Phagocytosis of Advanced Glycation End Products (AGEs) in Macrophages Induces Cell Apoptosis

Advanced glycation end products (AGEs) are the products of a series of nonenzymatic modifications of proteins by reducing sugars. AGEs play a pivotal role in development of diabetic complications and atherosclerosis. Accumulation of AGEs in a vessel wall may contribute to the development of vascular lesions. Although AGEs have a diverse range of bioactivities, the clearance process of AGEs from the extracellular space, including the incorporation of AGEs into specific cells, subcellular localization, and the fate of AGEs, remains unclear. In the present study, we examined the kinetics of the uptake of AGEs by mouse macrophage J774.1 cells in vitro and characterized the process. We demonstrated that AGEs bound to the surface of the cells and were also incorporated into the cytoplasm. The temperature- and time-dependent uptake of AGEs was saturable with AGE concentration and was inhibited by cytochalasin D but not chlorpromazine. We also observed the granule-like appearance of AGE immunoreactivity in subcellular localizations in macrophages. Higher concentrations of AGEs induced intracellular ROS and 4-HNE, which were associated with activation of the NF-κB pathway and caspase-3. These results suggest that incorporation of AGEs occurred actively by endocytosis in macrophages, leading to apoptosis of these cells through NF-κB activation

The Japanese Society of Pathology Guidelines on the handling of pathological tissue samples for genomic research: Standard operating procedures based on empirical analyses

Genome research using appropriately collected pathological tissue samples is expected to yield breakthroughs in the development of biomarkers and identification of therapeutic targets for diseases such as cancers. In this connection, the Japanese Society of Pathology (JSP) has developed “The JSP Guidelines on the Handling of Pathological Tissue Samples for Genomic Research” based on an abundance of data from empirical analyses of tissue samples collected and stored under various conditions. Tissue samples should be collected from appropriate sites within surgically resected specimens, without disturbing the features on which pathological diagnosis is based, while avoiding bleeding or necrotic foci. They should be collected as soon as possible after resection: at the latest within about 3 h of storage at 4°C. Preferably, snap‐frozen samples should be stored in liquid nitrogen (about −180°C) until use. When intending to use genomic DNA extracted from formalin‐fixed paraffin‐embedded tissue, 10% neutral buffered formalin should be used. Insufficient fixation and overfixation must both be avoided. We hope that pathologists, clinicians, clinical laboratory technicians and biobank operators will come to master the handling of pathological tissue samples based on the standard operating procedures in these Guidelines to yield results that will assist in the realization of genomic medicine

Absence of the Sternocleidomastoid Muscle in a Patient That Underwent Neck Dissection for Squamous Cell Carcinoma of the Tongue

The congenital absence of a skeletal muscle is a rare cause of congenital muscular torticollis, and the condition is associated with various unusual anatomical structures. We describe a rare case of congenital absence of the sternocleidomastoid muscle associated with squamous cell carcinoma of the tongue in a patient who underwent neck dissection. In this case, both the external jugular vein and the spinal accessory nerve were absent. However, we found that branches of the C3 nerve extended from the cervical plexus to the trapezius muscle and seemed to be acting as trapezius muscle motor nerves in place of the accessory nerve. After the operation, the patient was able to lift and abduct his right arm, and his shoulder did not droop

Metastasis to the Lingual Lymph Node in Patients with Squamous Cell Carcinoma of the Floor of the Mouth:A Report of Two Cases

Cancer of the tongue or the floor of the mouth sometimes metastasizes to the lingual lymph node. We present two patients with squamous cell carcinoma of the floor of the mouth who developed metastases to the lateral lingual lymph nodes. Case 1, a 62-year old male, had squamous cell carcinoma of the floor of the mouth (T3N2cM0). He underwent tumor resection and bilateral neck dissection, and histological examination revealed five metastatic nodes including the lateral lingual node near the hyoid bone. No recurrent tumors were evident, but he died of pneumonia 10 months after the surgery. Case 2, a 62-year old male, had squamous cell carcinoma of the floor of the mouth (T2N2cM0). He underwent tumor resection and bilateral neck dissection, and histological examination revealed three metastatic nodes including the lateral lingual node near the sublingual gland. No recurrence was found in the oral and neck regions, but he died of liver metastasis 18 months after the surgery. Metastasis to the lingual lymph node may cause a recurrence of oral cancer in the neck, since conventional neck dissection cannot remove this node even in the case of enbloc resection of the primary tumor and the neck. When CT, MRI, or intra-operative palpation findings lead to a suspicion of metastasis to the lingual lymph node, the area of neck dissection should be extended to include this node

Geological background of the Kairei and Edmond hydrothermal fields along the Central Indian Ridge : Implications for the distinct chemistry between their vent fluids

Hydrogen-rich hydrothermal areas, such as those in the Indian Ocean, may have had an influence on early evolution of life on Earth and thus have attracted interest because they may be a proxy for ancient ecosystems. The Kairei and Edmond hydrothermal fields in the Indian Ocean are separated by 160 km, but exhibit distinct fluid chemistry: Kairei fluids are hydrogen-rich; Edmond fluids are hydrogen-poor. At this region, the Central Indian Ridge shows an intermediate spreading rate, 48 mm year−1 as full rate, where the hydrothemal fields occur. Kairei field vent fluids show persistently high concentrations of H2. The Kairei field seems to be unique among hydrogen-enriched hydrothermal regions: most similar hydrogen-rich hydrothermal activity occurs along slowly spreading ridge, <40 mm year−1. The geological and tectonic aspects of the Kairei and Edmond hydrothermal fields were studied to try to elucidate geological constraints on hydrogen production. Visual observations of the seafloor near Kairei from a submersible revealed olivine-rich plutonic rocks with olivine gabbro-troctolite-dunite assemblages exposed within 15 km of the vent field, with serpentinized ultramafic mantle rocks on the Oceanic Core Complex (OCC). The OCC area might be a recharge zone of Kairei hydrothermal activity producing H2-rich vent fluids. The chaotic seafloor within 30 km of the Kairei field reflects a magma-starved condition persisting there for 1 Myr. Asymmetric geomagnetic and gravity anomalies near the Kairei field can be used to infer that patchy olivine-rich intrusions are scattered within mantle ultramafics, where infiltrated seawater reacts with magma and ultramafic rocks or olivine-rich rocks. The heterogeneous uppermost lithosphere containing shallow olivine-rich rock facies surrounding the Kairei field provides abundant H2 into the vent fluid through serpentinization. The hydrogen-rich Kairei field is hosted by basalt, with mafic-ultramafic olivine-rich lithology; the ordinary, hydrogen-poor Edmond field is hosted by a normal basaltic lithology. The contrasting geochemical signatures of the two fields reported here can also be found in ancient rocks from a juvenile Earth. This suggests that lithology-controlled generation of hydrogen may have operated for a long time and be relevant to the origin of life on Earth