定量的磁化率マッピングを用いた歯状核におけるガドリニウム沈着の定量的検討

京都大学0048新制・課程博士博士(医学)甲第20973号医博第4319号新制||医||1026(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 溝脇 尚志, 教授 村井 俊哉, 教授 鈴木 実学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

A Polymerase-chain-reaction Assay for the Specific Identification of Transcripts Encoded by Individual Carcinoembryonic Antigen (CEA)-gene-family Members

Carcinoembryonic antigen (CEA) is a tumor marker that belongs to a family of closely related molecules with variable expression patterns. We have developed sets of oligonucleotide primers for the specific amplification of transcripts from individual CEA-family members using the reverse transcriptase/ polymerase chain reaction (RT/PCR). Specific primer sets were designed for CEA, non-specific cross-reacting antigen (NCA), biliary glycoprotein (BGP), carcinoembryonic antigen gene-family members 1, 6 and 7 (CGMI, CGM6 and CGM7), and one set for all pregnancy-specific glycoprotein (PSG) transcripts. Primers were first tested for their specificity against individual cDNA clones and product-hybridization with internal, transcript-specific oligonucleotides. Total RNA from 12 brain and 63 gynecological tumors were then tested for expression of CEA-related transcripts. None were found in tumors located in the brain, including various mesenchymal and neuro-epithelial tumors. CEA and NCA transcripts were, however, present in an adenocarcinoma located in the nasal sinuses. In ovarian mucinous adenocarcinomas, we always found co-expression of CEA and NCA transcripts, and occasionally BGP mRNA. CEA-related transcripts were also found in some serous, endometrioid and clear-cell ovarian carcinomas. CEA, NCA and BGP transcripts were present in endometrial carcinomas of the uterus and cervical carcinomas, whereas uterine leiomyomas were completely negative. No transcripts were found from CGM 1, CGM6, CGM7 or from PSG genes in any of the tumors tested. The PCR data were compared with immunohistochemical investigations of ovarian tumors at the protein level using CEA (26/3/13)-, NCA-50/90 (9A6FR) and NCA-95 (80H3)-specific monoclonal antibodies

Analysis of the Size of the Carcinoembryonic Antigen (CEA) Gene Family

Five members of the human CEA gene family [human pregnancy-specific β1-glycoprotein (PSβG), hsCGM1, 2, 3 and 4] have been isolated and identified through sequencing the exons containing their N-terminal domains. Sequence comparisons with published data for CEA and related molecules reveal the existence of highly-conserved gene subgroups within the CEA family. Together with published data eleven CEA family members have so far been determined. Apart from the highly conserved coding sequences, these genes also show strong sequence conservation in their introns, indicating a duplication of whole gene units during the evolution of the CEA gene family

Long-Range Chromosomal Mapping of the Carcinoembryonic Antigen (CEA) Gene Family Cluster

A long-range physical map of the carcinoembryonic antigen (CEA) gene family cluster, which is located on the long arm of chromosome 19, has been constructed. This was achieved by hybridization analysis of large DNA fragments separated by pulse-field gel electrophoresis and of DNA from human/rodent somatic cell hybrids, as well as the assembly of ordered sets of cosmids for this gene region into contigs. The different approaches yielded very similar results and indicate that the entire gene family is contained within a region located at position 19q13.1–q13.2 between the CYP2A and the D19S15/D19S8 markers. The physical linkage of nine genes belonging to the CEA subgroup and their location with respect to the pregnancy-specific glycoprotein (PSG) subgroup genes have been determined, and the latter are located closer to the telomere. From large groups of ordered cosmid clones, the identity of all known CEA subgroup genes has been confirmed either by hybridization using gene-specific probes or by DNA sequencing. These studies have identified a new member of the CEA subgroup (CGM8), which probably represents a pseudogene due to the existence of two stop codons, one in the leader and one in the N-terminal domain exons. The gene order and orientation, which were determined by hybridization with probes from the 5′ and 3′ regions of the genes, are as follows: cen/3′-CGM7-5′/3′-CGM2-5′/5′-CEA-3′/5′-NCA-3′/5′- CGM1-3′/3′-BGP-5′/3′-CGM9-5′/3′-CGM6-5′/5′-CGM8-3′/PSGcluster/qter

The Human Pregnancy-Specific Glycoprotein Genes are Tightly Linked on the Long Arm of Chromosome 19 and are Coordinately Expressed

The pregnancy-specific glycoprotein (PSG) genes encode a group of proteins which are found in large amounts in placenta and maternal serum. In situ hybridization analyses of metaphase chromosomes reveal that all the human pregnancy-specific glycoprotein (PSG) genes are located on the long arm of chromosome 19 (19q13.2–13.3), overlapping the region containing the closely-related carcinoembryonic antigen (CEA) gene subgroup. Higher resolution analyses indicate that the PSG genes are closely linked within an 800kb SacII restriction endonuclease fragment. This has been confirmed through restriction endonuclease mapping and DNA sequence analyses of isolated genomic clones, which show that at least some of these genes are located in very close proximity. Further, these studies have helped to identify a new member of the PSG gene sub-family (PSG7). DNA/RNA hybridization analyses, using gene-specific oligonucleotide probes based on published sequences, showed that five from six PSG genes tested are coordinately transcribed in the placenta. Due to the close proximity of these genes and their coordinated expression pattern, common transcriptional regulatory elements may exist

Quantitative and qualitative evaluation of sequential PET/MRI using a newly developed mobile PET system for brain imaging

[Purpose]To evaluate the clinical feasibility of a newly developed mobile PET system with MR-compatibility (flexible PET; fxPET), compared with conventional PET (cPET)/CT for brain imaging.[Methods]Twenty-one patients underwent cPET/CT with subsequent fxPET/MRI using 18F-FDG. As qualitative evaluation, we visually rated image quality of MR and PET images using a four-point scoring system. We evaluated overall image quality for MR, while we evaluated overall image quality, sharpness and lesion contrast. As quantitative evaluation, we compared registration accuracy between two modalities [(fxPET and MRI) and (cPET and CT)] measuring spatial coordinates. We also examined the accuracy of regional 18F-FDG uptake.[Results]All acquired images were of diagnostic quality and the number of detected lesions did not differ significantly between fxPET/MR and cPET/CT. Mean misregistration was significantly larger with fxPET/MRI than with cPET/CT. SUVmax and SUVmean for fxPET and cPET showed high correlations in the lesions (R = 0.84, 0.79; P < 0.001, P = 0.002, respectively). In normal structures, we also showed high correlations of SUVmax (R = 0.85, 0.87; P < 0.001, P < 0.001, respectively) and SUVmean (R = 0.83, 0.87; P < 0.001, P < 0.001, respectively) in bilateral caudate nuclei and a moderate correlation of SUVmax (R = 0.65) and SUVmean (R = 0.63) in vermis.[Conclusions]The fxPET/MRI system showed image quality within the diagnostic range, registration accuracy below 3 mm and regional 18F-FDG uptake highly correlated with that of cPET/CT

Comparison of TGSE-BLADE DWI, RESOLVE DWI, and SS-EPI DWI in healthy volunteers and patients after cerebral aneurysm clipping

Diffusion-weighted magnetic resonance imaging is prone to have susceptibility artifacts in an inhomogeneous magnetic field. We compared distortion and artifacts among three diffusion acquisition techniques (single-shot echo-planar imaging [SS-EPI DWI], readout-segmented EPI [RESOLVE DWI], and 2D turbo gradient- and spin-echo diffusion-weighted imaging with non-Cartesian BLADE trajectory [TGSE-BLADE DWI]) in healthy volunteers and in patients with a cerebral aneurysm clip. Seventeen healthy volunteers and 20 patients who had undergone surgical cerebral aneurysm clipping were prospectively enrolled. SS-EPI DWI, RESOLVE DWI, and TGSE-BLADE DWI of the brain were performed using 3 T scanners. Distortion was the least in TGSE-BLADE DWI, and lower in RESOLVE DWI than SS-EPI DWI near air–bone interfaces in healthy volunteers (P < 0.001). Length of clip-induced artifact and distortion near the metal clip were the least in TGSE-BLADE DWI, and lower in RESOLVE DWI than SS-EPI DWI (P < 0.01). Image quality scores for geometric distortion, susceptibility artifacts, and overall image quality in both healthy volunteers and patients were the best in TGSE-BLADE DWI, and better in RESOLVE DWI than SS-EPI DWI (P < 0.001). Among the three DWI sequences, image quality was the best in TGSE-BLADE DWI in terms of distortion and artifacts, in both healthy volunteers and patients with an aneurysm clip