An improvement in photodynamic therapy (PDT) efficiency against a human gastric cancer cell line (MKN45) with 5-aminolevulinic acid (ALA) and lanthanide nanoparticles (LNPs) is described. An ...endogenous photosensitizer, protoporphyrin IX, biosynthesized from ALA and selectively accumulated in cancer cells, is sensitizable by the visible lights emitted from up-conversion LNPs, which can be excited by a near-infrared light. Ten kinds of surface modifications were performed on LNPs, NaYF₄(Sc/Yb/Er) and NaYF₄(Yb/Tm), in an aim to distribute these irradiation light sources near cancer cells. Among these LNPs, only the amino-functionalized LNPs showed affinity to MKN45 and HeLa cancer cells. A PDT assay with MKN45 demonstrated that amino-modified NaYF₄(Sc/Yb/Er) gave rise to a dramatically enhanced PDT effect, reaching almost perfect lethality, whereas NaYF₄(Yb/Tm)-based systems caused little improvement in PDT efficiency. The improvement of PDT effect with the amino-modified NaYF₄(Sc/Yb/Er) is promising for a practical PDT against deep cancer cells that are reachable only by near-infrared lights.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Anaplastic lymphoma kinase (ALK)-positive histiocytosis is a rare emerging entity characterized by systemic or localized proliferation of histiocytes harboring ALK rearrangements. Breasts are ...reportedly affected by ALK-positive histiocytosis. Here, we evaluated 2 localized cases of breast ALK-positive histiocytosis through a comprehensive clinicopathologic, molecular, and genomic analysis to further delineate this entity and better understand its pathogenesis. The cases involved 2 undiagnosed ALK-positive spindle-cell breast lesions. Both cases were Asian women aged 30s to 40s who underwent excisions for asymptomatic breast masses. Macroscopically, both lesions were well-circumscribed, solid masses. Microscopically, both lesions were predominantly composed of fascicles with uniform, bland spindle cells, admixed with epithelioid histiocyte-like cells and lymphoid aggregates. Immunohistochemically, the spindle and epithelioid cells coexpressed ALK and histiocytic markers (eg, CD68, CD163). Genetically, both lesions harbored KIF5B-ALK, confirmed by fluorescence in situ hybridization and polymerase chain reaction-direct sequencing analyses. Combining these results, both cases were successfully diagnosed as ALK-positive histiocytosis. Furthermore, no common or previously annotated somatic alterations were identified by whole-exome sequencing. One case harbored clonal immunoglobulin gene rearrangements according to the polymerase chain reaction-based BIOMED-2 protocol. Therefore, ALK-positive histiocytosis can be accurately diagnosed through a combination of morphologic, immunohistochemical, and molecular analyses. In this entity, breast cases may have distinct clinicopathologic features: Asian women aged 30s to 40s, asymptomatic masses, and predominant spindled morphology. For pathogenesis, ALK rearrangements could be the driver alteration, and a subset of ALK-positive histiocytosis may harbor a lymphoid lineage. These findings can be utilized to improve the diagnosis of ALK-positive histiocytosis and better understand its pathogenesis.
Pulmonary embolism (PE) from deep venous thrombosis (DVT) can be a fatal postoperative complication. Preventive measures for venous thromboembolism (VTE) was evaluated in this hospital.
Preoperative ...DVT screening following surgery under general anesthesia in 2009–2016 was examined, and then, 217 patients diagnosed with DVT by preoperative leg-ultrasound (US) between 2014 and 2016 were retrospectively analyzed.
There were 24,826 operations under general anesthesia in the study period. Preoperative leg-US was performed in 5345 (21.5%) patients, and 648 (12.1% of patients, 2.6% of total operations) were diagnosed with DVT. In 2014–2016, 217 patients, which is 11.7% of patients undergoing leg-US, were diagnosed with DVT. DVT was found in the proximal veins (upper popliteal vein) in 86 (39.6%) patients. A total of 143 (62%) patients were considered to have organized thrombi, no patient developed pulmonary embolism, and 133 (58%) patients were discharged without follow-up examination for DVT. Ninety-six patients were evaluated for changes on leg-US, with no difference in the results with and without anticoagulant use. On multivariate logistic regression analysis, anticoagulants appeared effective for non-organized thrombi, higher D-dimer levels (≥10 μg/mL), or orthopedic surgery.
Preoperative screening for DVT did not appear useful, and treatment of asymptomatic DVT was not always necessary.
•Preoperative screening of leg-ultrasound diagnosed 12% of patients with DVT.•Developing symptomatic embolism was not associated with anticoagulant use.•Anticoagulants were effective for non-organized thrombi, higher D-dimer levels, or orthopedic surgery.•Preoperative screening for DVT did not appear useful.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sudden death, or unexpected natural death of a healthy individual, is a serious problem in all nations. Sudden cardiac death (SCD) mainly due to ischemic heart diseases is the top cause of sudden ...death. However, there are pathophysiological conditions, referred to as sudden arrhythmic death syndrome, in which no apparent lesion can be identified even after complete conventional or ordinary autopsy. While postmortem genetic analyses have accumulated evidence about underlying genetic abnormality in such cases, the precise relationships between genetic background and the phenotype have been largely elusive. In this study, a retrospective investigation of 17 autopsy cases in which lethal arrhythmia was suspected to be the cause of death was carried out. Genetic analysis focusing on 72 genes reported to be associated with cardiac dysfunctions was performed, in combination with detailed histopathological and postmortem imaging examination, and a family study. As a result, in two cases of suspected arrhythmogenic cardiomyopathy (ACM), we found a nonsense variant in
PKP2
and frameshift variant in
TRPM4
gene. In contrast, the other 15 cases showed no morphological changes in the heart despite the presence of a frameshift variant and several missense variants, leaving the clinical significance of these variants obscure. The findings of the present study suggest that nonsense and frameshift variants could be involved in the morphological abnormality in cases of SCD due to ACM, while missense variants alone rarely contribute to massive structural changes in the heart.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Dipeptidyl peptidase IV (DPP-4) inhibition is suitable mechanism for once daily oral dosing regimen because of its low risk of hypoglycemia. We explored linked bicyclic heteroarylpiperazines ...substituted at the γ-position of the proline structure in the course of the investigation of l-prolylthiazolidines. The efforts led to the discovery of a highly potent, selective, long-lasting and orally active DPP-4 inhibitor, 3-(2S,4S)-4-4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-ylpyrrolidin-2-ylcarbonylthiazolidine (8g), which has a unique structure characterized by five consecutive rings. An X-ray co-crystal structure of 8g in DPP-4 demonstrated that the key interaction between the phenyl ring on the pyrazole and the S2 extensive subsite of DPP-4 not only boosted potency, but also increased selectivity. Compound 8g, at 0.03mg/kg or higher doses, significantly inhibited the increase of plasma glucose levels after an oral glucose load in Zucker fatty rats. Compound 8g (teneligliptin) has been approved for the treatment of type 2 diabetes in Japan.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Fatty pancreas (FP) is characterized by pancreatic fat accumulation and the subsequent development of pancreatic and metabolic complications. However, FP has not been categorized in the manual for ...abdominal ultrasound in cancer screening and health check-ups in Japan, and the pathology of FP has not been fully elucidated.Nine hundred and nineteen people who underwent a medical check-up had the severity of their pancreatic fat accumulation categorized after transabdominal ultrasonographic examination. The relationships between FP, lifestyle-related diseases, and fatty liver disease at this time were assessed using stratification analysis.The prevalence of FP was 46.8% (430/919). People with FP were more likely to be male and had higher prevalences of lifestyle-related diseases, including fatty liver disease. Men and women were similarly represented in each tertile of pancreas brightness. Older age; high waist circumference, triglyceride and glucose index, serum low-density lipoprotein-cholesterol, hepatic steatosis index; and low serum amylase were associated with the presence of severe FP. Moreover, the group with severe liver steatosis had a higher prevalence of FP and a higher pancreatic brightness score. Logistic regression analysis showed that individuals with liver steatosis were more likely to have severe FP.The severity of FP is associated with features of lifestyle-related diseases and the severity of liver steatosis. These findings suggest that high visceral fat content is associated with more severe fatty pancreas as a phenotype of ectopic fat accumulation, as well as fatty liver disease.
Background
Myenteric ganglionitis is a disorder that causes intestinal motor dysfunction. It may be caused due to neoplastic, central nervous system, or systemic infectious disorders. However, some ...cases are considered to be idiopathic in origin.
Case presentation
A 33-year-old man was admitted to the hospital with sudden severe abdominal pain accompanied by watery diarrhea. Computed tomography imaging revealed edema of the entire small intestinal wall without ischemic changes. Detailed examination could not be performed for identifying the cause of abdominal pain because of the patient’s worsened general condition, and he died 7 days after onset. The autopsy results confirmed the cause of the patient’s severe abdominal pain as an idiopathic myenteric ganglionitis.
Conclusion
Some patients with idiopathic myenteric ganglionitis might die without a definitive diagnosis during their lifetime because of the rarity of this disease. When encountering severe intestinal motility abnormalities of unknown cause, physicians should consider idiopathic myenteric ganglionitis when choosing therapy.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The name “Actinomyces suis” was applied to each actinomycete isolate from swine actinomycosis by Grässer in 1962 and Franke in 1973. Nevertheless, this specific species was not included in the ...“Approved List of Bacterial Name” due to absence of the type cultures. Therefore, “Actinomyces suis” based on the description of Franke 1973 has been considered as “species incertae sedis”. We isolated a number of Actinomyces strains from swine. The representative strains of them was designated as Chiba 101 that was closely similar to the description in “Actinomyces suis” reported by Franke in 1973. Interestingly, it was found that the biological characteristics of these strains were also very similar to those of Actinomyces denticolens. Furthermore, the average nucleotide identity (ANI) value between strain Chiba 101 and the type-strain of Actinomyces denticolens (=DSM 20671T) was found to be 99.95%. Sequences of the housekeeping genes and 16S rRNA gene showed 100% homology. These results strongly suggested that “Actinomyces suis” Franke 1973 is the same species as Actinomyces denticolens. Since actinomycosis caused by Actinomyces denticolens have been demonstrated in horses recently, it is necessary to recognize that Actinomyces denticolens is the pathogenic actinomycetes in broader range of animals.
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