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Fine-needle aspiration cytology (FNAC) is a specific and important test used for the diagnosis of thyroid gland cancer. We developed a thyroid gland phantom using original manufacturing techniques and direct three-dimensional (3D) printing. The aim of this study was to confirm the effectiveness of this phantom by collecting data to evaluate puncture training.Data from 45 ultrasonography-guided thyroid nodule FNAC procedures performed on our thyroid phantom were evaluated in our department. The first group comprised qualified physicians who specialized in thyroid gland treatment (group A; n = 10). The second and third groups comprised senior and junior residents (group B; n = 8 and group C; n = 12; respectively). The fourth group comprised students (group D; n = 15). We measured the times taken by these groups to complete each task.The skills of all participants in groups B, C, and D improved after using this phantom involving the major (parallel)- (0.47 ± 0.07) and short (orthogonal)-axes (0.52 ± 0.07) methods (P 0.001). The number of erroneous punctures decreased from 53 to 3.Our original phantom improved the puncture skills of students and junior doctors and was suitable as a tailored training model for practicing thyroid gland transfixion.

The radical copolymerization on α-substituted fluoroalkyl acrylate (FA) monomer bearing C4, C6, and C8 as perfluoroalkyl (Rf) groups, as well as the variation of α-substituents, hydrogen, methyl, and chlorine with styrene was investigated. Q-e values and monomer reactivity ratio of FA monomers were estimated. When the alpha position of FA monomer of C6 as Rf group was changed from −H to −CH3, the e value decreased from 0.85 to 0.60. The substituent of −Cl resulted in an e value of 1.06. The Q values were also markedly changed. When the alpha position was changed from −H to −CH3, the Q value increased from 0.38 to 0.79. The substituent of −Cl resulted in a Q value of 2.90. The copolymer composition of α-substituted FA monomers with stearyl acrylate (C18A) was simulated. The obtained results revealed that a chlorine substituent at the alpha position emphasizes the polymerization which would contribute to a novel material design containing a fluorine side chain in a monomer structure.

The purpose of the present study was to identify the structures of cannabidiol (CBD) metabolites during CO formation by human liver microsomes and human recombinant cytochrome P450 (CYP) enzymes. CBD was NADPH-dependently metabolized by human liver microsomes and human recombinant CYP enzymes. Less-polar metabolites were analyzed by gas chromatography–mass spectrometry monitoring, and their estimated molecular ions were m/z 286, 358 and 481 after non-derivatization, trimethylsilylation and pentafluorobenzyl oxime formation, respectively. We tentatively identified novel decarbonylated metabolites of CBD as keto-enol tautomers. Among eight major recombinant human CYP enzymes, only CYP3A4 catalyzed the formation of decarbonylated metabolites. CBD was biotransformed to two decarbonylated metabolites, an enol-form (cyclopentadienol structure), and a keto-form (cyclopentenone structure) by human liver microsomes and CYP3A4.

We previously reported the diversity of structure and integration sites of human T-cell leukemia virus type 1 (HTLV-1) provirus among different MT-2 cell lines. This raised the question as to whether cell phenotypes also differed among MT-2 cell lines. The influence of two different MT-2 cell lines (MT-2J and MT-2B) on the growth of the promonocytic leukemia cell line, U937, was investigated. Protein levels and mRNA expression of cytokines were also investigated. In addition, Western blot analysis of HTLV-1 regulatory proteins, Tax and HBZ, was also performed. Culture supernatant from MT-2B, but not MT-2J, cells showed marked suppressive effects on U937 cell growth. MT-2B showed high tumor necrosis factor (TNF)-α, TNF-β, and interferon (IFN)-γ both in protein levels of the culture supernatant and mRNA levels of the cells. Analysis using recombinant cytokines indicated that the suppressive effects of MT-2B were due, at least in part, to high levels of TNF-β and its synergic effects with IFN-γ in the culture supernatant. Protein levels of HTLV-1 Tax and HBZ were higher in MT-2B than those in MT-2J cells. These molecules have been reported to affect the cytokine production of HTLV-1 infected cells; therefore, the difference in these molecules may have accounted for the differences in cytokine production between MT-2J and MT-2B cells. Furthermore, because MT-2 cells showed a large variation of integrated HTLV-1 proviruses as well as cell phenotypes, it is important to exercise caution in the assessment and interpretation of experimental data from MT-2 cells.

∆9-Tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD), major psychoactive constituents of marijuana, induce potentiation of pentobarbital-induced sleep in mice. We have elucidated the mechanism of enhancement of the anesthetic effect of pentobarbital by cannabinoids. We carried out pharmacological experiment and cannabinoid1 (CB1) receptor binding assay using CB1 antagonists to clarify whether the CB1 receptor is involved in the synergism or not. The affinities of cannabinoids for the CB1 receptor in the mouse brain synaptic membrane were evaluated using a specific CB1 ligand, [3H]CP55940. Although the potentiating effect of ∆9-THC on pentobarbital-induced sleep was attenuated by co-administration of CB1 receptor antagonists, such as SR141716A and AM251, at a dose of 2 mg/kg, intravenously (i.v.) to mice, the CBD-enhanced pentobarbital-induced sleep was not inhibited by SR141716A. The inhibitory constant (Ki) values of ∆9-THC and CBD were 6.62 and 2010 nM, respectively, showing a high affinity of ∆9-THC and a low affinity of CBD for the CB1 receptor, respectively. A high concentration of pentobarbital (1 mM) did not affect specific [3H]CP55940 binding on the mouse brain synaptic membrane. These results suggest that binding of ∆9-THC to the CB1 receptor is involved in the synergism with pentobarbital, and that potentiating effect of CBD with pentobarbital may differ from that of ∆9-THC. We successfully demonstrated that ∆9-THC enhanced the anesthetic effect of pentobarbital through the CB1 receptor.

Four major phytocannabinoids (∆8-tetrahydrocannabinol, ∆9-tetrahydrocannabinol, cannabidiol, and cannabinol, 100 mg each) were dissolved in Duquenois reagent containing vanillin and acetaldehyde in ethanol, and concentrated hydrochloric acid was added. The chromophores derived from the four cannabinoids were characterized by mass spectrometry after dichloromethane extraction and partial purification by Florisil column chromatography with dichloromethane-ethanol solutions, using a unique replacement technique, which caused various modes of peak shifts in mass spectra giving information for structural elucidation. It was disclosed that there were three types of condensates, among which the structures of two condensates could be delineated, but one condensate remains to be clarified. To our knowledge, this is the first report to simultaneously propose the structures of the Duquenois reaction chromophores for the four major phytocannabinoids.

A human T-lymphotropic virus Type 1 (HTLV-1) positive cell line, MT-2, derived from human cord leukocytes co-culturing with adult T cell leukemia/lymphoma (ATL) cells is commonly used in HTLV-1 research; however, the details of provirus integrated in MT-2 genome have not yet been characterized. In this study, five types of HTLV-1 proviral sequences were detected in 11 different sites of the genome in a reference MT-2 cell line. The five types of HTLV-1 proviral sequences were one complete proviral genome, two types of proviruses with deletion of large internal viral sequences (5.3 and 3.9 kB), one provirus with a large deletion (6.2 kB) from 5'LTR to position 6257, and one provirus of LTR only. The provirus with identical deletion of large internal viral sequence (5.3 kB) was found to be integrated into six different sites (chromosomes). A complete provirus and three of four types of defective provirus were consistently detected in two other MT-2 cell lines cultured in different laboratories. Not only Tax/Rex RNA and HBZ RNA, but also the transcriptional product for a specific defective provirus, were detectable in all three MT-2 cell lines. Because it has been reported that defective provirus is frequently detected in ATL cells, these results may be important in understanding the mechanism of HTLV-1 proviral polymorphism, which may be related to leukemogenesis. In addition, the large variation in integrated HTLV-1 proviruses makes it important for researchers to exercise caution in their assessment and interpretation of results using MT-2 cell lines.

We recently reported that Δ9-tetrahydrocannabinol (Δ9-THC), the primary psychoactive constituent in marijuana, potently inhibits the catalytic activity of cytochrome P450 (CYP) 2C9.1, a wild-type variant. However, effects of CYP2C9 genetic polymorphisms on the inhibitory potency of Δ9-THC have not been investigated. In this study, in vitro inhibitory effects of Δ9-THC on catalytic activities of two major allelic variants, CYP2C9.2 and CYP2C9.3, were examined with the recombinant enzymes. Δ9-THC inhibited S-warfarin 7-hydroxylation, diclofenac 4′-hydroxylation, and tolbutamide 4-hydroxylation by CYP2C9.2 and CYP2C9.3 in a concentration-dependent manner. The IC50 values for the catalytic activities toward S-warfarin, diclofenac, and tolbutamide were 2.39, 1.04, and 1.12 μM, respectively, for CYP2C9.2, and 2.91, 1.38, and 1.09 μM, respectively, for CYP2C9.3. The inhibitory potencies against these mutant variants were similar to those against the wild-type variant. In contrast, Δ9-THC inhibited 7-methoxy-4-(trifluoromethyl)coumarin O-demethylase activity of CYP2C9.1, CYP2C9.2, and CYP2C9.3 to various extents, showing the IC50 values of 1.02, 4.20 and >10 μM, respectively. Our recent study showed that a preincubation of Δ9-THC in the presence of NADPH decreased the inhibitory effect on CYP2C9.1 activity. Then the effect of preincubation on Δ9-THC-mediated inhibition of S-warfarin 7-hydroxylation was investigated with CYP2C9.2 and CYP2C9.3. The preincubation of Δ9-THC with CYP2C9.2 attenuated the inhibitory effect of the phytocannabinoid, whereas preincubation with CYP2C9.3 did not. These results indicate that the inhibitory effects of Δ9-THC on CYP2C9 variants depend on the substrates used and the preincubation time.

Inhibitory effects of Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), and cannabinol (CBN) on the catalytic activities of human recombinant cytochrome P450 (CYP) 2A6 and CYP2B6 were investigated. Δ9-THC, CBD, and CBN noncompetitively inhibited coumarin 7-hydroxylase activity of recombinant CYP2A6 with the apparent K i values of 28.9, 55.0, and 39.8 μM, respectively. On the other hand, Δ9-THC, CBD, and CBN inhibited 7-benzoxyresorufin O-debenzylase activity of recombinant CYP2B6 in a mixed fashion with the K i values of 2.81, 0.694, and 2.55 μM, respectively. Because the inhibition of CYP2B6 by CBD was the most potent, investigation was conducted to determine which moiety of the CBD structure was responsible for the inhibition. Olivetol and d-limonene, the partial structure of CBD, inhibited the CYP2B6 activity to some extent. Inhibitory effects of CBD-2′-monomethyl ether and CBD-2′,6′-dimethyl ether attenuated with the number of methylations on the phenolic hydroxyl groups in the resorcinol moiety of CBD. Cannabidivarin, a CBD analogue having a propyl side chain, inhibited the CYP2B6 activity less potently than CBD possessing a pentyl side chain. Therefore, both structures of pentylresorcinol and terpene moieties of CBD were suggested to play important roles in the CYP2B6 inhibition. Δ9-THC, CBD, and CBN showed metabolism-dependent inhibition for CYP2A6 but not for CYP2B6. Furthermore, Δ9-THC and CBN were characterized as mechanism-based inhibitors for CYP2A6. The k inact and K I values of Δ9-THC were 0.0169 min−1 and 0.862 μM, respectively; the k inact and K I values of CBN were 0.00909 min−1 and 1.01 μM, respectively. These results indicated that Δ9-THC, CBD, and CBN showed differential inhibition against CYP2A6 and CYP2B6.

Δ8-Tetrahydrocannabinol (THC) and Δ9-THC were mainly oxidized on the pentyl side chain at the 4′-position by mouse brain microsomes. 5′-Hydroxy-THCs were also formed as minor metabolites. However, 11-hydroxy metabolites of THCs, which are major metabolites of the cannabinoids produced by mouse hepatic microsomes, were not detectable as the metabolites formed by mouse brain microsomes. Cytochrome P450 (CYP) enzymes involved in the brain microsomal metabolism of Δ8-THC and Δ9-THC were identified by using CYP-selective inhibitors. The 4′- and 5′-hydroxylations of THCs were strongly inhibited by ketoconazole and troleandomycin, the known inhibitors of CYP3A enzymes, but not by other isozyme-selective inhibitors, such as 7,8-benzoflavone (CYP1A), quinidine (CYP2D), and sulfaphenazole (CYP2C). These results indicate that Cyp3a enzymes are responsible at least in part for the metabolism of Δ8-THC and Δ9-THC by mouse brain microsomes. Our present results using mouse brain seem to support the idea that the mode of THC metabolism by CYP enzymes in human brain is different from that in human liver.

The independent administrative corporation Japan Agency for Marine–Earth Science and Technology (JAMSTEC) has developed a small light autonomous underwater vehicle (AUV) named marine robot experimental 1 (MR-X1).1 The motion control of MR-X1 is considered in this article. Since the dynamics of MR-X1 mainly depends on its own speed, the motion control is a nonlinear control system. We propose a new controller design method for this system using linear matrix inequalities (LMIs). This algorithm gives a solution as a linear matrix inequality, and can be adapted to solve many LMIs simultaneously. LMIs can be obtained by substituting several speeds into the dynamics of the MR-X1. The proposed controller, which can be derived from the solution of the LMIs, was adapted to MR-X1 and showed good performance in experiments.

sleeping time by 1.8 to 8.0 times as compared with the control solution with 1% Tween 80-saline. The ED50 values (mg/kg, i.v.) of 9α-OH-HHC and 8-OH-iso-HHC for the antinociceptive effect were 14.1 and 39.4, respec- tively. The present study demonstrated that CBD can be converted to ∆ 9 -THC and its related cannabinoids, 9α- OH-HHC and 8-OH-iso-HHC, in artifi cial gastric juice, and that these HHCs show ∆ 9 -THC-like effects in mice, although their pharmacological effects were less potent than those of ∆ Abstract Cannabidiol (CBD), a nonpsychoactive can- nabinoid, was found to be converted to 9α-hydroxy- hexahydrocannabinol (9α-OH-HHC) and 8-hydroxy- iso-hexahydrocannabinol (8-OH-iso-HHC) together with ∆ 9 -tetrahydrocannabinol (∆ 9 -THC), a psychoactive cannabinoid, and cannabinol in artifi cial gastric juice. These cannabinoids were identifi ed by gas chromatogra- phy-mass spectrometry (GC-MS) by comparison with the spectral data of the authentic compounds. Pharma- cological effects of 9α-OH-HHC and 8-OH-iso-HHC in mice were examined using catalepsy, hypothermia, pen- tobarbital-induced sleep prolongation, and antinocicep- tion against acetic acid-induced writhing as indices. The ED50 values (effective dose producing a 50% reduction of control; mg/kg, i.v.) of 9α-OH-HHC and 8-OH-iso- HHC for the cataleptogenic effect were 8.0 and 30.4, re- spectively. 8-OH-iso-HHC (10 mg/kg, i.v.) produced a signifi cant hypothermia from 15 to 90 min after admin- istration, although 9α-OH-HHC failed to induce such an effect at the same dose. However, both HHCs (10 mg/ kg, i.v.) signifi cantly prolonged pentobarbital-induced

Background: The standard procedure for sympathectomy is open surgery. The oblique retroperitoneal approach is popular because it provides good visibility, albeit at the expense of requiring a long skin incision. Chemical sympathectomy has been introduced as a less invasive means of achieving sympatholysis; however, this method is also associated with a significant incidence of incomplete block and transient denervation. Laparoscopic surgery is a new approach that simplifies various surgical procedures. The aim of our report was to evaluate the benefits of endoscopic retroperitoneal surgery for lumbar sympathectomies. Methods: Between March 1997 and April 2000, seven patients underwent laparoscopic lumbar sympathectomy in our department (all men, with an average age or 45.1 years). The predominant presenting symptoms were unilateral pain at rest and lower-extremity coldness. Symphaectomy was performed using a retroperitoneal approach on six patients and an anterior transperitoneal approach on one patient. After laparoscopic lumbar sympathectomy, skin thermometry was carried out on all patients. Results: The postoperative skin temperature of the affected leg rose to 36.6 ± 0.5°C, as compared to 33.8 ± 0.8°C preoperatively. After laparoscopic lumbar sympathectomy, none of the patients complained of neuralgia. All patients achieved sustained symptomatic relief, and no major postoperative complications were noted. Conclusions: Lumbar sympathectomy can be performed laparoscopically. Currently, our standard technique is the retroperitoneal approach. More clinical experience and long-term follow-up will ultimately determine if this will become the procedure of choice. However, we believe that a learning period is necessary for this technique to be fully mastered.

We have devised a method of determining the optimal value of both the refractive index n and the diameter D of a transparent cylinder by the scattering intensity pattern over a wide range of scattering angle. We have shown that the method is stable to small variations of data for the sample with D#x2272;10#x03BB; (wavelength) and could specifically determine the parameters of a spider#x0027;s thread as n = 1.520 (#x2212;0.033, #x002B;0.033), D=0.564 (#x2212;0.009, #x002B;0.011)#x03BC;m for #x03BB; = 632.8 nm.

Metabolism of cannabinol (CBN) was studied in vitro using hepatic microsomes from human livers. The metabolites formed were analyzed by thinlayer chromatography (TLC) and identified by gas chromatography-mass spectrometry as their trimethylsilyl derivatives. 11-Hydroxy-CBN, the major metabolite, was detected together with a smaller amount of another mono-hydroxylated metabolite. The minor metabolite was identified as 8-hydroxy-CBN, after comparing its Rf value by TLC, retention time by GC, and the mass spectrum with those of the authentic compound. 8-Hydroxy-CBN was confirmed to be a new metabolite of CBN formed by human hepatic microsomes.

The present study was conducted to identify cytochrome P450 3A (CYP3A) inhibitory components of Hyuganatsu, Citrus tamurana Hort., by investigating the effects on midazolam 1'-hydroxylase activity of human liver microsomes. As a consequence, limonin and nomilin were identified as CYP3A inhibitors from the endocarp of Hyuganatsu.

Effects of pentobarbital pellet implantation on [3H]baclofen binding in the frontal cortex of cerebellum of rat brains were examined. In the frontal cortex, pentobarbital tolerance caused an increase in the number of binding sites (Bmax) without changing their affinity (KD). Twenty-four hours after withdrawal of the pentobarbital pellets, there was a significant increase in the KD and Bmax values. Cerebellar binding, in contrast, was not significantly changed in any of the treatment groups. Addition of 1 mM of pentobarbital directly to binding assays using cortical membrane produced as increase in KD without a change in Bmax. In vitro, pentobarbital affected neither the KD nor the Bmax in the cerebellar [3H]baclofen binding. These results suggest that like the GABAA receptor, [3H]baclofen binding to the GABAB receptor in rat frontal cortex was affected by pentobarbital tolerance and dependence, and that there are regional differences in the properties of the GABAB receptor.

Preparation of Monodispersed Poly(methyl methacrylate) Particle in the Size of Micron Range

A number of investigators have reported about heavy metal contents in food, blood, urine, and animal tissues, including bone, hair, feather, and tooth. However, few data concerning calculi are reported as yet. Heavy metal contents in the calculi might reflect the level of metals absorbed from respiratory tract, skin and intestine. When absorbed metals from respiration are distributed in blood, a part of cadmium is accumulated in liver and kidney, and of lead is in bone, annular vessel and kidney. The remainder is excreted in the urine through the urinary tracts. From intestine, they are distributed by the blood to the liver, and excreted in the urine in the same manner of respiration. It is well known that renal calculi are produced in the urinary tract. The present study is focused on the contents of cadmium, copper, zinc and lead in human renal calculi, samples collected from Hokuriku which is one of the most cadmium polluted areas and from Chugoku which is recognized as a non-polluted one in Japan.