Effects of chemokine (C–C motif) ligand 1 on microglial function

AbstractMicroglia, which constitute the resident macrophages of the central nervous system (CNS), are generally considered as the primary immune cells in the brain and spinal cord. Microglial cells respond to various factors which are produced following nerve injury of multiple aetiologies and contribute to the development of neuronal disease. Chemokine (C–C motif) ligand 1 (CCL-1), a well-characterized chemokine secreted by activated T cells, has been shown to play an important role in neuropathic pain induced by nerve injury and is also produced in various cell types in the CNS, especially in dorsal root ganglia (DRG). However, the role of CCL-1 in the CNS and the effects on microglia remains unclear. Here we showed the multiple effects of CCL-1 on microglia. We first showed that CCR-8, a specific receptor for CCL-1, was expressed on primary cultured microglia, as well as on astrocytes and neurons, and was upregulated in the presence of CCL-1. CCL-1 at concentration of 1ng/ml induced chemotaxis, increased motility at a higher concentration (100ng/ml), and increased proliferation and phagocytosis of cultured microglia. CCL-1 also activated microglia morphologically, promoted mRNA levels for brain-derived neurotrophic factor (BDNF) and IL-6, and increased the release of nitrite from microglia. These indicate that CCL-1 has a role as a mediator in neuron-glia interaction, which may contribute to the development of neurological diseases, especially in neuropathic pain

Urinary adiponectin in DKD

Aims: Since diabetes-associated kidney complication changes from diabetic nephropathy to diabetic kidney disease (DKD), more suitable biomarkers than urinary albumin are required. It has been hypothesized that urinary adiponectin (u-ADPN) is associated with the progression of DKD. We therefore evaluated the effectiveness of u-ADPN in predicting the decline of the renal function in patients with diabetes prior to end-stage renal disease. Methods: An ultrasensitive immune complex transfer enzyme immunoassay (ICT-EIA) was used to measure total and high molecular weight (HMW) adiponectin separately. We evaluated the relationships between the creatinine-adjusted urinary total-ADPN and HMW-ADPN, albumin (UACR) and liver-type fatty acid binding protein (L-FABP) at baseline and the 2-year change of the estimated glomerular filtration rate (ΔeGFR). Results: This 2-year prospective observational study included 201 patients with diabetes. These patients were divided into three groups according to their ΔeGFR: ≤-10 ml/min/1.73m2, >-10 and ≤0 ml/min/1.73m2, and >0 ml/min/1.73m2. Jonckheere-Terpstra test showed that lower ΔeGFR was associated with higher u-HMW-ADPN (p = 0.045). In logistic regression analysis, u-HMW-ADPN was associated with ΔeGFR after adjusted age, sex, and basal eGFR. Conclusion: Urinary HMW-ADPN could predict a declining renal function in patients with diabetes

Sociodemographic factors affecting not receiving COVID-19 vaccine in Japan among people who originally intended to vaccinate: a prospective cohort study

ObjectiveVaccine hesitancy is a major issue for acquiring herd immunity. However, some individuals may go unvaccinated owing to inhibitory factors other than vaccine hesitancy. If there is even a small number of such people, support is needed for equitable vaccine distribution and acquiring herd immunity. We investigated sociodemographic factors that affected not undergoing COVID-19 vaccination in Japan among individuals who had strong intention to vaccinate before beginning the vaccination.MethodsWe conducted this prospective cohort study on workers aged 20–65 years from December 2020 (baseline), to December 2021 using a self-administered questionnaire survey. There were 27,036 participants at baseline and 18,560 at follow-up. We included 6,955 participants who answered yes to this question at baseline: “Would you like to receive a COVID-19 vaccine as soon as it becomes available?” We applied multilevel logistic regression analyses to examine the association between sociodemographic factors and being unvaccinated at follow-up.ResultsIn all, 289 participants (4.2%) went unvaccinated. The odds ratios (ORs) for being unvaccinated were significantly higher for participants aged 30–39 and 40–49 than those aged 60–65 years. Being divorced, widowed, or single, having low income, and having COVID-19 infection experience also had higher ORs.DiscussionWe found that some participants who initially had strong intention to vaccinate may have gone unvaccinated owing to vaccine side effects and the financial impact of absenteeism due to side effects. It is necessary to provide information repeatedly about the need for vaccination as well as social support to ensure that those who intend to vaccinate are able to do so when aiming for acquiring herd immunity through vaccination against COVID-19 as well as other potential infection pandemics in the future

Infrequent Mutation of Lysophosphatidic Acid Receptor-1 Gene in Hamster Pancreatic Duct Adenocarcinomas and Established Cell Lines

To evaluate the involvement of lysophosphatidic acid receptor-1 (LPA1) gene alteration in pancreatic carcinogenesis, we investigated mutations in the LPA1 gene in hamster pancreatic duct adenocarcinomas (PDAs) and established cell lines. Female Syrian golden hamsters received 30 mg/kg of N-nitrosobis(2-oxopropyl)amine (BOP) followed by repeated exposure to an augmentation pressure regimen consisting of a choline-deficient diet combined with DL-ethionine and then L-methionine and a further administration of 20 mg/kg BOP. A total of 10 PDAs obtained 10 weeks after beginning the experiment and three cell lines established from subcutaneously transplantable PDAs in syngeneic hamsters were examined for mutations using reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) analysis. A mutation was detected in only one PDA (1/10, 10%) in the form of a GGA to GTA (Gly to Val) transversion at codon 355, and no mutations were detected in the three cell lines. These results suggest that the LPA1 gene mutation may play roles in a limited fraction of BOP-induced pancreatic duct carcinogenesis in hamsters

ニクガンテキ モンミャク シンシュウ ヨウセイ カンガン セツジョゴ ノ Systemic IFN＋Low dose FP ノ ユウヨウセイ : リロンテキ コンキョ ト リンショウテキ コウカ

Background and Aims : Despite a recent progress of treatment for hepatocellular carcinoma （HCC）, the prognosis of advanced HCC with macroscopic vascular invasion remains unsatisfactory. We investigated anti-tumor effect of IFNα using experimental model and show the outcome of our systemic adjuvant therapy consisting of IFNα,５FU and cisplatin（IFP）after hepatectomy on advanced HCC with macroscopic portal invasion. Methods［: Basic study］Anti-tumor effects such as inhibition of invasion, proliferation of pegylated IFN α２b（PegIFNα）was evaluated using MH１３４mouse HCC cells, in vitro and vivo. ［Clinical study］: Thirty patients who had HCC with Vp２or more of macroscopic portal invasion（Vp２; portal vein tumor thrombus in its２nd order branch）were included. Those patients were retrospectively divided into two groups : the systemic IFNα,５FU and cisplatin group （n＝１４, IFP group）; and the no adjuvant therapy group（n＝１６, control）. Clinicopathological variables were compared between the two groups, including patient survival and disease-free survival. Results［: Basic］In vitro, the proliferation was significantly suppressed by Peg-IFNα, and invasion potential was also inhibited. In vivo, tumor growth was significantly suppressed compared to control （０．５vs.５．０cm, p＜０．０５）, and liver metastases was decreased（number :１９vs.６, p＜０．０５）. ［Clinical］The overall and disease-free survival rate in IFP group was significantly higher than in control group（１y :１００％ vs３８％,３y :６５％ vs２５％, P＜０．０１,１y :３６％ vs２５％,３y :３６％ vs１９％, P＜０．０１）. Regarding the recurrent patterns,５of９patients in IFP group had controllable tumors in the remnant liver, although１２of１３patients in control group had distant metastasis or multiple recurrences in the residual liver. Conclusion : Our new adjuvant regimen of systemic IFP may be a promising strategy after radical resection for HCC with macroscopic portal invasion

Influence of primary and secondary prevention indications on anxiety about the implantable cardioverter-defibrillator

AbstractBackgroundImplantable cardioverter-defibrillators (ICDs) have been established for primary and secondary prevention of fatal arrhythmias. However, little is known about the influence of ICD indications on quality of life (QOL) and psychological disturbances. This study aimed to examine whether there were differences in QOL and psychological distress in patients that have an ICD for primary or secondary prevention of fatal arrhythmias.MethodsA multicenter survey of 179 consecutive outpatients (29.1% primary prevention) with ICD implantations completed the Short Form-8 (SF-8), Beck Depression Inventory (BDI), Impact of Event Scale-Revised (IES-R), State-Trait Anxiety Inventory (STAI), and Worries about ICD (WAICD).ResultsPatients with an ICD for primary prevention had a higher trait anxiety score and worries about ICD score than patients with an ICD for secondary prevention (41.7±12.4 vs. 34.7±12.3, p=0.001 and 39.6±18.0 vs. 30.0±18.9, p=0.002, respectively), even after adjusting for demographic and clinical characteristics. In multivariable analysis of variance, primary prevention ICD recipients reported a poorer QOL on the vitality subscale of the SF-8.ConclusionsIn our study population, which mostly consisted of New York Heart Association (NYHA) class I and II subjects, primary prevention ICD recipients were more prone to experience worries about their ICD, anxiety, and a poorer QOL compared to secondary prevention ICD recipients. In clinical practice, primary prevention ICD patients should be closely monitored. If warranted, they should be offered psychological intervention, as anxiety and low QOL were predictors of mortality

Clinical role of Foxp3+regulatory T cell in Living donor related liver transplantation for prediction of life-threatening complications

Purposes : It is no doubt that regulatory T cells (Foxp3+CD4+CD25+T cells : Treg) play important roles in transplant immunity.We investigated the significance of Treg expression in acute stage of living donorrelated liver transplantation (LDLT) for the possibility of the sensitive marker for immunological state and homeostatic stress after liver transplantation. Methods : Peripheral blood was drawn from 5 recipients of LDLT preoperatively and on post operative 1, 4, 7, and 14 days. The peripheral blood mononuclear cells (PBMCs) were stained with CD4, CD25, Foxp3, and were analyzed with FACScan. This data was compared with clinical output of LDLT. Result : The populations of Treg were significantly decreased in all patients on day 1 after LDLT and significantly increased in patients who had early postoperative complications compared with patients who had no complications. Conclusions : The population of Treg in peripheral blood may reflect the surgical stress such as life-threatening complications after LDLT

Atypically large well-differentiated hepatocellular carcinoma with extensive fatty metamorphosis : Report of a Case

A large well-differentiated hepatocellular carcinoma (HCC) with fatty change is rare, and to date only a few cases have been reported. Herein, we present a 68-year-old man who developed a well-differentiated HCC with extensive fatty metamorphosis. The patient was referred to our institute because of a rapidly growing tumor in the left lobe of the liver. Ultrasonography showed a hyperechoic lesion with a peripheral hypoechoic area. Dynamic contrast-enhanced computed tomography (CT) scan in all three phases revealed the tumor which showed diffuse low attenuation with internal irregular enhancement. He underwent left lateral segmentectomy at the liver. Histological diagnosis confirmed well-differentiated HCC and the surrounding non-cancerous area was diagnosed as non-alcoholic steatohepatitis. The patient is still alive without recurrence after 17 months of follow-up