[A Case of Locally Advanced Unresectable Esophageal Cancer Treated with Nivolumab and Ipilimumab Therapy Followed by Surgery].

In cases of unresectable, locally advanced esophageal cancer, conversion surgery may be considered if chemotherapy produces favorable results and surgical resection is indicated. The use of immune checkpoint inhibitors in chemotherapy for esophageal cancer has expanded, and has increased the number of cases in which conversion surgery becomes possible. The patient in the present report had received a diagnosis of Stage Ⅳa esophageal carcinoma, and a prior nephroureterectomy discouraged the administration of platinum-based agents. Nivolumab and ipilimumab were administered as induction chemotherapy. Despite the achievement of stable disease, the patient's esophageal stricture deteriorated, necessitating surgical intervention. The resected specimen revealed that fewer than 50% of malignant cells remained viable and residual cancer cells were noticeably absent, particularly in the enlarged lymph nodes. We herein present the details of this case and discuss the literature concerning surgery following immune checkpoint inhibitor therapy.

Fracture origin and crack propagation of CAD/CAM composite crowns by combining of in vitro and in silico approaches.

PURPOSE: Fractographic analysis has been used to investigate the fracture behavior of Computer-aided design/computer-aided manufacturing (CAD/CAM) composite crowns by subjecting them to compression tests. However, it is difficult to investigate details of the fracture, including its initiation and propagation, using in vitro tests. The aim of this study was to determine the fracture origins and the order of crack initiation of CAD/CAM composite crowns using in silico nonlinear dynamic finite element analysis (FEA). MATERIAL AND METHODS: The following materials were used: Cerasmart (CS), Katana Avencia Block (KA), and Shofu Block HC (HC) as CAD/CAM crowns, Panavia SA Cement Plus (SA) as a luting material, and Clearfil DC Core Plus (DC) as an abutment. The elastic moduli and fracture strain of each material were obtained from the stress-strain curve of in vitro three-point bending tests. The fracture origins and order of crack initiation of the materials were determined by in silico nonlinear dynamic compression analysis. Load-displacement curves were statistically compared with the results of the in vitro compression tests (Pearson's correlation test, α = 0.05). RESULTS: The nonlinear dynamic FEA demonstrated that crack initiation was primarily observed near the lingual side of the CAD/CAM crowns and immediately propagated to the central fossa. The models were fractured following the in vitro fracture strains, showing the same order for the products tested (CS/KA/HC, SA, and DC). Load-displacement curves with the use of CS, KA, and HC were significantly correlated to the corresponding in vitro compression tests results (CS: r = 0.985, p < 0.05, KA: r = 0.987, p < 0.05, and HC: r = 0.997, p < 0.05). CONCLUSIONS: The in silico model established in this study clarified the crack initiation of the CAD/CAM composite crowns and the order of crack initiation among the investigated products, suggesting that the present approach is useful for analyzing the fracture behavior of CAD/CAM composite crowns in detail.

Analysis of ABCC6 (MRP6) in normal human tissues.

To determine the tissue distribution of the ABC transporter ABCC6 in normal human tissues, we analyzed tissue arrays for the presence of ABCC6 mRNA by in situ hybridization and ABCC6 protein by immunohistochemistry using the polyclonal antibody HB-6. We detected ABCC6 mRNA and protein in various epithelial cells of exocrine and endocrine tissues, such as acinar cells in the pancreas, mucosal cells of the intestine and follicular epithelial cells of the thyroid. We obtained a very strong immunostaining for enteroendocrine G cells in the stomach. In addition, ABCC6 mRNA and protein were present in most neurons of the brain, in alveolar macrophages in the lungs and lymphocytes in the lymph node. Immunohistochemisty using the monoclonal antibody M6II-31 confirmed the widespread tissue distribution of ABCC6. The physiological substrate(s) of ABCC6 are yet unknown, but we suggest that ABCC6 fulfills multiple functions in different tissues. The strong immunostaining for ABCC6 in G cells suggests that it plays an important role in these endocrine cells.

Comparative immunocytochemical localization of lysyl oxidase (LOX) and the lysyl oxidase-like (LOXL) proteins: changes in the expression of LOXL during development and growth of mouse tissues.

Lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) are extracellular enzymes that deaminate peptidyl lysyl residues involved in the cross-linking of fibrillar collagens and elastin. While LOX is required for the survival of newborn mice, the role of LOXL during development remains unclear. Studies have shown that the same cell types express LOX and LOXL in the same tissues, but no functional differences have been established. We have compared the immunohistochemical localization of LOX and LOXL in various tissues from normal, young adult mice. LOX and LOXL were co-localized in the skin, aorta, heart, lung, liver and cartilage, but were localized to different areas in the kidney, stomach, small intestine, colon, retina, ovary, testis and brain. LOXL expression was further examined in tissues from different developmental stages. In embryonic mice (10.5-14.5 dpc), LOXL immunostaining was abundant in the heart, liver, intestine, and neural tube. LOXL was present in most major organs in late fetal (16.5 dpc) and newborn mice, but generally diminished as animals aged. Immunoreactivity was significantly reduced in the heart, lung, kidney and liver of 2 year-old mice, but remained prevalent in the skin and tongue. LOX and LOXL were also found in the nuclei of cells in a number of tissues. These results indicate that LOXL has a role during mouse development and in the maintenance of adult tissues.

Progressive hair loss and myocardial degeneration in rough coat mice: reduced lysyl oxidase-like (LOXL) in the skin and heart.

The rough coat (rc) is a spontaneous recessive mutation in mice. To identify the mutated gene, we have characterized the rc phenotype and initiated linkage mapping. The rc mice show growth retardation, cyclic and progressive hair loss, hyperplastic epidermis, abnormal hair follicles, cardiac muscle degeneration, and reduced amount of collagen and elastin in the skin and heart. The rc locus was mapped at 32.0 cM on chromosome 9, close to the loxl gene. Lysyl oxidase-like (LOXL) protein is a novel copper-containing amine oxidase that is required for the cross-linking of elastin and collagen in vitro. LOXL is expressed at high levels in the skin and heart, where the rc mice show strong phenotype. The expression pattern and the genetic proximity to rc suggested loxl as a potential candidate gene. In rc mice, the loxl mRNA was reduced in the skin and the LOXL protein in the heart, dermis, atrophic hair follicles, and sebaceous glands. No mutations, however, were identified within the coding region of loxl, and offspring from rc/rc and loxl null mice crossing were phenotypically normal. Based on these results, loxl appears non-allelic to rc. Heart- and skin-specific downregulation of LOXL in rc mice, however, may contribute to the extracellular matrix alterations and the rc phenotype.

The distribution of Abcc6 in normal mouse tissues suggests multiple functions for this ABC transporter.

We have studied the tissue distribution of Abcc6, a member of the ABC transmembrane transporter subfamily C, in normal C57BL/6 mice. RNase protection assays revealed that although almost all tissues studied contained detectable levels of the mRNA encoding Abcc6, the highest levels of Abcc6 mRNA were found in the liver. In situ hybridization (ISH) demonstrated abundant Abcc6 mRNA in epithelial cells from a variety of tissues, including hepatic parenchymal cells, bile duct epithelia, kidney proximal tubules, mucosa and gland cells of the stomach, intestine, and colon, squamous epithelium of the tongue, corneal epithelium of the eye, keratinocytes of the skin, and tracheal and bronchial epithelium. Furthermore, we detected Abcc6 mRNA in arterial endothelial cells, smooth muscle cells of the aorta and myocardium, in circulating leukocytes, lymphocytes in the thymus and lymph nodes, and in neurons of the brain, spinal cord, and the specialized neurons of the retina. Immunohistochemical analysis using a polyclonal Abcc6 rabbit antibody confirmed the tissue distribution of Abcc6 suggested by our ISH studies and revealed the cellular localization of Abcc6 in the basolateral plasma membrane in the epithelial cells of proximal convoluted tubules in the kidney. Although the function of Abcc6 is unknown, mutations in the human ABCC6 gene result in a heritable disorder of connective tissue called pseudoxanthoma elasticum (PXE). Our results demonstrating the presence of Abcc6 in epithelial and endothelial cells in a variety of tissues, including those tissues affected in PXE patients, suggest a possible role for Abcc6 in the normal assembly of extracellular matrix components. However, the presence of Abcc6 in neurons and leukocytes, two cell populations not associated with connective tissue, also suggests a more complex multifunctional role for Abcc6.

Self-esteem and mental health characteristics especially among lean students surveyed by University Personality Inventory.

In recent years, various investigators have indicated an increase in the number of eating disorders. A similar tendency has been observed among university students. The purpose of the present study is to clarify the self-esteem and mental health characteristics of the lean students who suffer from latent eating disorders. We examined 2132 responses to the University Personality Inventory obtained from students who entered Nagoya University in 1995. We analyzed the mental health conditions of the lean students after categorizing the subjects into lean, normal and obese group by body mass index. As a result, the following results were obtained. Lean male students presented with more subjective symptoms than normal and obese students, and extremely lean male students had more subjective symptoms. Lean female students had fewer subjective symptoms than lean male students and no particular differences from normal female students. It is suggested that male and female students had different criteria for self-esteem with regard to body shape. The lean female students were medically ill and formed a latent or borderline latent group with anorexia nervosa. However, they had a similar degree of health awareness as normal students.

Associations between physical strength, cerebral function and mental health in independent-living elderly Japanese women.

OBJECTIVES: To evaluate the physical strength, cerebral function, and mental health conditions in elderly persons, and to examine the correlation between these functions. METHODS: The subjects were 151 independent-living elderly Japanese women, mean age 70 +/-5 years (+/-SD; range, 60 to 80 years), with normal abilities in daily life. The health check-up was conducted from April to May 1997. Physical strength was estimated by measuring seven activities. Cerebral functions were assessed by six sub-tests of the General Aptitude Test Battery (GATB). Their mental health status was measured by four sub-scales of the General Health Questionnaire (GHQ)-28. RESULTS: The physical strenght and almost all of the cerebral functions decreased with age. Social dysfunction and severe depression on the GHQ sub-scales also worsened with age. Physical strength was strongly correlated with cerebral functions after adjusting for the confounding effect of aging. There were also interrelations between physical strength and mental health. CONCLUSIONS: This study provided important information on the correlation between physical and mental status in elderly women. Future longitudinal studies with the intervention of physical training are required to determine whether a causal relationship exists between these factors.