Ten furostanol saponins were isolated as five pairs of 25R and 25S epimers from the fresh rhizomes of Polygonatum kingianum. Seven of them were identified as new compounds, (25S)-kingianoside (2), (25S)-kingiano-side C (4), (25R,)-hydroxylwattinoside C (), kingianoside (7), (25S)-kingianoside (), kingianoside () and (25S)-kingianoside (10), together with three known saponins, kingianoside C (1), kingianoside (3), and -hydroxylwattinoside C (6). The structures of the new saponins were determinded by detailed analysis of their 1 and 2 NMR spectra, and by comparison of the spectral data with those reported.

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Mycestericins (1), (3), (2) and G (4), new immunosuppressants, were isolated from the culture broth of Mycelia sterilia ATCC 20349. The immunosuppressive activities of 1 and 2 exhibited an IC_<50> of 16nM and 120nM against mouse allogeneic mixed lymphocyte reaction (MLR), respectively, while 3 and 4 exhibited an IC_<50> of 13nM and 370nM, respectively. The proposed structures were unambiguously confirmed by spectroscopy, chemical evidence and total synthesis. Their absolute configurations have been determined by comparison of their CD spectra with those of synthetic compounds (R and S)- prepared from methyl (2S, 4R)-2-tert-butyl-3-formyl-oxazolidine-4-carboxylate () and stearoyl chloride. Thus, mycestericins (1) and (2) were assigned to be 2 (S), 3 (S) configurations, while mycestericins (3) and G (4) were 2 (S), 3 (R) configurations. The first total synthesis of mycestericins have been achieved from and 1,-octanediole (10). The alkyl chain moiety 21 was prepared in 12 steps from 10 by straightforward reactioin. The key intermediate obtained from and 21 could be converted to the desired final compounds. Stereoselective reduction of the ketone with Zn(BH_4)_2 or NaBH_4 provided the (R)-hydroxy 23, the protecting groups of which were removed with 10% MeOH in CF_3COOH, followed by hydrolysis of 24 to give mycestericin (3). On the other hand, mycestericin (1) was synthesized from by deprotection, followed by reduction of 25 with Me_4NBH(OAc)_3 and then hydrolysis of 26. Hydrogenation of mycestericin (1) and (3) provided the corresponding (2) and G (4).

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This study aimed to determine the prevalence of fecal carriage of extended spectrum β-lactamase (ESBL) and/or plasmidic AmpC β-lactamase (pAmpC) producing Escherichia coli among dogs (n=428) in Turkey. Polymerase chain reaction (PCR) and sequencing were used to characterize genes encoding β-lactamase and plasmid mediated quinolone resistance (PMQR). Antimicrobial susceptibility testing and PCRs for virulence genes and phylogenetic groups were also performed. Cefotaxime resistant

. coli isolates were detected in 95 (.2%) of the swab samples. Sequencing analysis results showed occurrence of various β-lactamase genes: bla_CTX-M-15 (62), bla_TEM-1b (42), bla_CMY-2 (), bla_CTX-M-3 (16), bla_CTX-M-1 (15), bla_OXA-1 () and bla_SHV-12 (3) alone or in combination. The most frequently encountered phylogenetic group was group A₁ (35.%), followed by group (.1%), B1 (15.%), (.%), A₀ (7.4%), (.3%) and B2₃ (4.2%), respectively. PMQR genes, aac(6’)-Ib-cr, qnrS1 and qnrB10 were detected in 25.3, 10. and 1.1% of the isolates, respectively. While all isolates were susceptible to imipenem and amikacin, resistance rates to non-β-lactam antibiotics ranged from 20.0% for tobramycin to 56.% for tetracycline. The virulence genes were only detected in 34 (36.2%) of the isolates and this isolates carried single or various combination of virulence genes of iucD, papC, papE, -A and eaeA. Four isolates were identified as human virulent pandemic CTX-M-15 producing

E

. coli clone O25b:ST131/B2. To the best of our knowledge, this is the first study to show fecal carriage of ESBL/pAmpC type β-lactamase producing

E

. coli isolates among dogs in Turkey.

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Vibrio parahaemolyticus is a prevalent food-borne pathogen in Taiwan, Japan and other Asian countries. This work presents a novel ribotyping method for the molecular epidemiological examination of this pathogen. Genomic DNA was fragmented by HindIII digestion and hybridized with cDNA probe for Escherichia coli 16S and 23S RNA genes. A total of 121 isolates obtained from outbreaks during 1992 and 1994 in Taiwan were characterized by this ribotyping method. Four to seventeen restricted fragments were visualized in these isolates. After hierarchical cluster analysis, these isolates were grouped into thirty different ribotypes. In addition, A3, A7, 3 and 1 were the major ribotypes, consisting of .3, 13.2, .1, and .3% of the isolates, respectively. A, , , G and B were the major groups, consisting of 46.2, 14.0, .1, 6.7, and 6.7% of the isolates, respectively. The discriminatory ability of this ribotyping method, as determined by Simpson's index of diversity, was 0., which closely resembled that of a previously reported pulsed-field gel electrophoresis method.

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Thirty-six patients (19 males, 17 females: atypical schizophrenia; 3, typical schizophrenia; , depression; 11, neurosis and other psychiatric disorders; ) were operated on according to orbitoventromedial undercutting by Hirose. In all cases, the Rorschach test was carried out and daily behaviors were studied. Thirty-one scales of the test were subjected to multivariate analysis whereas the behaviors were evaluated according to the following criteria, i.., A: recovered or symptom free, B: markedly improved, C: moderately improved, : slightly improved and : not improved. The following results were obtained.
1) The evaluation of behaviors is as follows. A: 12 cases, B: , C: , : 6, : none.
2) It was found that scores of +106% and R+106% scales were significantly higher after the operation than before; that correlation coefficients between the scores before and after the operation were considerably high.
3) Factor analysis followed by varimax rotation was carried out. Six factors were extracted, i.., (1) sensitivity to emotional stimuli, (2) ego-strength, (3) obsessional rigidity, (4) reaction time, () anxiety and tension and (6) empathy. It was revealed that 2 was high in atypical schizophrenia, depression and neurosis, and that 2 and 6 were significantly different in terms of the factor scores among the four groups A, B, C and ; 2 was highest in A, and lowest in regardless of whether it was before or after the operation. 6 showed high scores in both A and C, and low in .
4) Multiple discriminant analysis was applied to the data of the Rorschach test before the operation, by classifying 36 subjects into the four groups A, B, C and . As a result, high rates of correct diagnosis were obtained, i.., 100% for A, 78% for B, 56% for C and 100% for . When the groups C and were combined into one group (C+) the highest percentage (100%) was seen in A, followed by B (89%) and C+ group (87%). When the groups A and B were combined into one group (A+B), the percentages of correct diagnosis were 81% for A+B, and % for C+.
In conclusion, it can be said that scales of the Rorschach test have been proved to be valid for predicting mental and physical states after the orbito-ventromedial undercutting.

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Reactions of nor-diterpenoid dilactones isolated from Podocarpus plants have been investigated. The 7: ,: 11-dienolide type [C] dilactones, the least available but biologically the most active members, are mainly derived from naturally abundant dilactone components of α-pyrone type [A] and 7: -epoxy-: 11-enolide type [B] for total-synthetic and biological purposes. From nagilactone (), for example, a combined sequence of hydrogenolysis of 7: -epoxide group and dehydration gives nagilactone (7), 3β-hydroxynagilactone () and 2: 3-dehydronagilactone (19), which have been found from natural sources. From nagilactone A (1), photo-hydration and concomitant double bond migration of its acetate results in a lactol (), which is reduced to 1β-hydroxynagilactone (), another natural type [C] dilactone. Derivation of the type [A] or [B] from others is not successful. Some attempts for conversion of the ring A functional groups have also been studied.

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Four new sterols, , 6α-epoxy-(, 24R)-ergosta-(14), -diene-3β, 7β-diol (1), (, 24R)-ergosta-, -diene-3β, , 6β, 7α-tetrol (2), (, 24R)-ergosta-7, (11), -triene-3β, , 6β-triol (3) and 3β, , 6β-trihydroxy-(, 24R)-ergost--en-7-one (4), have been isolated from the fruit bodies of Grifola frondosa (FR.) S. . GRAY (Polyporaceae)together with fourteen known ones (-18), of which two ( and 6) are reported for the first time from a natural source. The structures of these compounds were elucidated on the basis of spectral data.

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A long term follow-up of patients after antero-lateral partial vertebrectomies (ALPV) was performed using patient charts and questionnaires. During the past 15 years, ALPV has been performed on 159 patients with cervical spinal disorders. Among them, 136 patients whose survey was performed more than 1 year ago were selected. 92 were male and 44 were female. Their ages ranged from 41 to 82, and the average age was 63.1. The follow-up period was from 1 to 14 years (the average being 3. years). Pathology included spondylosis 119, OPLL 31, canal stenosis and combined lesion cases. Surgical resuts were evaluated using a grade scale (excellent ; , good ; G, fair ; , poor ; P and dead ; ). At discharge, group was 40.2%, G was 51.%, was 7.2%, P was 0%, was 0.7%. At the end of the follow-up period was 36.%, G was 35.7%, was 20.2%, P was 7.1% and dead was .%. None of the deaths were related to the surgery. However, the score obtained from the Neurosurgical Cervical Spinal Scale were essentially consistent. Results of the questionnaire showed that 61.4% of the patients were satisfied, 30.1% were fairly satisfied and only .4% were dissatisfied. Dissatisfied cases included 2 cases of surgical failure but most of them were related to the progressive worsening of other lesions such as thoracic, lumbar spinal lesions or peripheral neuropathy. In 2 cases reoperation was performed, one anterior fusion with fibular strut graft for kyphoscoliosis and the other anterior fusion with a mini-plate for a fracture of the lamina and slippage of the vertebral body. In some cases, weakness of the C root area was encountered but most of these were resolved in a few months. Radiologically, the bony defects of the vertebral body were observed to become smaller, namely they were replaced by new growth of bone slowly in all cases. Thus, ALPV seems to be a useful surgical procedure for multilevel cervical spinal disorders.

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 The stability of

‒tetrahydrocannabinol acetate (‒THC‒OAc) and ‒tetrahydrocannabinol acetate (‒THC‒OAc) in -liquid during storage was investigated. ‒THC‒OAc liquids in cartridges were stored at 80℃ or 30℃ for 28 days. The relative concentrations of cannabinoids in the liquids were measured by gas chromatography with flame ionization detection. ‒THC‒OAc decreased during storage at either temperature. ‒THC, a minor impurity, also decreased. ‒THC‒OAc liquid in a cartridge was stored at 80℃ for 57 days. The concentration of ‒THC‒OAc and ‒THC, a minor impurity, did not change during that time. Cannabinol acetate increased in all liquids, and unknown products were also detected by gas chromatography/mass spectrometry (GC/MS). The ‒THC‒OAc and ‒THC‒OAc liquids were subjected to GC/MS to detect representative diluents, glycerol, propylene glycol, and polyethylene glycol 400, but none of these were detected.

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Repetitive liquefactions in angular and subangular gravels from an alluvial fan, in the case of two earthquakes with accelerations lower than that of a former which had caused liquefaction some months before, are described. The liquefaction took place from the surface, down to a depth of approximately 10 m. Water laden with sediments spouted out for some tens of minutes after the strong motion ceased. Knowledge of the grain size distribution of the sediments inside the body of the alluvial fan roughly defines the areas of the fan prone to future liquefaction. Non-repetitive liquefaction in overconsolidated fine fluvio-lacustrine sand of glacial origin at the unusual depth of 14 m to 16 m is also described. From the observation of sand lifted up for 10 m inside a large diameter well, and of that which spouted out from several microvents, it was estimated that extra-pore pressure was close to lithostatic conditions. Nevertheless, modeling of intrinsic pore pressure buildup on the DESRA2 programme gives lower values than the experimental one. Geotechnical characteristics of the 12 m-thick sandy stratum indicate that the upper part is unusually soft, either due to water circulation or past repetitive liquefactions which prevented reconsolidation. It is suggested that excess pore pressure generated by the earthquake was also due to redistribution of pressure from adjacent sediments.

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Three new azaphilone derivatives designated falconensins (), (6), and G (7) were isolated from the mycelium o Emericella falconensis, along with falconensins A (1), B (2), C (3), (4), and H (), and three hopane-type triterpenes, zeorin (), hepane-7β, -diol (10), and hopane-6α, 7β, -triol (11). The structures of -7 were confirmed by spectroscopic investigation and chemical correlations. The absolute stereochemistry of falconensins A (1) to G(7) was also established.

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Six new cembranoids sarcophytol P (3), R (4), S (), K (), (11), and T (13) were isolated from the soft coral Sarcophyton glaucum. Sarcophytol P (3) was shown to be the 20-hydroxy derivative of the major component sarcophytol A (1), and afforded the cyclization product 6 in CHCl_3 at room temperature, in a same way as in 1. Sarcophytols R (4) and S () were correlated to 1, by conversion of its 7R,R and 7S,S epoxide derivatives. Sarcophytol K() was a 13, 14-dihydroxycembranoid having a 1,3Z-diene moiety. The absolute configuration of and its 1Z,3- and 1Z,3Z-isomers sarcophytol B (2) and J (10) were determined by circular dichroism study of their bis-p-dimethylaminobenzoate derivatives. Sarcophytols (11) and T (13) were 1- and 1,3Z-isomers of 1. Compound 11 showed characteristic broadening of the ^1H-NMR chemical shifts, due to the restricted conformational interconversion. Using the three cembranoids sarcophytols (11, 1,3), N (15, 1Z,3Z) and T (13,1,3Z), spontaneous autoxidation-cyclization, in CHCl_3,was examined, in order to compare the stereochemical course of the reaction with that of 1 (1Z,3), which affords trans-fused bicyclo[.3.0]tetradecene systems. The 1,3Z-isomer 13 gave the same cyclization product 18, as in the reaction of 1, even though it is isomeric at C-1,3. The 1Z,3Z isomer 15 gave 19, in consequence of the reversed geometry at C-3 of 15. The 1,3-isomer (11) gave the bicyclic product , having an antipodal fusion as compared with 19. This was confirmed by PCC oxidation of 19 and , giving enantiomeric ketones 23 and 24 respectively. The 1(14)-epoxide 26 was shown to be the immediate precursor of , and acounted for the inversion of the geometry at C-1 of the cyclization product. Compound 26 is isomeric with the epoxide 17 derived from 1. The epoxide 17 is the postulated precursor in the conversion of 13 to 18. It is noteworthy that the mode of antipodal fusion of the cyclopentane rings, in 18 and , was controlled by the chirality of the epoxy rings. The C-14 hydroxyl group participates in the transannular cyclization, but was found not to be the requisite functional group for the reaction. Similar treatment of cembrene C (30), the parent hydrocarbon of 1, also reacted in CHCl_3 giving the bicyclic product 32.

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Following the characterization of licorice-saponins A3 (2), B2 (3), and C2 (4), the chemical structures of licorice-saponins 3 (), 2 (6), 3 (7), G2 (), H2 (), J2 (10), and K2 (11), seven of the ten oleanane-type triterpene oligoglycosides isolated from the air-dried roots of Glycyrrhiza uralensis FISCHER collected in the northeastern part of China, were investigated. On the basis of chemical and physicochemical evidence, the structures of licorice-saponins 3, 2, 3, G2, H2, J2, and K2 have been determined to be expressed as 3β-[α-L-rhamnopyranosyl(1→2)-β--glucuronopyranosyl(1→2)-β--glucuronopyranosyloxy]--acetoxyolean-12-en-30-oic acid (), 3-O-[β--glucuronopyranosyl(1→2)-β--glucuronopyranosyl]glabrolide (6), 3-O-[α-L-rhamnopyranosyl(1→2)-β--glucuronopyranosyl-(1→2)-β--glucuronopyranosyl]-11-deoxoglabrolide (7), 24-hydroxyglycyrrhizin (), 3-O-[β--glucuronopyranosyl-(1→2)-β--glucuronopyranosyl]liquiritic acid (), 24-hydroxy-11-deoxoglycyrrhizin (10), and 3β-[β--glucuronopyranosyl(1→2)-β--glucuronopyranosyloxy]-24-hydroxyoleana-11, 13(18)-dien-30-oic acid (11), respectively.

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Low molecular weight glutenin subunits are important components of wheat storage proteins, which play an important role in determining end-use quality of common wheat. A newly established matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) procedure was used to analyze 478 landraces of bread wheat collected from the Yangtze-River region in China. Results indicated that 17 alleles at three loci: Glu-A3, Glu-B3 and Glu-

were identified, resulting in 87 different allele combinations. Of the 17 alleles detected at all the Glu-3 loci, five belonged to Glu-A3, seven to Glu-B3 and five to Glu- locus. MALDI-TOF-MS indicated Glu-A3a/c was present in 72.%, Glu-A3b in .4%, Glu- in .4%, Glu- in .2% and Glu- in 3.6% lines. Seven types of alleles were identified at the Glu-B3 locus: Glu-B3

d

/i (25.%), Glu-B3b (21.3%), Glu-B3c (16.%), Glu-B3h (13.%), Glu- (.4%), Glu-B3a (.2%), and Glu-B3g (.2%). Five types of Glu- alleles were detected: Glu- (58.4%), Glu- (.6%), Glu- (15.%), Glu- (3.3%) and Glu- (0.2%). Four new alleles that showed abnormal MALDI-TOF spectrum patterns were identified at the Glu-A3 and Glu-B3 loci. A detailed study is needed to further characterize these alleles and their potential usage for wheat improvement.

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A full account is given of the chemical behavior observed for 7, -dialkyladeninium salts (16). On treatment with boiling 1N aqueous NaOH for 60min, 16a, b, , (X=I), 16c (X=Br), and 16 (X=ClO₄) rearranged to isomeric N⁶, 7-dialkyladenines (21a-) in 50-91% yields. Treatment of the salts with 0.N aqueous Na₂CO₃ at room temperature for 30-90min or with Amberlite CG-400 (OH^-) in H₂O at room temperature gave the ring-opened derivatives a- (in the trans-formamide form) in 56-83% yields, and rate constants for the ring-opening reactions of 16a, b, -g (X=ClO₄) and 16c (X=Br) leading to a-g were determined in H₂O at pH .84 and ionic strength 0.50 at 25°C. Cyclization of a with NaH in AcNMe₂ at room temperature or with boiling 1N aqueous NaOH produced 21a in 84% or 72% yield, respectively.In solution, the trans-formamides seemed to transform slowly into the cis-formamides 23, attaining equilibria. The existence of such an equilibrium in or Me₂SO- at 25°C or in H₂O at pH .84 and ionic strength 0.50 at 25°C was kinetically confirmed in the case of a, and the mechanism of the rearrangement of 16 to 21 through is discussed on the basis of the above kinetic results and Deslongchamps' theory of stereoelectronic control. On treatment with NaBH₄ in MeOH at room temperature, 16a (X=I) furnished the 7, -dihydro derivative 28 (84% yield), which slowly decomposed in H₂O at 60°C to give a in 49% yield.The 7, -dialkyladeninium salts (16) were found to be obtainable from N'-alkoxy-1-alkyl--formamidoimidazole-4-carboxamidines () through an alternative synthetic route : Alkylations of with alkyl halides in HCONMe₂ in the absence of base, followed by hydrogenolysis of the N'-alkoxy group and cyclizatio (or vice versa) produced 16 in acceptable yields. In order to interpret the proton nuclear magnetic resonance spectrum of a, the 2-deuterated species 26 was also synthesized from 24 via 25 and 27.

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要約：血友病は血液凝固第VIII 因子遺伝子（），第IX 因子遺伝子（）中の多種多様な遺伝子変異によって引き起こされる．これまで患者の病因遺伝子変異の解析は，1）エクソンとその近傍のPCR 増幅とシークエンスによる点変異や小規模な欠失・挿入の検出，2）MLPA（Multiplex Ligation-dependent Probe Amplification）による大規模な欠失・挿入の検出，3）ロングPCR によるX染色体逆位の検出，が行われてきた．しかし近年，身近になった次世代シークエンス（NGS）がこれらの解析に取り入れられるようになってきた．折りしも血友病の医療は，個別化医療に向かいつつある．またゲノム編集による遺伝子治療も臨床応用に向けて着実な進歩をみせている．このような状況下，個々の患者の責任遺伝子を中心としたジェノタイプの把握にNGS 解析の活用が期待されている．

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