大腿骨骨転移に対する放射線治療後の骨折 : 発生率、発生時期、臨床像について

藤田保健衛生大

Causative Mechanism of Reflux Esophagitis induced by Digestive Secretions

Mechanisms producing reflux esophagitis were experimentally evaluated to clarify a direct action of digestive secretions to the esophageal mucosa. Mucosal lesions of reflux esophagitis were grossly composed of erosion, ulceration and loss of normal lustrous appearance. Based on histological examination, the degrees of erosion, ulceration and cell infiltraiton were also compared with respect to the severity of reflux esophagitis. Causative mechanisms of reflux esophagitis due to gastric juice alone are different from those due to another digestive secretions in relation to either the gastrectomized status or not

Comparative Study between the jejunum and Colon as Substitute for the Esophagus in Terms of Blood Flow

The advantages over a substitute for attaining the continuity following resection of the esophagus were experimentally compared between the jejunum and the colon in terms of changes in blood flow in the vascular pedicles under the influence of mechanical tension, induced systemic hypoxia and hypotension. Blood flow of the pedicled jejunal and colonic grafts used were measured with the use of direct collection through catheter introduced to the pedicled vessel. 1) As for tension-load added to the pedicle, the colon was much more tolerable rather than the jejunum. When a 40g tension was added to the jejunum, blood flow was remarkably reduced whereas there was no significant change in the colon even when a 100g tension was added. 2) As for the influence of induced hypoxic load, blood flow to the pedicled grafts was reduced when the arterial Po2 fell to below 70mg and Pco2 over 50mg. 3) As for the influence of induced systemic hypotensive load, it was significantly reduced to below about 30% of the normal systemic blood pressure in the similar patterns between the jejunum and the colon

Orthokeratinized Odontogenic Cyst of the Mandible with Heterotopic Cartilage

Cartilaginous metaplasia is a rare but well-documented phenomenon occurring in the wall of odontogenic keratocyst. The mural cartilage not associated with odontogenic keratocyst has been reported only once in a maxillary teratoid cyst of congenital origin to our knowledge. A case presented is a 38-year-old man with intraosseous keratinizing epidermoid cyst in the mandible, the wall of which contained a nodule of mature hyaline cartilage. The present lesion likely represents a previously undescribed, histologic hybrid consisting of orthokeratinized odontogenic cyst and cartilaginous heterotopia

IRIS plus panitumumab for metastatic CRC

Background Irinotecan plus S-1 (IRIS) is the only oral fluoropyrimidine-based regimen reported to be non-inferior to FOLFIRI and widely used in clinical practice for metastatic colorectal cancer (mCRC) patients. However, the combination of IRIS plus an anti-EGFR agent has not been evaluated previously. This study aimed to investigate the feasibility and efficacy of IRIS with panitumumab as second-line therapy for wild-type KRAS mCRC. Methods Main inclusion criteria were patients with wild-type KRAS mCRC refractory to one prior chemotherapy regimen for mCRC, ECOG PS 0-2, and age ≥ 20 years. Patients received panitumumab (6mg/kg) and irinotecan (100mg/m2) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was the feasibility of the therapy. The secondary endpoints were response rate (RR), progression-free survival (PFS), and overall survival (OS). Results A total of 36 patients received protocol treatment in eight centers. Of these, 23 patients (63.9%) completed protocol treatment, demonstrating achievement of the primary endpoint. The most frequent grade 3/4 toxicities were diarrhea (16.7%), acne-like rash (13.9%), and neutropenia (11.1%). The overall RR was 33.3% (12/36). Of these 4 five underwent conversion surgery. Median PFS and OS were 9.5 months (95% CI 3.5-15.4 months) and 20.1 months (95% CI 16.7-23.2 months), respectively. Conclusion IRIS plus panitumumab has an acceptable toxicity profile and a promising efficacy in patients with previously treated wild-type KRAS mCRC. Accordingly, this regimen can be an additional treatment option for second-line chemotherapy in wild-type KRAS mCRC

Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology

Somatic NLRP3 mosaicism in Muckle-Wells syndrome. A genetic mechanism shared by different phenotypes of cryopyrin-associated periodic syndromes

Familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS), and chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome are dominantly inherited autoinflammatory diseases associated to gain-of-function NLRP3 mutations and included in the cryopyrin-associated periodic syndromes (CAPS). A variable degree of somatic NLRP3 mosaicism has been detected in ≈35% of patients with CINCA. However, no data are currently available regarding the relevance of this mechanism in other CAPS phenotypes. OBJECTIVE: To evaluate somatic NLRP3 mosaicism as the disease-causing mechanism in patients with clinical CAPS phenotypes other than CINCA and NLRP3 mutation-negative. METHODS: NLRP3 analyses were performed by Sanger sequencing and by massively parallel sequencing. Apoptosis-associated Speck-like protein containing a CARD (ASC)-dependent nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB) activation and transfection-induced THP-1 cell death assays determined the functional consequences of the detected variants. RESULTS: A variable degree (5.5-34.9%) of somatic NLRP3 mosaicism was detected in 12.5% of enrolled patients, all of them with a MWS phenotype. Six different missense variants, three novel (p.D303A, p.K355T and p.L411F), were identified. Bioinformatics and functional analyses confirmed that they were disease-causing, gain-of-function NLRP3 mutations. All patients treated with anti-interleukin1 drugs showed long-lasting positive responses. CONCLUSIONS: We herein show somatic NLRP3 mosaicism underlying MWS, probably representing a shared genetic mechanism in CAPS not restricted to CINCA syndrome. The data here described allowed definitive diagnoses of these patients, which had serious implications for gaining access to anti-interleukin 1 treatments under legal indication and for genetic counselling. The detection of somatic mosaicism is difficult when using conventional methods. Potential candidates should benefit from the use of modern genetic tool