Yoshito Irizawa

Human orosomucoid polymorphism : molecular basis of the three common ORM1 alleles, ORM1*F1, ORM1*F2, and ORM1*S

Abstract The human orosomucoid (ORM) is controlled by two closely linked loci, ORM1 and ORM2, and two tandem genes, AGP1 and AGP2, encoding the proteins produced by the two loci, have been cloned. In this study the molecular basis of ORM1 polymorphism was investigated. For the detection of mutations the products of the six exons of each gene, amplified by the polymerase chain reaction (PCR), were screened by single-strand conformation polymorphism analysis. Subsequently, the exons with an altered migration pattern were gene-specifically amplified by nested PCR. Sequencing of the gene-specific PCR products showed that the three common ORM1 alleles result from A→G transitions at the codons for amino acid positions 20 in exon 1 and 156 in exon 5 of the AGP1 gene: ORM1*F1 was characterized by CAG (Gln) and GTG (Val), ORM1*F2, by CAG (Gln) and ATG (Met), and ORM1*S, by CGG (Arg) and GTG (Val). The phylogenesis of the genes encoding these three ORM1 alleles is discussed.

Assessment of dementia in patients with multiple system atrophy.

Background and purpose:  We investigated dementia in patients with multiple system atrophy (MSA) in order to characterize the prevalence and nature of impairments in these patients.

MATP polymorphisms in Germans and Japanese: the L374F mutation as a population marker for Caucasoids

Inference of the population and ancestry to which an individual belongs is important in forensic individualization and personal identification. In this study, five polymorphisms of the membrane-associated transporter protein (MATP) gene were investigated in German and Japanese populations. The L374F mutation was present at an allele frequency as high as 0.96 in the German population, whereas it was completely absent in the Japanese population. This extreme difference in allele frequency suggests that the L374F mutation is valuable as a population and ancestry informative marker for Caucasoids.

Association of visual hallucinations with reduction of MIBG cardiac uptake in Parkinson's disease.

BACKGROUND Postganglionic cardiac sympathetic denervation is evident in patients with Parkinsons disease (PD) and iodine-123 metaiodobenzylguanidine ((123)I-MIBG) cardiac scintigraphy has proven to be a useful tool for diagnosis of PD. OBJECTIVE To elucidate the factors associated with severity of cardiac sympathetic nerve dysfunction in PD patients. METHODS We investigated 95 PD patients hospitalized in the Department of Neurology at Tottori University Hospital. (123)I-MIBG cardiac scintigraphy was performed on each patient and the early and delayed heart to mediastinum (H/M) ratios and washout rate (WR) of (123)I-MIBG cardiac scintigraphy were calculated. Independent predictive variables for parameters of (123)I-MIBG cardiac scintigraphy were analyzed by multivariate regression analysis. RESULTS Multivariate regression analysis revealed that the presence of visual hallucinations (VH) and the patients age at the time of evaluation independently predicted the early or delayed H/M ratio. Analysis of covariance, adjusted for the age of the patients as covariates, revealed that the early and delayed H/M ratios of PD patients with VH but no dementia, as well as PD patients with dementia were significantly lower than the ratios in PD patients with no VH or dementia. CONCLUSION Cardiac sympathetic dysfunction may be associated with the presence of VH in PD patients.

Clinical evaluation of Parkinson’s disease dementia: association with aging and visual hallucination

Objectives –  In order to explore factors associated with the development of dementia in Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB), we systematically investigated the clinical evaluation of PD and DLB patients hospitalized in the Department of Neurology at Tottori University Hospital, Japan.

The human complement component C1R gene: the exon-intron structure and the molecular basis of allelic diversity.

Human C1r is a component of the complement system, which is a major mediator of innate immunity. In this study we investigated the exon‐intron organization of the human C1R gene, which spans 11 kb from the initiation codon to the stop codon, and is very similar in exon‐intron structure to the C1S gene. Six common and rare alleles, C1R*1, C1R*2, C1R*5, C1R*8, C1R*9, and C1R*13, were characterized by five mutations at amino acid positions 114, 135, 146, 167 and 244, in exons 4, 5 and 7 where the CUB1, EGF and CUB2 domains are encoded, respectively. A comparison with the cDNA of the mouse C1r gene showed that C1R*2is likely to be an ancestral allele. In addition, nine nucleotide substitutions and one length polymorphism were found in introns 2, 3, 4, 8 and 10.

Development of an instrument to measure postmortem lividity and its preliminary application to estimate the time since death

A degree of postmortem lividity was related to a subcutaneous hemoglobin concentration, which can be measured by using light absorption. On the basis of this theory, the authors have developed an instrument utilizing a light to measure the degree of postmortem lividity. By using 42 corpses whose postmortem intervals were known, the authors examined the relationship between the actual postmortem intervals and the measurements, and found that there was significant correlation between them.

Characterization of genomic rearrangements of the α1-acid glycoprotein/orosomucoid gene in Ghanaians

AbstractIn this study, the structure of the α1-acid glycoprotein (AGP), or orosomucoid (ORM), gene was investigated in a Ghanaian mother and her child, who shared an unusual variant, ORM1 S2(C), found by isoelectric focusing. Three remarkable changes of nucleotide sequence were observed: (1) The two ORM1 alleles, ORM1*S and ORM1*S2(C), had the AGP2 gene-specific sequence at one and three regions, respectively, in exon 5 to intron 5. The variant allele originating from ORM1*S was characterized by a G-to-A transition, resulting in an amino acid change from valine to methionine, which is also detected in ORM1 F2, a form that is common in Europeans. (2) The AGP2 gene of the child, inherited from the father, was duplicated, as revealed by long-range polymerase chain reaction. (3) Three new mutations were observed in two exons of the AGP2 genes of the mother and child. All of these novel genomic rearrangements, which were not observed in Japanese subjects, may have arisen through point mutation, gene conversion, and unequal crossover events. It is likely that the rearrangement of the AGP gene has often occurred in Africans.

A hypervariable STR polymorphism in the complement factor I (CFI) gene: Asian-specific alleles.

In this study, a short tandem repeat (STR) polymorphism in intron 7 of the human complement factor I (CFI) gene was studied in 637 DNA samples obtained from African, German, Thai, and Japanese populations and German and Japanese families. A total of 41 alleles were observed and classified into two groups, L and H, based on size differences. Group H, which consisted of 16 alleles, was observed only in Thai and Japanese populations at frequencies of 0.162 and 0.116, respectively, and was strongly associated with c.1217A in exon 11 (CFI*Ah). The heterozygosity values ranged from 0.89 in German to 0.93 in Thai populations. This STR would be a useful supplementary marker for forensic individualization.

Effects of weight bearing on the tidemark and osteochondral junction of articular cartilage: Histomorphometric analyses of 7 normal femoral heads

To study the effect of weight bearing on the tidemark and osteochondral junction, we compared the morphology of these two boundaries in weight-bearing and less weight-bearing regions of normal human femoral heads. We measured the irregularities of the boundaries in the two regions using an X-Y digitizer connected to a computer in histological whole sections of femoral heads in 7 subjects without joint diseases. The irregularity of the tidemark was small, showing no difference between the two regions. However, the irregularity of the osteochondral junction in the weight-bearing region was greater than in the less weight-bearing region, which was confirmed by three-dimensional reconstructed images. Our findings suggest that mechanical stresses greatly influence the morphology of the osteochondral junction compared to the influence of such stresses on the tidemark, and that the marked irregularity of the osteochondral junction in the weight-bearing region is a reactive phenomenon against mechanical fragility due to simple contact between calcified cartilage and subchondral bone without fibrous connections.