HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis-like Rats by Intravenous Injection of HTLV-1-producing Rabbit or Human T-Cell Line into Adult WKA Rats

We intravenously injected Ra-1 cells or MT-2 cells into female adult WKA rats. Spastic paraparesis mainly in the hind-limbs was observed in 1 out of 2 Ra-1 cell-injected WKA rats and in 3 out of 8 MT-2 cell-injected WKA rats 20 27 months after injection. The main neuropathological finding was symmetrical white matter degeneration with mononuclear cell infiltration of the spinal cord, similar to that of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients, and degeneration of nerve roots and peripheral nerves. Antibodies against HTLV-1 antigens were detected in plasma and cerebrospinal fluid from these HAM/TSP-like rats. HTLV-1 provirus was detected from the peripheral blood mononuclear cells of one of these rats 20 months after injection. Interestingly, spastic paraparesis was not observed in F344 rats.     

The degree of microRNA-34b/c methylation in serum-circulating DNA is associated with malignant pleural mesothelioma

Objectives

Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. microRNA-34b/c (miR-34b/c), which plays an important role in the pathogenesis of MPM, is frequently downregulated by DNA methylation in approximately 90% of MPM cases. In this study, we estimated the degree of miR-34b/c methylation in serum-circulating DNA using a digital methylation specific PCR assay (MSP).

Materials and methods

A real-time MSP assay was performed using the SYBR Green method. The melting temperature (Tm) of each PCR product was examined using a melting curve analysis. For a digital MSP assay, 40 wells were analyzed per sample. A total of 110 serum samples from 48 MPM cases, 21 benign asbestos pleurisy (BAP) cases, and 41 healthy volunteers (HVs) were examined.

Results

Positive range of Tm value for miR-34b/c methylation was defined as 77.71–78.79 °C which was the mean ± 3 standard deviations of 40 wells of a positive control. The number of miR-34b/c methylated wells was counted per sample according to this criterion. The number of miR-34b/c methylated wells in MPM cases was significantly higher than that in BAP cases (P = 0.03) or HVs (P < 0.001). Advanced MPM cases tended to have higher number of miR-34b/c methylated wells than early MPM cases. Receiver–operating characteristic (ROC) curve analysis revealed that three number of miR-34b/c methylated wells per sample was the best cut-off of positivity of MPM with a 67% of sensitivity and a 77% specificity for prediction. The area under the ROC curve was 0.77.

Conclusions

Our digital MSP assay can quantify miR-34b/c methylation in serum-circulating DNA. The degree of miR-34b/c methylation in serum-circulating DNA is associated with MPM, suggesting that this approach might be useful for the establishment of a new detection system for MPM.     

Synergistic effects of topoisomerase I inhibitor, 7-ethyl-10-hydroxycamptothecin, and irradiation in a cisplatin-resistant human small cell lung cancer cell line.

7-ethyl-10-[4-(1-piperidyl)-1-piperidyl] carbonyloxy-camptothecin, a topoisomerase I (topo I) inhibitor, is one of the most active agent against lung cancer, and its radiosensitizing effect has been reported recently. We evaluated a combination in vitro effect of irradiation and 7-ethyl-10-hydroxy-CPT (SN-38), an active metabolite of 7-ethyl-10-[4- (1-piperidyl)-1-piperidyl] carbonyloxy-camptothecin, on a human small cell lung cancer cell line (SBC-3) and its cisplatin-resistant subline (SBC-3/CDDP). Growth-inhibitory effects of irradiation with or without SN-38 were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A modified isobologram method was used to evaluate the treatment interaction. The combination of irradiation and SN-38 showed a synergistic inhibitory effect on the growth of SBC-3/CDDP despite its cross-resistance to irradiation and SN-38. In contrast, the same combination showed only an additive effect on the growth of parental SBC-3 cells. There was no significant difference in topo I protein expression between these two cell lines. In SBC-3 cells, topo I catalytic activity was suppressed by 4 Gy of irradiation, without a decrease of nuclear topo I protein, whereas the exposure of SBC-3 cells to 1 microM SN-38 subsequent to irradiation showed no remarkable additional effects on both topo I activity and protein content. On the other hand, in SBC-3/CDDP cells, topo I activity was unchanged by irradiation, but the subsequent exposure to SN-38 gave rise to a decrease in topo I activity, which was accompanied by a significant decrease in the topo I protein content (P = 0.02). These observations may indicate that SN-38 induces sequestration of topo I onto DNA in radiation-treated SBC-3/CDDP cells and suggest that the synergistic effect of irradiation and SN-38 in SBC-3/CDDP cells was considered attributable to DNA repair-related enhanced recruitment of topo I onto the damaged DNA.     

Detailed Molecular Interactions between Respiratory Syncytial Virus Fusion Protein and the TLR4/MD-2 Complex In Silico

Molecular interactions between respiratory syncytial virus (RSV) fusion protein (F protein) and the cellular receptor Toll-like receptor 4 (TLR4) and myeloid differentiation factor-2 (MD-2) protein complex are unknown. Thus, to reveal the detailed molecular interactions between them, in silico analyses were performed using various bioinformatics techniques. The present simulation data showed that the neutralizing antibody (NT-Ab) binding sites in both prefusion and postfusion proteins at sites II and IV were involved in the interactions between them and the TLR4 molecule. Moreover, the binding affinity between postfusion proteins and the TLR4/MD-2 complex was higher than that between prefusion proteins and the TLR4/MD-2 complex. This increased binding affinity due to conformational changes in the F protein may be able to form syncytium in RSV-infected cells. These results may contribute to better understand the infectivity and pathogenicity (syncytium formation) of RSV.     

脂蛋白脂酶活化剂NO-1886抑制糖尿病兔动脉粥样硬化的形成

目的　合成化合物NO 1886 ,一种脂蛋白脂酶活化观察脂蛋白脂酶活化剂是否降低高脂 /高蔗糖饲料诱发的糖尿病新西兰兔的血浆葡萄糖并减轻其动脉粥样硬化。方法　给予高脂 /高蔗糖饲料升高新西兰兔血浆总胆固醇 ,甘油三酯和葡萄糖及降低高密度脂蛋白胆固醇而导致动脉粥样硬化。饲料中加入 1 0 %NO 1886进行治疗观察。分别在 0、4、8、12、16、2 0及 2 4wk从禁食过夜的兔耳静脉抽取血样测定葡萄糖和脂质水平。第 2 4周末 ,处死动物 ,分离主动脉 ,经苏丹Ⅳ染色固定脂质后 ,计算脂纹病变面积。结果　应用NO 1886后 ,实验动物血浆葡萄糖 ,总胆固醇和甘油三酯降低 ,高密度脂蛋白胆固醇增加。对动脉粥样硬化的发展具有抑制作用。结论　NO 1886不仅可改善脂质紊乱 ,而且可降低血浆葡萄糖 ,减轻糖尿病兔动脉粥样硬化     

Coronary artery lesion distribution in patients with chronic kidney disease undergoing percutaneous coronary intervention

PurposeTo determine the location of coronary atherosclerosis distribution observed in patients with chronic kidney disease (CKD).MethodsA cross-sectional study was conducted using the database of cardiovascular medicine data from Saitama Sekishinkai Hospital to clarify the association between renal function and angiographic characteristics of coronary atherosclerosis. In total, 3268 patients who underwent percutaneous coronary intervention were included. Propensity score matching revised the total to 1772. The association of renal function with the location and/or distribution of coronary atherosclerosis lesions was then examined.ResultsOverall, coronary lesion was observed in the left anterior descending coronary artery (LAD) in 56% patients, whereas 28% and 22% were in the right coronary artery (RCA) and left circumflex coronary artery (LCX), respectively. LAD was most affected and observed in 57% patients with stage 1 CKD. RCA was second-most affected, at 26% CKD stage 1, but it increased to 31%, 38%, and 59% in CKD 3, 4, and 5, respectively. In CKD 5 patients, the RCA was the most affected artery (59%), with 41% LAD lesions. Logistic regression analysis after propensity score matching showed that the odds ratios for an RCA lesion was 3.658 in CKD 5 (p = .025) compared with CKD 1 after adjusting for traditional risk factors.ConclusionThe prevalence of RCA lesions, but not LAD or LCX lesions, increased with increasing CKD stage. The pathophysiology of coronary atherosclerosis may differ by lesion location. Deterioration of renal function may affect progression of atherosclerosis more in the RCA than in the LAD or LCX.     

Successful Treatment of Nephrotic Syndrome Due to Collapsing Focal Segmental Glomerulosclerosis Accompanied by Acute Interstitial Nephritis

A 39-year-old woman was hospitalized for nephrotic syndrome. Laboratory test results showed increased serum creatinine levels and urinary excretions of beta-2-microglobulin, and N-acetyl-beta-D-glucosaminidase. A renal biopsy revealed collapsing focal segmental glomerulosclerosis (FSGS) and acute interstitial nephritis. Despite treatment with pulse steroid followed by oral high-dose glucocorticoids and cyclosporines, heavy proteinuria persisted. After low-density lipoprotein apheresis (LDL-A) therapy was initiated, her proteinuria gradually decreased, leading to complete remission. A repeat renal biopsy after treatment revealed no collapsing glomeruli. Immediate LDL-A should be performed to treat cases of collapsing FSGS poorly responding to other treatments.     

牛奶及其制品与乳腺癌关系的研究进展

乳腺癌是西方女性最常见的肿瘤,我国女性乳腺癌患者也逐年上升。和所有的肿瘤一样,乳腺癌的病因复杂多样,其中包括饮食因素。众多考察乳腺癌的流行病学研究提及奶及其制品的影响,但没能得出一致的结论。著名的美国护士健康研究也没有发现奶和奶制品摄入与乳腺癌发生有明显关系。汇总观察这些流行病学资料发现,奶酪能微弱地增加患乳腺癌的危险。动物研究表明,现代牛奶中富含的雌激素和胰岛素样生长因子（IGF）-I有明显的促进二甲基苯并蒽（DMBA）诱导的大鼠乳腺肿瘤的生长。系统介绍流行病学研究和实验室研究的最新成果,同时讨论牛奶中存在的可能影响乳腺癌发生的诸多成分,其中起促进作用的有饱和脂肪、各类激素和污染物,起保护作用的有钙、维生素D和一些脂肪酸。     

Retrospective study of cochlear implantations at a single facility focusing on postoperative complications

ObjectiveAlthough cochlear implantation (CI) is a relatively safe operation, postoperative complications sometimes occur. We reviewed the frequency and severity of complications of CI at our hospital. We compared our results with previously reported complications and considered measures to improve patient outcomes.MethodsThis retrospective study examined the medical records of 70 patients who received CI between March 2005 and December 2018. We collected the following data: age at the time of the first surgery, etiology of hearing impairment, date of implantation, type of implanted devices, and complications. Surgical complications were divided by time into perioperative, early, and late, and by severity into major or minor.ResultsRecords of 38 adults and 32 children were analyzed. Bilateral CI was performed in 16 patients, 8 of whom were sequential, and unilateral CI was performed in 54 patients. The total number of operations was 78 for 86 CI. Complications were observed in 15 of 78 operations (19%), and the rates of minor and major complications were 15% and 4%, respectively. Complication rates were 21% (8/39) for children and 10% (4/39) for adults. All of the perioperative and early complications were minor. There were three major complications, all of which were infections presenting with mastoiditis and subcutaneous or subperiosteal abscesses. One case required reimplantation twice because of recurrent mastoiditis and temporal abscess.ConclusionsThere was no significant difference in the incidence of complications between children and adults, but all major complications were infection in pediatric cases. Careful attention is needed to prevent postoperative infection.     

Simultaneous Duodenal Metal Stent Placement and EUS-Guided Choledochoduodenostomy for Unresectable Pancreatic Cancer

Patients with pancreatic cancer frequently suffer from both biliary and duodenal obstruction. For such patients, both biliary and duodenal self-expandable metal stent placement is necessary to palliate their symptoms, but it was difficult to cross two metal stents. Recently, endoscopic ultrasonography-guided choledochoduodenostomy (EUS-CDS) was reported to be effective for patients with an inaccessible papilla. We report two cases of pancreatic cancer with both biliary and duodenal obstructions treated successfully with simultaneous duodenal metal stent placement and EUS-CDS. The first case was a 74-year-old man with pancreatic cancer. Duodenoscopy revealed that papilla had been invaded with tumor and duodenography showed severe stenosis in the horizontal portion. After a duodenal uncovered metal stent was placed across the duodenal stricture, EUS-CDS was performed. The second case was a 63-year-old man who previously had a covered metal stent placed for malignant biliary obstruction. After removing the previously placed metal stent, EUS-CDS was performed. Then, a duodenal covered metal stent was placed across the duodenal stenosis. Both patients could tolerate a regular diet and did not suffer from stent occlusion. EUS-CDS combined with duodenal metal stent placement may be an ideal treatment strategy in patients with pancreatic cancer with both duodenal and biliary malignant obstruction.