Two phenol-based compartmental ligands of the “end-off” type, 2,6-bis{N-[2-(dimethylamino)ethyl]iminomethyl}-4-methylphenol (HL1) and 2-{N-[2-(dimethylamino)ethyl]iminomethyl}-6-{N-methyl-N-[2-(dimethylamino)ethyl]aminomethyl}-4-bromophenol (HL2), have been used to form [Ni2(L1)(AcO)(NCS)2(MeOH)] (1), [Ni2(L1)(AcO)2(MeOH)]BPh4 (2), [Ni2(L2)(AcO)(NCS)2(MeOH)] (3), [Ni2(L2)(AcO)2]BPh4 (4), and [Ni2(L2)(NCS)3(MeOH)] (5). X-ray crystallographic studies were done for 2−5. 2:  triclinic, space group P1̄, a = 13.613(3) Å, b = 16.475(4) Å, c = 11.307(4) Å, α = 99.90(2)°, β = 104.16(2)°, γ = 109.01(2)°, V = 2253(1) Å3, Z = 2. The complex cation has a dinuclear core triply bridged by the phenolic oxygen of (L1)- and two acetate groups in the syn-syn mode. One Ni has a six-coordinate geometry together with a methanol oxygen. 3: triclinic, space group P1̄, a = 10.167(1) Å, b = 16.119(2) Å, c = 9.472(3) Å, α = 103.53(2)°, β=100.91(1)°, γ = 85.62(1)°, V = 1481(1) Å3, Z = 2. A pair of Ni ions are bridged by the phenolic oxygen of (L2)-, an isothiocyanate nitrogen, and an acetate group. The sixth position of one Ni is occupied by a methanol oxygen and that of the other Ni by isothiocyanate nitrogen. 4:  monoclinic, space group P21/n, a = 15.146(2) Å, b = 9.442(3) Å, c = 30.844(2) Å, β = 93.427(9)°, V = 4402(1) Å3, Z = 4. Two Ni ions are bridged by the phenolic oxygen of (L2)- and an acetate group. The Ni bound to the iminic pendant arm is nearly planar whereas the Ni bound to the aminic pendant arm is of six-coordination together with a bidentate acetate group. 5:  monoclinic, space group C2/c, a = 26.744(5), b = 10.323(4) Å, c = 21.785(6) Å, β = 94.73(2)°, V = 5993(3) Å3, Z = 8. Two Ni ions are bridged by the phenolic oxygen of (L2)- and an isothiocyanate nitrogen. The Ni bound to the iminic pendant arm is of five-coordination along with an isothiocyanate nitrogen. The Ni bound to the aminic pendant arm has a six-coordinate geometry together with a methanol oxygen and an isothiocyanate nitrogen. 1−5 were examined regarding their ability to bind urea, and 4 and 5 were shown to form [Ni2(L2)(AcO)2(urea)]BPh4 (4‘) and [Ni2(L2)(NCS)3(urea)] (5‘), respectively. 5‘ crystallizes in the monoclinic system, space group P21/n, with a = 11.709(5), b = 15.100(4), c = 17.548(5) Å, β = 95.58(3)°, V = 3087(1) Å3, and Z = 4. Its dinuclear core is very similar to that of 5 except that the methanol of 5 is replaced by a urea molecule.

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Approximately 10% of Japanese alcoholics develop their disease despite having an inactive form of aldehyde dehydrogenase-2 (ALDH2), 1 known as a genetic deterrent of heavy drinking due to adverse reactions after drinking.2 Such alcoholics are considered to be advantageous in genetic research because they should show reduced heterogeneity and possess genetic factors conferring susceptibility to alcohol dependence. Examination of the −1438 A/G polymorphism of the serotonin 2A (5HT2A) receptor gene in 225 Japanese alcoholics with inactive ALDH2 revealed the presence of significantly more of the G allele than was found in 361 control subjects. The frequency of the G allele in 282 alcoholics with active ALDH2 fell between the G allele frequencies of controls and subjects with inactive ALDH2. These data suggest that although the effect is relatively small, genetic variability in the 5HT2A receptor is involved in the development of alcohol dependence.Genetic factors play pivotal roles in the development of alcohol dependence, as twin, adoption studies consistently show. These factors may involve genetic variation in neurotransmission. Recently, Collier and colleagues 3 reported a positive association between a biallelic polymorphism (−1438 G/A) in the promoter region of the serotonin 2A (5HT2A) receptor gene and anorexia nervosa. They reported that the frequency of an A allele was overrepresented in patients with anorexia nervosa compared with that in controls. However, evidence against these findings 4 makes them controversial.Because (1) several lines of evidence have shown that the function of the serotonergic system is closely related to the alterations in food and ethanol intake in both animals and humans, 5-7 and (2) eating disorders are often coincident with alcohol dependence, 8 we speculate that the 5HT2A receptor gene promoter polymorphism confers genetic susceptibility to alcohol dependence. To explore this hypothesis, we have investigated possible associations between 5HT2A receptor gene promoter polymorphism and alcohol dependence.The most likely model of inherited alcohol dependence involves the interaction of multiple genes that have minor effects and sociocultural factors in the environment, which leads to the development of the disease in genetically susceptible individuals. One of the major obstacles in identifying genes that produce minor effects is the heterogeneity of the disease to be examined. To overcome this problem, we studied alcoholics with inactive aldehyde dehydrogenase-2 (ALDH2), which is encoded by either heterozygous ALDH2*1/2*2 or homozygous ALDH2*2, a welldefined genetic risk factor that lowers the risk for alcohol dependence.2,9,10 The heterogeneity of the disease is considered to be relatively low in this genetically defined subgroup, compared with the entire alcoholic population.In addition, individuals who have become alcoholic despite their inactive ALDH2 probably have one or more factors that increase their susceptibility to alcohol dependence. If 5HT2A receptor gene polymorphis...

A high-performance liquid chromatographic method has been developed for the simultaneous analysis of the 12 phenothiazines (chlorpromazine, fluphenazine, levomepromazine, perazine, perphenazine, prochlorperazine, profenamine, promethazine, propericiazine, thioproperazine, thioridazine and trifluoperazine) in human serum using HPLC/UV. The separation was achieved using a C(18) reversed-phase column (250 mm x 4.6 mm I.D., particle size 5 microm, Inersil ODS-SP). The mobile phase, consisting of acetonitrile-methanol-30 mM NaH(2)PO(4) (pH 5.6) (300:200:500, v/v/v), was delivered at a flow rate of 0.9 mL/min and UV detection was carried out at 250 nm. The recoveries of the 12 phenothiazines spiked into serum samples were 87.6-99.8%. Regression equations for the 12 phenothiazines showed excellent linearity, with detection limits of 3.2-5.5 ng/mL for serum. The inter-day and intra-day coefficients of variation for serum samples were commonly below 8.8%. The selectivity, accuracy and precision of this method are satisfactory for clinical and forensic purposes. This sensitive and selective method offers the opportunity for simultaneous screening and quantification of almost all phenothiazines available in Japan for the purposes of clinical and forensic applications.

A homozygous gene deletion at the GST1 locus of genomic DNA isolated from peripheral blood was investigated for its relationship with several types of cancer using the polymerase chain reaction (PCR) technique. DNA samples were prepared from blood obtained from 128 healthy blood donors and 150 patients with cancer or chronic hepatitis. PCR primers were prepared based on the human cDNA sequence and the intron/exon sequences of the rat Yb2 gene. The amplified sequence between exons 5 and 6 including intron 5 showed very clearly the presence of absence of the GST1 gene, after electrophoresis in a 2% agarose gel. Segregation of the presence and absence of PCR product from samples of twins and their parents indicated that presence involves homozygous or heterozygous normal GST1 genotypes while absence involves only homozygous gene deletion. The patients with stomach cancer had a significantly higher frequency of gene deletion than did the healthy controls (P < 0.005). Thus, GST1 deletion may be a possible genetic marker for early detection of a group at high risk of stomach cancer.