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Biomedical subjects

Masato Mori

Publications and source records attributed to Masato Mori.

23 records · Page 2Linked to original sources

Liquid chromatographic determination of triethylenetetramine in human and rabbit sera based on intramolecular excimer-forming fluorescence derivatization.

A highly selective and simple fluorimetric liquid chromatographic method for the determination of triethylenetetramine (TETA), a therapeutic drug for Wilson's disease, in human and rabbit sera is described. This method is based on intramolecular excimer-forming fluorescence derivatization, which allows spectrofluorometric discrimination of polyamino compounds from monoamino species, followed by liquid chromatography. TETA and 1,6-hexanediamine (internal standard) were converted to the corresponding excimer-forming derivatives with a pyrene reagent, 4-(1-pyrene)butyric acid N-hydroxysuccinimide ester. The derivatives were separated within 20 min on a reversed-phase column using isocratic elution and detected spectofluorometrically at 480 nm with excitation at 345 nm. This method was successfully applied to the monitoring of TETA in human and rabbit sera with a simple pretreatment. The detection limit for TETA in serum was 18 ng/ml (0.13 nmol/ml) corresponding to 0.2 pmol on column at a signal-to-noise ratio of 3.

Adult↗

The human secretin gene: fine structure in 11p15.5 and sequence variation in patients with autism.

Secretin is a peptide hormone involved in digestion that has been studied as a potential therapeutic agent in patients with autism. We characterized the human secretin locus to determine whether mutations in this gene might play a role in a fraction of autism patients. While the secretin gene (SCT) was not found to be mutated in the majority of autistic patients, rare heterozygous sequence variants were identified in three patients. We also investigated length variation in a variable number of tandem repeats (VNTR) immediately upstream of SCT and found no significant differences in length between patients with autism and normal controls. SCT is located on 11p15.5, adjacent to DRD4 and HRAS. This region has been reported to be associated with both autism and attention deficit hyperactivity disorder (ADHD). Although imprinting is a characteristic of some genes in the vicinity, we could find no evidence for methylation of SCT in lymphoblast cells from patients or control individuals.

Amino Acid Sequence↗

Association of autism in two patients with hereditary multiple exostoses caused by novel deletion mutations of EXT1.

Two boys from separate families presented with hereditary multiple exostoses (EXT) and autism associated with mental retardation. Their fathers both expressed a clinical phenotype of hereditary multiple exostoses milder than those of the patients and without the associated mental disorder. The EXT1 and EXT2 genes from lymphocytes of the affected individuals were analyzed by using denaturing high-performance liquid chromatography and direct sequencing. A novel deletion mutation, 1742delTGT-G in exon 9 of EXT1, causing a frameshift was detected in one boy and his father. Another novel deletion mutation, 2093delTT in exon 11 of EXT1, causing transcription termination was detected in the other affected boy and his father. EXT1 is expressed in the brain, and both EXT1 and EXT2 proteins are associated with glycosyltransferase activities required for the biosynthesis of heparan sulfate, which also has activity in the brain. The coincidental association of mental disorders in the boys was not completely excluded. However, these results suggest the involvement of EXT1 in the development of mental disorders, including mental retardation and autism.

Autistic Disorder↗

Development of an enzyme-linked immunosorbent assay for the quantification of amiodarone.

A sensitive and specific enzyme-linked immunosorbent assay for an antiarrhythmic drug, amiodarone (AMI), was developed, which is capable of measuring levels as low as 16 ng/ml. Anti-AMI antibody was obtained by immunizing rabbits with an antigen conjugated with bovine serum albumin using diazotized 4-amino-1-(2-diethylaminoethoxy)-2,6-diiodobenzene. Enzyme labeling of AMI with beta-D-galactosidase was similarly performed using a diazotized 4-amino-1-(2-diethylaminoethoxy)-2,6-diiodobenzene. This enzyme-linked immunosorbent assay was specific for AMI and showed a very slight cross-reactivity (1.25%) with its major metabolite, mono-N-desethylamiodarone. The values of the AMI concentrations measured by this assay were in good correlation to those by HPLC. Its analytical applicability was demonstrated by a kinetic study with human liver microsomes. The enzyme-linked immunosorbent assay should be a valuable tool in therapeutic drug monitoring and pharmacokinetic studies of AMI.

Amiodarone↗