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The article presents the case study of a 59-year-old Japanese woman who had a persistent skin eruption located on the face for 5 years' duration. These asymptomatic yellowish papules had gradually increased in number. She had approximately 30 lesions, 1-3 mm in diameter, with a smooth surface. Histopathology of the lesion excised from her right cheek showed a cyst in the mid-dermis that was lined by 3-4 cell layers of undulating squamous epithelium. Steatocystoma multiplex is an inherited disease with an autosomal, dominant pattern. Sporadic form is also noted.

Presents the clinical discourse of two patients with anaphylactic symptoms induced by a chloral hydrate suppository, which contained gelatin, used for sedation before an electroencephalography. Acquisition and mechanism of gelatin allergy; Medical background of the patients; Characteristics common to the patients.

Aim: This study aimed to elucidate whether personality traits modify the relationship between nausea and vomiting of pregnancy (NVP) and anxiety, stratified by three pregnancy periods: 5–8 weeks, 9–12 weeks, and 13–20 weeks. Methods: This longitudinal study was conducted from August 2018 to February 2019 at a perinatal outpatient unit in a general hospital. We included 153 pregnant women aged ≥20 years and under 20 weeks of gestation at their first prenatal visit. They completed the Index of Nausea, Vomiting, and Retching, and the State–Trait Anxiety Inventory (STAI) to measure anxiety in terms of both trait (STAI‐T) and state anxiety (STAI‐S), and retook them at follow‐up checkups for a maximum of three times. Results: Using longitudinal data until 20 weeks' gestation, changes in NVP and trait anxiety were significantly associated with changes in state anxiety independently, with trait anxiety being more strongly involved than the change in NVP. This tendency was pronounced in the high‐trait anxiety group with STAI‐T scores of ≥45. Cross‐sectional analyses by gestational week showed similar results in the low‐trait anxiety group (STAI‐T < 45). In the high‐trait anxiety group, only trait anxiety was significantly associated with state anxiety up to 12 weeks gestation. However, only NVP was significantly associated with state anxiety after 13 weeks. Conclusions: Pregnant women who tend to be anxious temperamentally may have other factors that cause anxiety besides nausea immediately after the discovery of pregnancy. Understanding personality traits may help reduce anxiety in pregnant women. [ABSTRACT FROM AUTHOR]

Food protein-induced enterocolitis (FPIE) is a severe, cell-mediated gastrointestinal food hypersensitivity typically provoked by cow's milk [Joint Task Force of AAAAI and ACAAI Food allergy: a practice parameter. XVII. Differential diagnosis of adverse reaction to foods. Ann Allergy Asthma Immunol 96(3 Suppl 2):S40-S44 (2006)]. We present an infant who developed FPIE associated with enterotoxigenic E. coli (ETEC) and methicillin-resistant Staphylococcus aureus (MRSA) infections. The case suggests that enteral infection may have a role in the development of sensitization to food protein and the pathogenesis of FPIE. [ABSTRACT FROM AUTHOR]

Reports a salivary-type hyperamylasemia in an asthmatic boy who received an overdose of aminophylline infusions and subsequent inhalation of Β1-agonist. Details of the medical history of the patient; Conditions under which salivary-type of hyperamylasemia is observed.

Discusses the steroid-sparing effect of tacrolimus in patients with juvenile dermatomyositis. Result of the treatment of Gottron papules with prednisolone; Reason for the discontinued use of methotrexate; Impact of tacrolimus on the muscle strength of the patient.

Neuroendocrine tumors (NETs) arise from neuroendocrine cells and are mostly observed in the gastrointestinal tract, pancreas, and lungs. NETs in the oral and maxillofacial region are extremely rare. We report a case of a 59-year-old woman with an NET in the mandible. The patient did not show any symptoms except for remarkable swelling and bleeding. The lesion appeared as a radiolucent honeycomb abnormality with bone destruction on panoramic radiography. The histopathologic diagnosis following a biopsy was NET. Contrast-enhanced computed tomography (CT), 18 F-fluorodeoxyglucose positron emission computed tomography ( 18 F-FDG PET/CT), and adrenal scintigraphy-labeled meta-iodobenylguanidine were the modalities added to identify the primary site. Multiple lesions were confirmed in the gastrointestinal tract. Endoscopy was performed to identify the lesions, and several lesions were observed protruding from the mucous membranes. However, the endoscopy specimens did not yield an accurate diagnosis because adequate samples were not acquired. Blood and urine tests revealed no functional activity caused by the tumors. Although the origin was not histopathologically confirmed with endoscopy, this patient was situationally diagnosed with nonfunctional NET originating from the duodenum, as demonstrated by the metastases in the mandible. [ABSTRACT FROM AUTHOR]

Objective Dysregulated chemokine signaling contributes to autoimmune diseases by facilitating aberrant T cell infiltration into target tissues, but the specific chemokines, receptors, and T cell populations remain largely unidentified. The aim of this study was to examine the role of the potent chemokine CXCL12 and its receptor CXCR4 in the T cell autoimmune response, using alymphoplasia ( aly)/ aly mice, a model of Sjögren's syndrome ( SS). Methods T cell phenotypes in the salivary gland of aly/aly mice were evaluated using immunologic analysis. An in vitro migration assay was used to assess T cell migratory activity toward several chemokines. Gene expression of chemokine receptors and transforming growth factor β receptors ( TGFβRs) was measured by quantitative reverse transcription-polymerase chain reaction. The CXCR4 antagonist AMD3100 was administered to the aly/aly mice in order to evaluate its suppressive effect on autoimmune lesions. Results Effector memory T ( TEM) cells derived from aly/aly mice demonstrated higher in vitro migratory activity toward CXCL12 than did TEM cells from aly/+ mice. CXCL12 expression was specifically up-regulated in the SS target cells of aly/aly mice. TEM cells from RelB−/− mice, but not Nfkb1−/− mice, also showed high migratory activity toward CXCL12, implicating a role of the nonclassical RelB/ NF-κB2 pathway in the regulation of TEM cell migration. TEM cells from aly/aly mice also overexpressed TGFβR type I ( TGFβ RI) and TGFβ RII. The CXCR4 antagonist AMD3100 suppressed autoimmune lesions in aly/aly mice by reducing TEM cell infiltration. Conclusion Our results suggest that the RelB/ NF-κB2 pathway regulates T cell migration to autoimmune targets through TGFβ/ TGFβR-dependent regulation of CXCL12/ CXCR4 signaling. This suggests that these signaling pathways are potential therapeutic targets for the treatment of autoimmune diseases. [ABSTRACT FROM AUTHOR]

Allergic contact hypersensitivity to metals is a delayed-type allergy. Although various metals are known to produce an allergic reaction, nickel is the most frequent cause of metal allergy. Researchers have attempted to elucidate the mechanisms of metal allergy using animal models and human patients. Here, the immunological and molecular mechanisms of metal allergy are described based on the findings of previous studies, including those that were recently published. In addition, the adsorption and excretion of various metals, in particular nickel, is discussed to further understand the pathogenesis of metal allergy. [ABSTRACT FROM AUTHOR]

Background. Mechanically ventilated critically ill patients need the opportunity to communicate their physical and psychosocial concerns to nurses. However, these patients face the unique problem of lacking even the opportunity to communicate. Aims. The study aimed to describe the characteristics of communication opportunities for critically ill mechanically ventilated patients. Methods. The study was designed as a video-based descriptive observational study. Participants included seven mechanically ventilated critically ill patients at the intensive care unit, coronary care unit, or high care unit who were conscious and seven registered nurses (seven pairs). Videos were recorded continuously from 8 am to 4 pm, and the footage was then descriptively analyzed. Data collection took place between July 2019 and June 2020. Results. The total recording time was 668.0 minutes. Of these 668.0 minutes, nurses stayed in the Conversation Area of the Patient for 279.6 minutes, and of these 279.6 minutes, two-way face-to-face communication between nurse and patient occurred for 78.0 minutes. Of these 78.0 minutes, communications were started by nurses for 47.2 minutes (174 scenes) and by patients for 24.2 minutes (36 scenes). The patient-started two-way communication scenes included 37 instances of Patient-Intentional-Action that triggered the start of communication. Actions using the upper limbs were observed in 20 instances and represented the most frequently used body part. The head/face, lower limbs, or trunk were also used in some of the actions. Gestures were the most commonly used action type (14 instances). Other types included lip movement, grimace, leg flex/extension, and cough. Conclusions. We found that nurses tended to start communication more frequently than patients did and that patients demonstrated Patient-Intentional-Action with a variety of actions using various body parts. Communication opportunities for patients were created when nurses took the initiative to start communication or when they noticed and responded to the Patient-Intentional-Action. Our findings demonstrate that nurses need to recognize and always respond to Patient-Intentional-Action and to take the initiative in communicating rather than waiting for the patient to do so. [ABSTRACT FROM AUTHOR]

Background: Topical therapy is effective for dry eye, and its prolonged effects should help in maintaining the quality of life of patients with dry eye. We previously reported that the oral administration of rebamipide (Reb), a mucosal protective agent, had a potent therapeutic effect on autoimmune lesions in a murine model of Sjögren's syndrome (SS). However, the effects of topical treatment with Reb eyedrops on the ocular lesions in the murine model of SS are unknown. Methods and Finding: Reb eyedrops were administered to the murine model of SS aged 4–8 weeks four times daily. Inflammatory lesions of the extraorbital and intraorbital lacrimal glands and Harderian gland tissues were histologically evaluated. The direct effects of Reb on the lacrimal glands were analyzed using cultured lacrimal gland cells. Tear secretions of Reb-treated mice were significantly increased compared with those of untreated mice. In addition to the therapeutic effect of Reb treatment on keratoconjunctivitis, severe inflammatory lesions of intraorbital lacrimal gland tissues in this model of SS were resolved. The mRNA expression levels of IL-10 and mucin 5Ac in conjunctival tissues from Reb-treated mice was significantly increased compared with those of control mice. Moreover, lactoferrin production from lacrimal gland cells was restored by Reb treatment. Conclusion: Topical Reb administration had an anti-inflammatory effect on the ocular autoimmune lesions in the murine model of SS and a protective effect on the ocular surfaces. [ABSTRACT FROM AUTHOR]

Peripheral T cells are maintained by the apoptosis of activated T cells through the Fas-Fas ligand system. Although it is well known that normal T cells fail to survive in the Fas-deficient immune condition, the molecular mechanism for the phenomenon has yet to be elucidated. In this study, we demonstrate that rapid cell death and clearance of normal T cells were induced by Fas-deficient Ipr macrophages. Transfer of normal T cells into Ipr mice revealed that Fas expression on donor T cells was promptly enhanced through the IFN-Ɣ/IFN-ƔR. In addition, Fas ligand expression and phagocytic activity of Ipr macrophages were promoted through increased NF-KB activation. Controlling Fas expression on macrophages plays an essential role in maintaining T cell homeostasis in the peripheral immune system. Our data suggest a critical implication to the therapeutic strategies such as transplantation and immunotherapy for immune disorder or autoimmunity related to abnormal Fas expression. [ABSTRACT FROM AUTHOR]

Abstract: We have recently demonstrated that reactive oxygen species (ROS) play an important role in RAW264.7 cell apoptosis induced by cationic liposomes composed of stearylamine (SA-liposomes). In this study, we investigated whether protein kinase Cδ PKCδ) is involved in apoptosis induced by cationic liposomes. Tyrosine phosphorylation, nuclear localization, and cleavage of PKCδ were observed following the treatment of cells with SA-liposomes, suggesting that SA-liposomes activate PKCδ. Rottlerin, a specific inhibitor of PKCδ, inhibited ROS generation and also suppressed apoptosis. Cell surface proteoglycans may contribute to PKCδ activation by SA-liposomes. These findings suggest that PKCδ is strongly associated with apoptosis induced by SA-liposomes. [Copyright &y& Elsevier]

Abstract: Airway inflammation is accompanied by structural changes, termed remodeling, that lead to lung dysfunction over the long term. Although both endothelin-1 (ET-1) and cysteinyl leukotrienes (CysLTs) appear to be involved in airway remodeling in several lung diseases, how these molecules interact remains largely unknown. In this study, we examined the effects of leukotriene (LT) D4 on the function of ET-1-primed fibroblasts. ET-1 at 10−7 M up-regulated the expression of the CysLT receptors at both the mRNA and protein levels in human lung fibroblasts. LTD4 enhanced matrix metalloproteinase-2 and pro-collagen production, and α-smooth muscle actin expression of ET-1-primed fibroblasts, but had little or no effect on unprimed fibroblasts. The CysLT1 receptor antagonist montelukast completely abrogated the effects of LTD4. Our data suggested that LTD4 may act as a precipitating factor during ET-1-mediated airway remodeling and that CysLT1 receptor antagonists may have a role in preventing aberrant extracellular matrix degradation. [Copyright &y& Elsevier]

Objective: In recent years, natural language processing (NLP) techniques have progressed, and their application in the medical field has been tested. However, the use of NLP to detect symptoms from medical progress notes written in Japanese, remains limited. We aimed to detect 2 gastrointestinal symptoms that interfere with the continuation of chemotherapy—nausea/vomiting and diarrhea—from progress notes using NLP, and then to analyze factors affecting NLP. Materials and methods: In this study, 200 patients were randomly selected from 5277 patients who received intravenous injections of cytotoxic anticancer drugs at Kagawa University Hospital, Japan, between January 2011 and December 2018. We aimed to detect the first occurrence of nausea/vomiting (Group A) and diarrhea (Group B) using NLP. The NLP performance was evaluated by the concordance with a review of the physicians' progress notes used as the gold standard. Results: Both groups showed high concordance: 83.5% (95% confidence interval [CI] 74.1-90.1) in Group A and 97.7% (95% CI 91.3-99.9) in Group B. However, the concordance was significantly better in Group B (P =.0027). There were significantly more misdetection cases in Group A than in Group B (15.3% in Group A; 1.2% in Group B, P =.0012) due to negative findings or past history. Conclusion: We detected occurrences of nausea/vomiting and diarrhea accurately using NLP. However, there were more misdetection cases in Group A due to negative findings or past history, which may have been influenced by the physicians' more frequent documentation of nausea/vomiting. [ABSTRACT FROM AUTHOR]

Unlabelled: OBJECTIVE; To examine the effects of diet and diet with voglibose or glyburide on abdominal adiposity and metabolic abnormalities in patients with type 2 diabetes.Research Design and Methods: A total of 36 Japanese patients with newly diagnosed type 2 diabetes (50.8 +/- 8.6 years of age, BMI 24.5 +/- 3.5 kg/m(2)) and 273 normal control subjects were studied. The patients were treated for 3 months with diet alone (30 kcal/kg per day) (n = 15), diet with voglibose (n = 12), or diet with glyburide (n = 9). They underwent 75-g oral glucose tolerance testing, assessment of insulin sensitivity (SI), and acute insulin response (AIR) with intravenous glucose tolerance testing based on the minimal model, and measurement of abdominal visceral adipose tissue area (VAT) and subcutaneous adipose tissue area (SAT) by computed tomography before and after treatment.Results: The diabetic patients had comparable SAT but larger VAT than the control subjects. With a mean weight loss of 2-3 kg, VAT and SAT were decreased similarly in all treatment groups. The VAT-to-SAT ratio was decreased only in the voglibose group. Glycemic control and serum lipid profiles were improved in all groups. Changes in glycemic control after diet were closely correlated with changes in VAT but not with changes in SAT. SI and AIR were unchanged in the diet group but were improved in the voglibose and glyburide groups.Conclusions: In Japanese patients with newly diagnosed type 2 diabetes who were relatively lean but had excess VAT, diet with or without voglibose or glyburide effectively reduced VAT. Decrease in VAT was closely associated with improvement of glycemic control with diet. Additional use of voglibose or low-dose glyburide had no detrimental effects on abdominal adiposity and had beneficial effects on SI and AIR. [ABSTRACT FROM AUTHOR]

Chyle leaks are attributed to damage to the thoracic duct itself or its tributaries during surgery. Chylothorax after lung cancer surgery can occur due to damaged thoracic duct tributaries; however, little is known of the mechanism involved. A 71‐year‐old female underwent a left upper lobectomy with hilar and mediastinal lymphadenectomy for a 1.8‐cm primary squamous cell carcinoma, and developed a chylothorax a day later. Catheter lymphangiography revealed high‐flow chyle leaks from a damaged thoracic duct tributary, known as a bronchomediastinal lymph trunk, due to a lymphatic reflex from the thoracic duct. Subsequently, catheter embolization of the tributary repaired the chylothorax. The potential for persistent chylothorax after lung cancer surgery and successful lymphatic intervention should be noted. [ABSTRACT FROM AUTHOR]

Human herpesvirus-6 (HHV-6) reactivation is an important complication in patients receiving umbilical cord blood transplantation (CBT). Chromosomally integrated human herpesvirus-6 (ciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the host germline genome and is transmitted in a Mendelian manner. The influence of ciHHV-6 in recipients or donors in cases of CBT is unknown. We report the first case with ciHHV-6 that received CBT twice for acute lymphoblastic T-cell leukemia. HHV-6 DNA in peripheral blood leukocytes (PBLs) was examined over time through two CBTs. After the first CBT, the HHV-6 viral load was significantly reduced by conversion to PBLs derived from the first donor. During the second CBT, an increase in HHV-6 DNA in PBLs and plasma were observed. However, HHV-6 mRNA was not detected in either the sample before 2nd CBT or at the time of HHV-6 DNA elevation. It is considered that the HHV-6 DNA detected in PBLs and plasma samples might be the HHV-6 genome released due to tissue damage. This case suggests that physicians should be aware of HHV-6 DNA variability during allogeneic hematopoietic stem cell transplantation in ciHHV-6 patients. [ABSTRACT FROM AUTHOR]

Background: Nanomaterials are widely used in various fields. Although the toxicity of carbon nanotubes (CNTs) in pulmonary tissues has been demonstrated, the toxicological effect of CNTs on the immune system in the lung remains unclear. Methods and finding: In this study, exposure to Taquann-treated multi-walled CNTs (T-CNTs) was performed using aerosols generated in an inhalation chamber. At 12 months after T-CNT exposure, alveolar inflammation with macrophage accumulation and hypertrophy of the alveolar walls were observed. In addition, fibrotic lesions were enhanced by T-CNT exposure. The macrophages in the bronchoalveolar lavage fluid of T-CNT-exposed mice were not largely shifted to any particular population, and were a mixed phenotype with M1 and M2 polarization. Moreover, the alveolar macrophages of T-CNT-exposed mice produced matrix metalloprotinase-12. Conclusions: These results suggest that T-CNT exposure promoted chronic inflammation and fibrotic lesion formation in profibrotic macrophages for prolonged periods. [ABSTRACT FROM AUTHOR]

Polyethyleneimines (PEIs) are used for transfection of cells with nucleic acids. Meanwhile, the interaction of PEI with mitochondria causes cytochrome c release prior to apoptosis; the mechanisms how PEI causes this permeabilization of mitochondrial membranes and the release of cytochrome c remain unclear. To clarify these mechanisms, we examined the effects of branched-type PEI and linear-type PEI, each of which was 25 kDa in size, on mitochondria. The permeabilization potency of mitochondrial membranes by branched PEI was stronger than that by linear PEI. The permeabilization by PEIs were insensitive to permeability-transition inhibitors, indicating that PEI-induced permeabilization was not attributed to permeability transition. Meanwhile, PEIs caused permeabilization of artificial lipid vesicles; again, the permeabilization potency of branched PEI was stronger than that of linear PEI. Such a difference in this potency was close to that in the case of isolated mitochondria, signifying that the PEI-induced permeabilization of mitochondrial membranes could be attributed to PEI's interaction with the phospholipid phase. Furthermore, this PEI-induced permeabilization of the lipid vesicles was observed only in the case of lipid vesicles including negatively charged phospholipids. These results indicate that PEIs interacted with negatively charged phospholipids in the mitochondrial membranes to directly lead to their permeabilization. [ABSTRACT FROM AUTHOR]

Objective: Clear cell odontogenic carcinoma (CCOC) is a rare malignant odontogenic tumor (MOT) characterized by sheets and lobules of vacuolated and clear cells. To understand the biology of CCOC, we established a new cell line, CCOC-T, with EWSR1-ATF1 fusion gene from a mandible tumor with distant metastasis and characterized this cell line.Materials and Methods: To detect the EWSR1-ATF1 fusion gene, we used three CCOC cases, including the present case, by RT-PCR and FISH analysis. We characterized established CCOC-T cells by checking cell growth, invasion and the expression of odontogenic factors and bone-related factors. Moreover, the gene expression profile of CCOC-T cells was examined by microarray analysis.Results: Histologically, the primary tumor was comprised of cords and nests containing clear and squamoid cells separated by fibrous septa. In addition, ameloblastomatous islands with palisaded peripheral cells were observed, indicating probable odontogenic origin. This tumor expressed the fusion gene EWSR1-ATF1, which underlies the etiology of hyalinizing clear cell carcinoma (HCCC) and potentially that of CCOC. We found a breakpoint in the EWSR1-ATF1 fusion to be the same as that reported in HCCC. Established CCOC-T cells grew extremely slowly, but the cells showed highly invasive activity. Moreover, CCOC-T cells expressed bone-related molecules, odontogenic factors, and epithelial mesenchymal transition (EMT)-related molecules.Conclusion: To the best of our knowledge, this is the first report on the establishment of a CCOC cell line. CCOC-T cells serve as a useful in vitro model for understanding the pathogenesis and nature of MOT. [ABSTRACT FROM AUTHOR]

The mitochondrial calcium uniporter (MCU) complex is a highly-selective calcium channel, and this complex is believed to consist of a pore-forming subunit, MCU, and its regulatory subunits. As yeast cells lack orthologues of the mammalian proteins, the yeast expression system for the mammalian calcium uniporter subunits is useful for investigating their functions. We here established a yeast expression system for the native-form mouse MCU and 4 other subunits. This expression system enabled us to precisely reconstitute the properties of the mammalian MCU complex in yeast mitochondria. Using this expression system, we analyzed the essential MCU regulator (EMRE), which is a key subunit for Ca 2 + uptake but whose functions and structure remain unclear. The topology of EMRE was revealed: its N- and C-termini projected into the matrix and the inter membrane space, respectively. The expression of EMRE alone was insufficient for Ca 2 + uptake; and co-expression of MCU with EMRE was necessary. EMRE was independent of the protein levels of other subunits, indicating that EMRE was not a protein-stabilizing factor. Deletion of acidic amino acids conserved in EMRE did not significantly affect Ca 2 + uptake; thus, EMRE did not have basic properties of ion channels such as ion-selectivity filtration and ion concentration. Meanwhile, EMRE closely interacted with the MCU on both sides of the inner membrane, and this interaction was essential for Ca 2 + uptake. This close interaction suggested that EMRE might be a structural factor for opening of the MCU-forming pore. [ABSTRACT FROM AUTHOR]

A novel series of 2-pyridyl-benzensulfonamide derivatives have been identified as selective and orally active TRPM8 antagonists via high throughput screening (HTS). Exploration of the structure–activity relationships of compound 1 has led to the identification of RQ-00203078 (compound 36 ) as a highly selective, potent and orally available TRPM8 antagonist. RQ-00203078 demonstrated excellent in vivo activity in a dose dependent manner with an ED 50 value of 0.65 mg/kg in the icilin-induced wet-dog shakes model in rats after oral administration and may become an important pharmacological tool for fully assessing the potential therapeutic use of the targets activated by cold stimulation. [ABSTRACT FROM AUTHOR]

Background: Although autoimmunity in MRL/lpr mice occurs due to a defect in Fas-mediated cell death of T cells, the role of Fas-independent apoptosis in pathogenesis has rarely been investigated. We have recently reported that receptor activator of nuclear factor (NF)-kB ligand (RANKL)-activated dendritic cells (DCs) play a key role in the pathogenesis of rheumatoid arthritis (RA) in MRL/lpr mice. We here attempted to establish a new therapeutic strategy with RANKL-activated DCs in RA by controlling apoptosis of peripheral T cells. Repeated transfer of RANKL-activated DCs into MRL/lpr mice was tested to determine whether this had a therapeutic effect on autoimmunity. Methods and Finding: Cellular and molecular mechanisms of Fas-independent apoptosis of T cells induced by the DCs were investigated by in vitro and in vivo analyses. We demonstrated that repeated transfers of RANKL-activated DCs into MRL/lpr mice resulted in therapeutic effects on RA lesions and lymphoproliferation due to declines of CD4+ T, B, and CD4- CD8- double negative (DN) T cells. We also found that the Fas-independent T-cell apoptosis was induced by a direct interaction between tumor necrosis factor (TNF)-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) on T cells and TRAIL on Fasdeficient DCs in MRL/lpr mice. Conclusion: These results strongly suggest that a novel Fas-independent apoptosis pathway in T cells maintains peripheral tolerance and thus controls autoimmunity in MRL/lpr mice [ABSTRACT FROM AUTHOR]

Background: Although the activation of dermal dendritic cells (DCs) or Langerhans cells (LCs) via p38 mitogen-activated protein kinase (MAPK) plays a crucial role in the pathogenesis of metal allergy, the in vivo molecular mechanisms have not been identified and a possible therapeutic strategy using the control of dermal DCs or LCs has not been established. In this study, we focused on dermal DCs to define the in vivo mechanisms of metal allergy pathogenesis in a mouse nickel (Ni) allergy model. The effects of DC therapy on Ni allergic responses were also investigated. Methods and Finding: The activation of dermal DCs via p38 MAPK triggered a T cell-mediated allergic immune response in this model. In the MAPK signaling cascade in DCs, Ni potently phosphorylated MAP kinase kinase 6 (MKK6) following increased DC activation. Ni-stimulated DCs could prime T cell activation to induce Ni allergy. Interestingly, when MKK6 genetransfected DCs were transferred into the model mice, a more pronounced allergic reaction was observed. In addition, injection of short interfering (si) RNA targeting the MKK6 gene protected against a hypersensitivity reaction after Ni immunization. The cooperative action between T cell activation and MKK6-mediated DC activation by Ni played an important role in the development of Ni allergy. Conclusions: DC activation by Ni played an important role in the development of Ni allergy. Manipulating the MKK6 gene in DCs may be a good therapeutic strategy for dermal Ni allergy. [ABSTRACT FROM AUTHOR]

When pDHA4, a vector carrying all five pfaA– pfaE genes responsible for docosahexaenoic acid (DHA; 22:6) biosynthesis in Moritella marina MP-1, was coexpressed in Escherichia coli with the individual pfaA– pfaD genes for eicosapentaenoic acid (EPA; 20:5) biosynthesis from Shewanella pneumatophori SCRC-2738, both polyunsaturated fatty acids were synthesized only in the recombinant carrying pfaB for EPA synthesis. Escherichia coli coexpressing a deleted construct comprising pfaA, pfaC, pfaD and pfaE for EPA and pfaB for DHA produced EPA and DHA. Both EPA and DHA were detected in bacteria that inherently contained pfa genes for DHA. These results suggest that PfaB is the key enzyme determining the final product in EPA or DHA biosynthesis. [ABSTRACT FROM AUTHOR]

The transcription factor Nrf2 regulates the expression of antioxidant genes. Hyperglycemia-induced oxidative stress is involved in the pathogenesis of diabetes and its complications. However, little is known about the protective role of Nrf2 in diabetes. To gain insight into the protective role of Nrf2 in diabetes we treated Nrf2 knockout (Nrf2 KO) mice with streptozotocin (STZ). The STZ Nrf2 KO mice did not develop renal hyperfiltration, which was observed in the STZ-treated wild-type (STZ WT) mice, but renal function gradually deteriorated over the 10-week observation period. Urinary excretion of nitric oxide metabolites and the occurrence of 8-nitroguanosine, which was detected in glomerular lesions, were increased in STZ Nrf2 KO mice during the early stages after treatment. In vivo electron paramagnetic resonance analysis revealed an accelerated rate of decay of the 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl spin probe signal in STZ Nrf2 KO mice. The addition of superoxide dismutase prolonged the half-life of the signal, which suggested that increased oxygen radical formation occurred in the STZ Nrf2 KO mice. These results suggested that hyperglycemia increased oxidative and nitrosative stress and accelerated renal injury in the Nrf2 KO mice and that Nrf2 serves as a defense factor against some diabetic complications. [ABSTRACT FROM AUTHOR]

Abstract: The colony-forming ability of Escherichia coli genetically engineered to produce eicosapentaenoic acid (EPA) grown in 3mM hydrogen peroxide (H2O2) was similar to that of untreated cells. It was rapidly lost in the absence of EPA. H2O2-induced protein carbonylation was enhanced in cells lacking EPA. The fatty acid composition of the transformants was unaffected by H2O2 treatment, but the amount of fatty acids decreased in cultures of cells lacking EPA and increased in cultures of cells producing EPA, suggesting that cellular EPA is stable in the presence of H2O2 in vivo and may protect cells directly against oxidative damage. We discuss the possible role of EPA in partially blocking the penetration of H2O2 into cells through membranes containing EPA. [Copyright &y& Elsevier]

Aims: To study the possibility of constructing a remote interpretation system for retinal images.Methods: An ultra-widefield (UWF) retinal imaging device was installed in the internal medicine department specializing in diabetes to obtain fundus images of patients with diabetes. Remote interpretation was conducted at Nagoya City University using a cloud server. The medical data, severity of retinopathy, and frequency of ophthalmologic visits were analyzed.Results: Four hundred ninety-nine patients (mean age, 62.5 ± 13.4 years) were included. The duration of diabetes in 240 (48.1%) patients was less than 10 years and 433 (86.7%) patients had a hemoglobin (Hb) A1c below 8%. Regarding the retinopathy severity, 360 (72.1%) patients had no diabetic retinopathy (NDR), 63 (12.6%) mild nonproliferative retinopathy (NPDR), 38 (7.64%) moderate NPDR, 13 (2.6%) severe NPDR, and 25 (5.0%) PDR. Two hundred forty-one (48.3%) patients had an ophthalmologic consultation within 1 year, 104 (20.8%) had no history of an ophthalmologic consultation. DR was not present in 86 (82.7%) patients who had never had an ophthalmologic examination, 30 (78.9%) patients with severe NPDR or PDR had had an ophthalmologic visit within 1 year. The frequency of ophthalmic visits was correlated negatively with age, diabetes duration, HbA1c, and severity of retinopathy.Conclusion: Remote interpretation of DR using UWF retinal imaging was useful for retinopathy screening. During the COVID-19 pandemic, a remote screening system that can ensure compulsory social distancing and reduce the number of ophthalmic visits can be a safe system for patients and clinicians. [ABSTRACT FROM AUTHOR]