery.

Cadmium↗

Photodynamic therapy of intestinal tumors with mono-L-aspartyl chlorin e6 (NPe6): a basic study.

BACKGROUND: To clarify the usefulness of the second-generation photosensitizer, mono-L-aspartyl chlorin e6 (NPe6), we examined the possibility of photodynamic diagnosis and photodynamic therapy for intestinal tumors in a mouse model. MATERIALS AND METHODS: NPe6 was intravenously administered to the tumor-bearing mice through the tail vein. The intestinal tumor sites were irradiated with a 664-nm diode laser at constant intervals after the administration of photosensitizers. The tumors were excised and fluorescence was observed in frozen sections by microscope. RESULTS: We observed the fluorescent image and calculated that the mean fluorescence intensity was significantly higher in the tumors than the normal mucosa during 6 hours (p < 0.05). The fluorescence of NPe6 was chiefly accumulated in the intestinal tumors as red fluorescence on the fluorescent microphotographic image. CONCLUSION: We conclude that NPe6 may be a valuable photosensitizer for the photodynamic diagnosis and photodynamic therapy of intestinal tumors.

Animals↗

Multiparameter analysis for discreet differential diagnosis of mucosa-associated lymphoid tissue lymphoma in the intestine.

BACKGROUND: The diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma in the intestine is occasionally difficult from histological examination on small biopsy specimens obtained by endoscopy. This study focused on unusual cases of reactive lymphoproliferative disorders in the intestine in order to make a differential diagnosis of MALT lymphoma. MATERIALS AND METHODS: Five patients were examined with regards to clinical symptoms, endoscopic findings and multiparameter analysis (the morphological examination using routine hematoxylin and eosin staining by light microscopy, immunophenotyping by flow cytometry (FCM), immunohistochemistry and genotyping of extracted DNA). RESULTS: All cases showed an aggregation of lymphocytes and one case showed similar features to lymphoepithelial lesions. Analyses of FCM and genetic rearrangements denied the monoclonality in all cases. Consequently, we considered that all cases should be diagnosed as reactive lymphoid hyperplasia and inflammatory change. CONCLUSION: Multiparameter analysis is useful in making an exact diagnosis of MALT lymphoma and therefore contributes to prevent unnecessary overtreatment.

Adolescent↗