IAN5 polymorphisms are associated with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a representative autoimmune disease, which is frequently associated with lymphopenia. Biobreeding (BB) rat is a typical animal model which develops autoimmune diseases with lymphopenia which results from a frame-shift mutation in the immune-associated nucleotide (IAN) 5 gene. IAN5 is involved in the regulation of T-cell activation and survival. To examine the association of IAN5 gene with SLE, we scrutinised the single nucleotide polymorphisms (SNPs) in the IAN5 gene. We conducted a case-control study where 132 SLE patients, 505 rheumatoid arthritis (RA) patients, and 546 controls were genotyped for four SNPs in the IAN5 gene. Two SNPs (+2071C > T and +2677G > A) were associated with susceptibility to SLE (P = 0.040 and 0.045, respectively), and -4432G > A SNP was associated with the development of leukopenia (P = 0.028) and the requirement of steroid pulse therapy (P = 0.040) in SLE patients. Haplotype analyses showed that Ht1(CTCG) was associated with susceptibility to SLE (P = 0.036), and Ht4(ACCG), Ht5(ACTA) and Ht6(GCCG) were associated with the development of nephritis (P = 0.017, 0.019, 0.022, respectively). In conclusion, the IAN5 polymorphisms were associated with susceptibility to SLE and the development of clinical disease manifestations in a strictly Korean population.

Photochemical and photobiological properties of new bispsoralen derivatives (Bis[PsCn]PIP, n = 4, 6, 8).

Bispsoralen derivatives possessing two psoralens and one piperazine molecule, 1,4-bis[n'-(8-psoralenoxy) alkyl] piperazine (Bis[PsCn]PIP, n = 4, 6, 8), show high water solubility, efficient intercalation into DNA and good photocrosslinking efficiency of DNA. Bis(PsC4)PIP shows high lethality on bacteriophage T7 and can effectively inhibit the amplification of DNA by stopping the polymerase chain reactions in a short period of irradiation time.

A case of parasymphyseal and associated insufficiency fractures of pubic rami in a patient with mixed connective tissue disease.

Parasymphyseal insufficiency fractures are uncommon. Furthermore, none have been reported in systemic rheumatic diseases other than rheumatoid arthritis. In this article we report on parasymphyseal insufficiency fractures in a patient with mixed connective tissue disease.

Multiple cerebellar infarction due to vertebral artery obstruction and bulbar symptoms associated with vertical subluxation and atlanto-occipital subluxation in ankylosing spondylitis.

Ankylosing spondylitis (AS) results in disease-specific inflammation at the site of ligamentous insertion into the bone. Atlantoaxial joint subluxation and vertical subluxation of the axis may occur as a consequence of instability resulting from the inflammatory process. Spontaneous anterior atlantoaxial subluxation is a well recognized complication in about 2% of patients with AS, and presents with or without signs of spinal cord compression. Vertical subluxation may follow anterior or posterior subluxation. It was noted in 3-8% of patients with rheumatoid arthritis, but is an exceedingly rare complication of AS. Moreover, it has never been reported that multiple cerebellar infarction and bulbar symptoms developed spontaneously due to atlanto-occipital subluxation and vertical subluxation in a patient with a long [corrected] history of AS. We describe a man with AS who developed multiple cerebellar infarction due to vertebral artery obstruction and bulbar symptoms associated with atlanto-occipital subluxation and vertical subluxation.

Adenosine-mediated photoreaction of 4,5',8-trimethylpsoralen with alcohols.

Irradiation of thin films consisting of 4,5',8-trimethylpsoralen (TMP), adenosine and small amounts of alcohols led to TMP-alcohol photoadducts in addition to TMP-adenosine photoadducts. Four TMP-ethanol and two TMP-methanol adducts have been separated and characterized. Covalent bonds were formed between the 4-carbon of TMP and the alpha-carbon to the hydroxy group in the alcohols. The TMP-alcohol photoadducts were formed only in the TMP film containing small amounts of alcohol and adenosine. Furthermore, no photoadduct of TMP and ribose was detected upon photolysis of a TMP-ribose film, suggesting that the adenine moiety plays a specific role in the reaction. The interaction of adenosine with psoralens in a dry film may be related to the DNA sequence selectivity observed for the photoreaction of psoralens with DNA.

Transient absorption spectra and quenching of coumarin excited states by nucleic acid bases.

Triplet-triplet absorption spectra of coumarin show different profiles and maxima in ethanol from those in water, which are very similar to those reported in benzene. Long-lived transient species other than triplet states were generated as initial photoproducts between coumarins and nucleic acid bases. The excited singlet and triplet states of coumarins were quenched by nucleic acid bases. Adenine base quenched the excited singlet state of coumarins more efficiently than thymine base. However, photocycloadducts of furocoumarins are formed predominantly with thymine, and not with adenine. Moreover, it is reported that the poly[dA-dT].poly[dA-dT] sequence region is the most favourable site for the photocycloaddition reaction of furocoumarins. The results imply that adenine contributes to singlet-state photocycloaddition reaction of furocoumarins with thymine, probably through an adenine-furocoumarin-thymine termolecular interaction.

A novel photoadduct of 4,5',8-trimethylpsoralen and adenosine.

A novel photoadduct of 4,5',8-trimethylpsoralen (TMP) and adenosine was isolated and purified by reverse-phase liquid chromatography. The structure of the photoproduct was determined by various spectral methods and found to be a TMP-adenosine 1:1 adduct resulting from the covalent bond formation between the carbon C(4) of TMP and ribose 4'-carbon of adenosine.

Study of the skin concentrations after administration of the various phototoxic drugs.

The skin concentrations of 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), and 4, 5', 8-trimethylpsoralen (TMP) were studied in the guinea pig following oral administration and bathing. The skin concentration of phototoxic drugs after oral administration peaked at 1.5 hours, and the concentration of 8-MOP was 3.5 times greater than that of 5-MOP. The skin concentration of TMP was not detected in our study (limit of sensitivity 5ng/ml). The skin concentrations of phototoxic drug after bathing decreased in the order of 5-MOP, TMP, and 8-MOP.

Photoreaction of 4,5',8-trimethylpsoralen with adenosine.

The near-UV induced photoreaction of 4,5',8-trimethylpsoralen (TMP) with adenosine was investigated in a dry film state. Four major photoadducts were isolated and purified by reverse-phase liquid chromatography. The structures of the photoproducts were elucidated on the basis of spectroscopic methods, including UV, FT-IR, mass spectrometry (FAB and EI methods) and 1H-NMR analysis. These photoproducts were characterized to be TMP-adenosine 1:1 adducts, which resulted from the covalent bond formation between the carbon C(4) of TMP and ribose 1' or 5' carbon of adenosine. Of the photoadducts, one photoadduct (V) was the major product, reflecting some selectivity in the photoreaction of TMP with adenosine in the solid state.

99Tcm-diastereomeric dimercaptosuccinic acid complexes: comparison of their biodistribution.

The biodistribution of two stereoisomeric 99Tcm complexes derived from diastereomeric dimercaptosuccinic acids (DMSA), 99Tcm-dl-DMSA and 99Tcm-meso-DMSA, was examined in sarcoma 180 tumour-bearing mice. The biodistribution pattern of meso-complex was not significantly different from 99Tc(V)m-DMSA, a new tumour imaging agent, while the dl-complex did not show the osteotropic property observed in meso- and 99Tc(V)m-DMSA complexes. The ratio of tumour to blood was superior for the 99Tcm-dl-DMSA (2.68) over the 99Tcm-meso-DMSA (1.25) at 3 h, and the ratio was reversed at 6 h, 3.13 to 4.28. The results indicate that dl-complex is of importance for the possible use in tumour imaging.

An efficient synthesis of 3 alpha-hydroxy-5 alpha-pregna-9(11),16-diene-20-one.

3 alpha-Hydroxy-5 alpha-pregna-9(11),16-diene-20-one (6) was synthesized for the first time from the commercially available 16,17 alpha-epoxy-3 beta-hydroxy-5-pregnen-20-one(1) in several steps. The key step involves a remote chlorination reaction utilizing m-iodobenzoate group as a free-radical guide.