Co‐localization of Bunina bodies and TDP‐43 inclusions in lower motor neurons in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron involvement with Bunina bodies (BBs) and transactivation response DNA protein 43 (TDP‐43) inclusions. We examined the spinal cord (n = 20), hypoglossal nucleus (n = 6) and facial nucleus (n = 5) from ALS patients to elucidate the relationship between BBs and TDP‐43 inclusions. BBs were found in the anterior horn in 16 of 20 cases, in the hypoglossal nucleus in all six cases and in the facial nucleus in four out of five cases. TDP‐43 inclusions were found in each region of all the cases. Co‐localization of BBs and TDP‐43 inclusions was found in 15.2% of total neurons in the anterior horn, 29.2% in the hypoglossal nucleus and 17.3% in the facial nucleus. The frequency of TDP‐43 inclusions was significantly higher in neurons with BBs than in those without in each region. Ultrastructurally, TDP‐43‐positive filamentous structures were intermingled with BBs. These findings suggest that there is a close relationship in the occurrence between BBs and TDP‐43 inclusions.     

Structure-Based Design of Substituted Piperidines as a New Class of Highly Efficacious Oral Direct Renin Inhibitors

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Macrophage Depletion Prior to Neospora caninum Infection Results in Severe Neosporosis in Mice

We observed that murine macrophages showed greater activation and increased interleukin 6 (IL-6), IL-12p40, and interferon gamma (IFN-γ) production during Neospora caninum infection. Many macrophages migrated to the site of infection. Furthermore, macrophage-depleted mice exhibited increased sensitivity to N. caninum infection. This study indicates that macrophages are required for achieving protective immunity against N. caninum.     

Complete nucleotide sequences of hepatitis B virus genomes associated with epidemic fulminant hepatitis

Pre-core/core mutants are frequently observed in patients with fulminant hepatitis. To investigate the extent of molecular characteristics of hepatitis B virus (HBV) genomes implicated in the development of fulminant hepatitis, full-length HBV genomes were sequenced directly from sera of two patients with epidemic fatal fulminant hepatitis, after amplification by the polymerase chain reaction. These two genomes, of 3215 nucleotides, were 99.6% identical, indicating that a common source of HBV potentially caused fulminant hepatitis. Thirty unique nucleotide mutations were commonly found in the two entire HBV genomes. Three were located in the stem-loop structure, changing this element to a more stable structure. Twenty-five unique amino acid substitutions were found in each open reading frame, except for the X and pre-surface 2 genes. One was located in the pre-surface 1 gene; two were in the surface gene; three were in the pre-core gene, including codons 28 (tryptophan to stop codon) and 29 (glycine to aspartic acid); eight were in the core gene; and 11 were in the polymerase gene. The pre-core mutations at codons 28 and 29 were common to the two HBV strains reported previously in patients with epidemic fulminant hepatitis. Thus, HBV genomes associated with epidemic fatal fulminant hepatitis have numerous unique mutations, located mainly in the polymerase gene, as well as the pre-core/core gene, including mutations in the stem-loop structure of the pregenome encapsidation signal sequence. These mutations may be associated with the development of fulminant hepatitis. © 1996 Wiley-Liss, Inc.     

Low prevalence of anti-hepatitis C virus antibodies in female hemodialysis patients without blood transfusion: A multicenter analysis

To investigate whether nosocomial infection with hepatitis C virus (HCV) in chronic hemodialysis patients is related primarily to hemodialysis procedures, a multicenter analysis was carried out on 2,132 chronic hemodialysis patients (male: 1,274, female: 858) from 23 dialysis units using a second-generation anti-HCV antibody assay. The prevalence of anti-HCV antibodies in patients with blood transfusion (29.9%) was significantly higher (P < .0001) than in those without blood transfusion (7.6%). Although the prevalence of anti-HCV antibodies increased with the length of hemodialysis in males without blood transfusion, it did not increase even after long-term hemodialysis (more than 5 years) in females without blood transfusion, who exhibited a rate (1.9%) similar to that of healthy blood donors in Japan. There was a significant correlation between the presence of anti-HCV antibodies and anti-HBs antibody in males without blood transfusion. In anti-HBs antibody-negative male patients without blood transfusion, the prevalence of anti-HCV antibodies was significantly lower compared with anti-HBs antibody-positive male patients without blood transfusion. There was marked difference in the prevalence rate in patients without blood transfusion among dialysis units, and there was no correlation between the prevalence and the mean period of dialysis of each dialysis unit. Although nosocomial infection with HCV appears to be related to the hemodialysis environment, the low prevalence of anti-HCV antibodies in females suggests that dialysis procedures per se may not present the risk of hepatitis C virus infection. © 1996 Wiley-Liss, Inc.     

Associations of Serum Folate and Holotranscobalamin with Cardiometabolic Risk Factors in Rural and Urban Cameroon

A low intake of fruit and vegetables and a high intake of meat are associated with higher cardiometabolic disease risk; however much prior research has relied on subjective methods for dietary assessment and focused on Western populations. We aimed to investigate the association of blood folate as an objective marker of fruit and vegetable intake and holotranscobalamin (holoTC) as a marker of animal-sourced food intake with cardiometabolic risk factors. We conducted a population-based cross-sectional study on 578 adults (mean ± SD age = 38.2 ± 8.6 years; 64% women). The primary outcome was a continuous metabolic syndrome score. The median serum folate was 12.9 (IQR: 8.6–20.5) nmol/L and the mean holoTC was 75 (SD: 34.3) pmol/L. Rural residents demonstrated higher serum folate concentrations (15.9 (9.8–25.9) nmol/L) than urban residents (11.3 (7.9–15.8) nmol/L), but lower holoTC concentrations (rural: 69.8 (32.9) pmol/L; urban: 79.8 (34.9)) pmol/L, p < 0.001 for both comparisons. There was an inverse association between serum folate and metabolic syndrome score by −0.20 in the z-score (95% CI, −0.38 to −0.02) per 10.8 (1 SD) of folate) in a model adjusted for socio-demographic factors, smoking status, alcohol intake, BMI, and physical activity. HoloTC was positively associated with the metabolic syndrome score in unadjusted analysis (0.33 (95% CI, 0.10 to 0.56)) but became non-significant (0.17 (−0.05 to 0.39)) after adjusting for socio-demographic and behavioural characteristics. In conclusion, serum folate and holoTC were associated with the metabolic syndrome score in opposite directions. The positive association between serum holoTC and the metabolic syndrome score was partly dependent on sociodemographic characteristics. These findings suggest that, based on these biomarkers reflecting dietary intakes, public health approaches promoting a higher intake of fruit and vegetables may lower cardiometabolic risk factors in this population.     

Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan

To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012‐2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2‐3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type‐specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type‐specific RCs between CIN1 and CIN2‐3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type‐specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2‐3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2‐3/AIS, and 23.7% in ICC (P < .0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01‐4.98), followed by HPV31 (2.51, 1.54‐5.24), HPV18 (2.43, 1.59‐4.32), HPV35 (1.56, 0.43‐8.36), HPV33 (1.01, 0.49‐3.31), HPV52 (0.99, 0.76‐1.33), and HPV58 (0.97, 0.75‐1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71‐2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14‐0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9‐valent vaccine contributed to 89.7% (95% CI, 88.7‐90.7) of CIN2‐3/AIS and 93.8% (95% CI, 92.4‐95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9‐valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women.     

Voice rehabilitation for laryngeal cancer after radiotherapy: a systematic review and meta-analysis

European Archives of Oto-Rhino-Laryngology - We aimed to determine whether voice rehabilitation after radiotherapy improves the quality of life (QOL), voice function, and self-rated voice function...     

Construction of Supramolecular Systems That Achieve Lifelike Functions

The Nobel Prize in Chemistry was awarded in 1987 and 2016 for research in supramolecular chemistry on the “development and use of molecules with structure-specific interactions of high selectivity” and the “design and production of molecular machines”, respectively. This confirmed the explosive development of supramolecular chemistry. In addition, attempts have been made in systems chemistry to embody the complex functions of living organisms as artificial non-equilibrium chemical systems, which have not received much attention in supramolecular chemistry. In this review, we explain recent developments in supramolecular chemistry through four categories: stimuli-responsiveness, time evolution, dissipative self-assembly, and hierarchical expression of functions. We discuss the development of non-equilibrium supramolecular systems, including the use of molecules with precisely designed properties, to achieve functions found in life as a hierarchical chemical system.