AIM: To investigate whether the pro- and anti-inflammatory cytokine gene polymorphisms, IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G, interact with smoking and drinking habits to infl...AIM: To investigate whether the pro- and anti-inflammatory cytokine gene polymorphisms, IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G, interact with smoking and drinking habits to influence infection with H pylori.METHODS: The subjects were 410 Japanese transit company employees. C-reactive protein and conventional cardiovascular risk factors were evaluated. Serum anti-H pylori antibodies were measured. The genotypes of IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G polymorphisms were determined by allelic discrimination using fluorogenic probes and a 5′nuclease assay.RESULTS: In gender- and age-adjusted logistic analyses, the subjects with TNF-857T/T had a significantly lower odds ratio (OR) for H pylori seropositivity (reference -857C/C; OR = 0.15, 95% CI: 0.03-0.59, P = 0.007). After stratification according to smoking and drinking status, among never-smokers, the subjects with IL1B-511C/T had a significantly lower OR (reference -511C/C; OR = 0.30, 95% CI: 0.10-0.90, P = 0.032). Among drinkers in the 1-5 times/wk category, the subjects with IL1B-511T/T had a significantly lower OR (reference C/C; OR = 0.38, 95% CI: 0.16-0.95, P = 0.039), and the subjects with IL1B-31C/T and T/T had a significantly higher OR (reference C/C; C/T: OR = 2.59, 95% CI, P = 0.042: 1.04-6.47; C/C: OR = 3.17, 95% CI: 1.23-8.14, P = 0.017). Among current smokers, the subjects withIL6-634C/G had a significantly higher OR (reference C/C; OR = 2.28, 95% CI: 1.13-4.58, P = 0.021). However, the interactions terms between the aforementioned genotypes and lifestyles were not statistically significant.CONCLUSION: Contrary to previous findings, the results herein suggest that the TNF-857T/T genotype may be protective against chronic infection with H pylori. Drinking and smoking habits may influence the effect of cytokine gene polymorphisms. Further studies are required to clarify the effects of the pro- and anti-inflammatory cytokine polymorphisms and gene-environmental interacti展开更多
C-type lectin receptors (CLRs) are representative pattern recognition receptors that recognize microbial polysaccharides expressed on antigen-presenting cells. In the present study, we carried out further detailed ana...C-type lectin receptors (CLRs) are representative pattern recognition receptors that recognize microbial polysaccharides expressed on antigen-presenting cells. In the present study, we carried out further detailed analysis on the involvement of Dectin-2, a CLR that senses high mannose polysaccharide, in innate immune responses induced by influenza virus hemagglutinin (HA). Treatment of HA with periodate or PNGase F induced lower interleukin (IL)-12p40 secretion by conventional dendritic cells (DCs) compared with the untreated group. In contrast, treatment with O-glycosidase did not affect cytokine production. Green fluorescent protein expression in canonical Dectin-2-transducing cells was approximately 3% - 12% following HA stimulation, except with the A/H1N1pdm09 subtype HA. This expression was markedly reduced in cells possessing mutated amino acids in the carbohydrate recognition domain of Dectin-2, especially following stimulation with HA derived from the A/H3N2 subtype. Interferon (IFN)-α production from CD11c<sup>+</sup>Siglec-H<sup>+</sup>PDCA-1<sup>+</sup> plasmacytoid DCs was significantly increased in Dectin-2 knockout mice compared with wild-type mice upon stimulation with HA except for the B/Yamagata lineage HA. These results suggested that Dectin-2 is involved in initiating inflammatory responses via mannose polysaccharide on HA. However, other mechanisms may function in the antiviral response, including the type I IFN axis.展开更多
Introduction: A scanning acoustic microscope (SAM) is an apparatus for imaging acoustic properties. This apparatus can non-invasively and rapidly evaluate the hardness of materials in the elastic region. This device s...Introduction: A scanning acoustic microscope (SAM) is an apparatus for imaging acoustic properties. This apparatus can non-invasively and rapidly evaluate the hardness of materials in the elastic region. This device shows great potential for the diagnosis of dental caries in the clinical setting. However, since the tissue elastic modulus measured using a SAM is a property of the elastic region and the Knoop hardness is a property of the plastic region, the hardness properties differ completely. Therefore, we investigated whether the acoustic impedance measured using a SAM is related to the Knoop hardness, which is used as the standard for removal of carious dentin. Method: Polished sections were prepared from 20 extracted carious wisdom teeth. The acoustic impedance and Knoop hardness were measured for each section. In addition to comparing carious and healthy dentin in SAM images, we evaluated the difference between the carious and healthy dentin in terms of the acoustic impedance and Knoop hardness. We also evaluated the correlation between the Knoop hardness and acoustic impedance. Results: The SAM images were visualized as two-dimensional color images based on the acoustic impedance values. The mean acoustic impedance of carious dentin was significantly lower than that of healthy dentin, showing a similar trend as Knoop hardness. A strong correlation was observed between the two. Discussion: The acoustic impedance values obtained through acoustic microscopy differed significantly between carious and sound dentin. Both types of dentins were visualized using two-dimensional color images. A strong correlation was observed between the acoustic impedance value, which indicates the hardness of the elastic region, and the Knoop hardness, which indicates the hardness of the plastic region. The results of the present study indicate that acoustic impedance accurately reflects the hardness of dentin.展开更多
An environmental friendly anodizing treatment (Anomag) from a phosphate-based so lution without heavy metals on AZ91D magnesium alloy was studied. The characteri stics of the coatings, such as structure, composition a...An environmental friendly anodizing treatment (Anomag) from a phosphate-based so lution without heavy metals on AZ91D magnesium alloy was studied. The characteri stics of the coatings, such as structure, composition and corrosion resistance w ere investigated. The effects of this anodizing treatment on the mechanical prop erties were examined. X-ray diffraction (XRD) analysis revealed that the structu re of the coatings is amorphous or glassy. In salt spray tests coatings with an average thickness of 10μm had an anticorrosive performance of over 1000 hours. Fatigue tests revealed that anodizing onto AZ91D magnesium alloy does not affect the fatigue strength. These results demonstrate the utility of this anodizing t reatment on magnesium alloy for application as a structural material, such as in the automotive field.展开更多
The fixing of a silane coupling agent to Zn-Ni-silica(SiO_(2))composite coatings was studied for the purpose of developing a coating process as an alternative to chromating.The corrosion resistance of Zn-Ni-silica com...The fixing of a silane coupling agent to Zn-Ni-silica(SiO_(2))composite coatings was studied for the purpose of developing a coating process as an alternative to chromating.The corrosion resistance of Zn-Ni-silica composite coatings was rem arkably improved by the silica nanoparticles in the composite,which were disper sed in the surface of this film.The silane coupling agent formed chemical bonds with the inorganic silica particles during the silane coupling treatment on the se composite coatings.The treatment suppressed the formation of white corrosion products to the same extent as chromating,as measured in salt spray tests.It is concluded that treating Zn-Ni-silica composite coatings with silane coupling agents is a viable alternative technique to chromating.展开更多
Genetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Meiosis is unique to germ cells and essential for reproduction. The synaptonemal complex is a critical component for ch...Genetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Meiosis is unique to germ cells and essential for reproduction. The synaptonemal complex is a critical component for chromosome pairing, segregation and recombination. Hormadl is essential for mammalian gametogenesis as knockout male mice are infertile. Hormadl-deficient testes exhibit meiotic arrest in the early pachytene stage and synaptonema! complexes cannot be visualized. To analyze the hypothesis that the human HORMAD1 gene defects are associated with human azoospermia caused by meiotic arrest, mutational analysis was performed in all coding regions by direct sequence analysis of 30 Japanese men diagnosed with azoospermia resulting from meiotic arrest. By the sequence analysis, three polymorphism sites, Single Nucleotide Polymorphism 1 （c. 163A〉G）, SNP2 （c. 501T〉G） and SNP3 （c. 918C〉T）, were found in exons 3, 8 and 10. The 30 patients with azoospermia and 80 normal pregnancy-proven, fertile men were analyzed for HORMAD1 polymorphisms. Both SNP1 and SNP2 were associated with human azoospermia caused by complete early meiotic arrest （P〈0.0S）. We suggest that the HORMAD1 has an essential meiotic function in human spermatogenesis.展开更多
Cardiac amyloidosis is an infiltrative and restrictive cardiomyopathy caused by the extracellular deposition of amyloid fib-rils within the heart as systemic amyloidosis,lead-ing to heart failure,reduced quality of li...Cardiac amyloidosis is an infiltrative and restrictive cardiomyopathy caused by the extracellular deposition of amyloid fib-rils within the heart as systemic amyloidosis,lead-ing to heart failure,reduced quality of life,and death.[1]There are two major amyloid fibril proteins that af-fect the heart:amyloid immunoglobulin light chain(AL)and amyloid transthyretin(ATTR).The latter is further subdivided into wild-type ATTR and variant types based on the presence of a mutation in the transthyretin gene.展开更多
Pleomorphic adenoma is the most common benign parotid gland tumor. Although its local recurrence rate is known to be high, the recurrence extending to the cervical region is rare. Here we report a case of a young fema...Pleomorphic adenoma is the most common benign parotid gland tumor. Although its local recurrence rate is known to be high, the recurrence extending to the cervical region is rare. Here we report a case of a young female (25 years old) with pleomorphic adenoma of the parotid gland which showed multiple recurrences through facial to cervical regions over a span of eight years. We also discuss how this benign tumor with a high recurrence rate has been treated in other cases, and how it should be treated.展开更多
BACKGROUND Metastasis occurs as a late event in the natural history of hepatocellular carcinoma(HCC),and most patients die of liver failure attributed to the tumor supplanting the liver.Conversely,the brain is a less ...BACKGROUND Metastasis occurs as a late event in the natural history of hepatocellular carcinoma(HCC),and most patients die of liver failure attributed to the tumor supplanting the liver.Conversely,the brain is a less common metastatic site.CASE SUMMARY We describe a rare case of hepatitis C virus-related multiple HCC metastasizing to the cavernous sinus,Meckel’s cave,and the petrous bone involving multiple cranial nerves in an 82-year-old woman.At admission imaging studies including Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(MRI)revealed multiple HCC nodules in both right and left lobes.Ultrasound guided biopsy of the left lobe revealed moderately differentiated HCC.Molecular targeted therapy with Lenvatinib(8 mg/d for 94 d,per os)and Ramucirumab(340 mg/d and 320 mg/d,two times by intravenous injection)were administered for 4 mo,resulting in progression of the disease.Three months after the start of molecular target therapy,the patient presented with symptoms of hyperalgesia of the right face and limited abduction of the right eye,indicating disturbances in the right trigeminal and abducens nerves.Brain MRI disclosed a mass involving the cavernous sinus,Meckel’s cave and the petrous bone.Contrast-enhanced MRI with gadolinium-chelated contrast medium revealed a well-defined mass with abnormal enhancement around the right cavernous sinus and the right Meckel’s cave.CONCLUSION The diagnosis of metastatic HCC to the cavernous sinus,Meckel’s cave,and the petrous bone was made based on neurological findings and imaging studies including MRI,but not on histological examinations.Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.展开更多
Dear Editor,Approximately 20% of men with nonobstructive azoospermia （NOA） are diagnosed with infertility caused by genetic defects.1 These include chromosomal abnormalities, Y-chromosome microdeletions, and several...Dear Editor,Approximately 20% of men with nonobstructive azoospermia （NOA） are diagnosed with infertility caused by genetic defects.1 These include chromosomal abnormalities, Y-chromosome microdeletions, and several specific gene mutations/deletions, such as in DAZ, RBMY, USP9Y, SYCP3, HSF2, PLK4, and TEX11.1,2 Several histones have been detected in mammalian testes, and testis-specific variants are specifically and highly expressed during spermatogenesis^3.展开更多
Severe fever with thrombocytopenia syndrome(SFTS),a tick-borne infectious disease with high mortality,is diagnosed by the serological testing of serum samples from patients in the acute and convalescent phases and/or ...Severe fever with thrombocytopenia syndrome(SFTS),a tick-borne infectious disease with high mortality,is diagnosed by the serological testing of serum samples from patients in the acute and convalescent phases and/or by direct detection of the SFTS virus(SFTSV).Conventionally,heat and UV treatments have been used to inactivate the viruses present in serum samples before performing the serological assays.Here,we examined the inactivation conditions optimal for SFTSV-containing serum samples to ensure the safety of laboratory workers while maintaining the accuracy of serological assay results simultaneously.Heating human serum samples spiked with SFTSV to 60C for 30 min or exposing them to UV irradiation for 30 min,reduced the infectious virus titer below the limit of detection.SFTSV in sera from patients in the acute phase of SFTS was completely inactivated by heating to 60C for 30 min,followed by UV irradiation for 10 min.This inactivation procedure had minimal impact on the performance of SFTSV antibody detection tests.The data provided herein can serve as a guide for laboratory workers and researchers working with SFTS serological tests.展开更多
Aim: Excessive microglial inflammation has emerged as a key player in mediating the effects of aging and neurodegeneration on brain dysfunction. Thus, there is great interest in discovering transcriptional repressors ...Aim: Excessive microglial inflammation has emerged as a key player in mediating the effects of aging and neurodegeneration on brain dysfunction. Thus, there is great interest in discovering transcriptional repressors that can control this process. We aimed to examine whether Phf15 - one of the top differentially expressed genes in microglia during aging in humans - could regulate transcription of proinflammatory mediators in microglia. Methods: Real-time quantitative PCR was used to assess Phf15 mRNA expression in mouse brain during aging. Loss-of-function [short hairpin RNA (shRNA) -mediated knockdown (KD) and CRISPR/Cas9-mediated knockout (KO) of Phf15] and gain-of-function [retroviral overexpression (OE) of murine Phf15 cDNA] studies in a murine microglial cell line (SIM-A9) followed by immune activation with lipopolysaccharide were used to determine the effect of Phf15 on proinflammatory factor (Tnfα , IL-1β , and Nos2) mRNA expression. RNA sequencing was used to determine global transcriptional changes afterPhf15 knockout under basal conditions and after lipopolysaccharide stimulation. Results:Phf15 expression increases in mouse brain during aging, similar to humans. KD, KO, and OE studies determined that Phf15 represses mRNA expression levels of proinflammatory mediators such as Tnfα , IL-1β , and Nos2 . Global transcriptional changes after Phf15 KO showed that Phf15 specifically represses genes related to the antiviral (type I interferon) response and cytokine production in microglia. Conclusion: We provide the first evidence thatPhf15 is an important transcriptional repressor of microglial inflammation, regulating the antiviral response and proinflammatory cytokine production. Importantly, Phf15 regulates both basal and signal-dependent activation and controls the magnitude and duration of the microglial inflammatory response.展开更多
Steady and useful culture for chondrocytes is essential for cartilage regenerative medicine. However, in conventional plate culture, the chondrocytes become dedifferentiated and lose their ability to make cartilage ma...Steady and useful culture for chondrocytes is essential for cartilage regenerative medicine. However, in conventional plate culture, the chondrocytes become dedifferentiated and lose their ability to make cartilage matrices. Three-dimensional culture mimicking the physiological environment in native chondrocytes is useful to maintain the chondrocyte properties during the proliferation culture. However, the three-dimensional culture is practically a hard task due to difficult harvest of the cells. Thus, we attempted to apply porous materials, hollow fibers for the three-dimensional culture, and developed their module to realize the effective harvest of the cells. Polyethersulfone-based hollow fibers, whose safety and cell affinity were confirmed by the experiment of the coculture with human chondrocytes, were collected to fabricate a module. The hollow fiber module was installed with screw ends, and enabled the easy removal of chondrocytes from the inner unit. Cultured human chondrocytes embedded within collagen hydrogel were put into the outer lumen of the hollow fiber module, while chondrocyte prolfieration medium was perfused through the inner lumen at 0 to 30 mL/min. After 2 weeks’ culture, the flow rate of 3 to 10 mL/min effectively supported the chondrocyte proliferation. Then, long-term culture using the hollow fiber module at flow rate of 5 mL/min was performed, revealing that the cell growth in this module at 3 weeks was approximately twice larger than that in static culture. The numbers of viable cells could be maintained by week 7. The hollow fiber module installed with screw ends can effectively culture and harvest the chondrocytes.展开更多
Aims: Dilated cardiomyopathy often shows left ventricular systolic dysfunction, although histologically it always exhibits non-specific abnormality. We hypothesized that myocyte sound speed might be altered due to inc...Aims: Dilated cardiomyopathy often shows left ventricular systolic dysfunction, although histologically it always exhibits non-specific abnormality. We hypothesized that myocyte sound speed might be altered due to incomplete protein accumulation in cells. Methods and Results: Ninety eight biopsied samples were obtained from 49 patients comprising 43 with clinical dilated cardiomyopathy and 6 with hypertrophic cardiomyopathy. Sound speed was evaluated in deparaffinized 10 μm thick sections using an acoustic microscope (frequency range: 50 - 105 MHz). Conventional histology revealed 7 cases of persistent myocarditis derived from clinical dilated cardio- myopathy samples. Histology of the remaining dilated cardiomyopathy patients indicated non-specific abnormality. All hypertrophic cardiomyopathy cases exhibited myocardial disarray. Ten normal autopsied hearts were compared as controls. The sound speed of controls was 1627 ± 30m/sec. The sound speed in dilated cardiomyopathy samples (1700 ±51m/sec) was 1.045-fold faster compared to controls. The sound speed in hypertrophic cardiomyopathy samples (1734 ±51m/sec, 1.066-fold compared to controls) was faster than that of the myocarditis group (1672 ±30m/sec, 1.028-fold) (P = 0.0218). Furtheremore, desmin expression was evaluated as extent of emergence (grading 0 - 4). The desmin expression score in hypertrophic cardiomyopathy samples (2.7 ± 0.8) was significantly higher than in other groups (dilated 2.0 ± 1.4, myocarditis 1.6 ± 1.5 vs., controls 0, P ≤ 0.0001, 0.0001, 0.0129, respectively). Conclusion: Cardio-myopathy enhanced the sound speed, which correlated with the elasticity of myocytes, following the impaired compliance of left ventricle, despite the absence of histological changes. The elevation of sound speed of myocytes may be linked to cytoskeletal changes. Myocyte sound speed may be a new diagnostic tool for diagnosis of idiopathic cardiomyopathy independently of conventional histological diagnosis.展开更多
基金a Grant-in-Aid for Young Scientists from the Ministry of Education,Culture,Sports,Science and Technology of Japana Grant-in-Aid for Scientific Research from the Ministry of Health,Labour and Welfare of Japan
文摘AIM: To investigate whether the pro- and anti-inflammatory cytokine gene polymorphisms, IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G, interact with smoking and drinking habits to influence infection with H pylori.METHODS: The subjects were 410 Japanese transit company employees. C-reactive protein and conventional cardiovascular risk factors were evaluated. Serum anti-H pylori antibodies were measured. The genotypes of IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G polymorphisms were determined by allelic discrimination using fluorogenic probes and a 5′nuclease assay.RESULTS: In gender- and age-adjusted logistic analyses, the subjects with TNF-857T/T had a significantly lower odds ratio (OR) for H pylori seropositivity (reference -857C/C; OR = 0.15, 95% CI: 0.03-0.59, P = 0.007). After stratification according to smoking and drinking status, among never-smokers, the subjects with IL1B-511C/T had a significantly lower OR (reference -511C/C; OR = 0.30, 95% CI: 0.10-0.90, P = 0.032). Among drinkers in the 1-5 times/wk category, the subjects with IL1B-511T/T had a significantly lower OR (reference C/C; OR = 0.38, 95% CI: 0.16-0.95, P = 0.039), and the subjects with IL1B-31C/T and T/T had a significantly higher OR (reference C/C; C/T: OR = 2.59, 95% CI, P = 0.042: 1.04-6.47; C/C: OR = 3.17, 95% CI: 1.23-8.14, P = 0.017). Among current smokers, the subjects withIL6-634C/G had a significantly higher OR (reference C/C; OR = 2.28, 95% CI: 1.13-4.58, P = 0.021). However, the interactions terms between the aforementioned genotypes and lifestyles were not statistically significant.CONCLUSION: Contrary to previous findings, the results herein suggest that the TNF-857T/T genotype may be protective against chronic infection with H pylori. Drinking and smoking habits may influence the effect of cytokine gene polymorphisms. Further studies are required to clarify the effects of the pro- and anti-inflammatory cytokine polymorphisms and gene-environmental interacti
文摘C-type lectin receptors (CLRs) are representative pattern recognition receptors that recognize microbial polysaccharides expressed on antigen-presenting cells. In the present study, we carried out further detailed analysis on the involvement of Dectin-2, a CLR that senses high mannose polysaccharide, in innate immune responses induced by influenza virus hemagglutinin (HA). Treatment of HA with periodate or PNGase F induced lower interleukin (IL)-12p40 secretion by conventional dendritic cells (DCs) compared with the untreated group. In contrast, treatment with O-glycosidase did not affect cytokine production. Green fluorescent protein expression in canonical Dectin-2-transducing cells was approximately 3% - 12% following HA stimulation, except with the A/H1N1pdm09 subtype HA. This expression was markedly reduced in cells possessing mutated amino acids in the carbohydrate recognition domain of Dectin-2, especially following stimulation with HA derived from the A/H3N2 subtype. Interferon (IFN)-α production from CD11c<sup>+</sup>Siglec-H<sup>+</sup>PDCA-1<sup>+</sup> plasmacytoid DCs was significantly increased in Dectin-2 knockout mice compared with wild-type mice upon stimulation with HA except for the B/Yamagata lineage HA. These results suggested that Dectin-2 is involved in initiating inflammatory responses via mannose polysaccharide on HA. However, other mechanisms may function in the antiviral response, including the type I IFN axis.
文摘Introduction: A scanning acoustic microscope (SAM) is an apparatus for imaging acoustic properties. This apparatus can non-invasively and rapidly evaluate the hardness of materials in the elastic region. This device shows great potential for the diagnosis of dental caries in the clinical setting. However, since the tissue elastic modulus measured using a SAM is a property of the elastic region and the Knoop hardness is a property of the plastic region, the hardness properties differ completely. Therefore, we investigated whether the acoustic impedance measured using a SAM is related to the Knoop hardness, which is used as the standard for removal of carious dentin. Method: Polished sections were prepared from 20 extracted carious wisdom teeth. The acoustic impedance and Knoop hardness were measured for each section. In addition to comparing carious and healthy dentin in SAM images, we evaluated the difference between the carious and healthy dentin in terms of the acoustic impedance and Knoop hardness. We also evaluated the correlation between the Knoop hardness and acoustic impedance. Results: The SAM images were visualized as two-dimensional color images based on the acoustic impedance values. The mean acoustic impedance of carious dentin was significantly lower than that of healthy dentin, showing a similar trend as Knoop hardness. A strong correlation was observed between the two. Discussion: The acoustic impedance values obtained through acoustic microscopy differed significantly between carious and sound dentin. Both types of dentins were visualized using two-dimensional color images. A strong correlation was observed between the acoustic impedance value, which indicates the hardness of the elastic region, and the Knoop hardness, which indicates the hardness of the plastic region. The results of the present study indicate that acoustic impedance accurately reflects the hardness of dentin.
文摘An environmental friendly anodizing treatment (Anomag) from a phosphate-based so lution without heavy metals on AZ91D magnesium alloy was studied. The characteri stics of the coatings, such as structure, composition and corrosion resistance w ere investigated. The effects of this anodizing treatment on the mechanical prop erties were examined. X-ray diffraction (XRD) analysis revealed that the structu re of the coatings is amorphous or glassy. In salt spray tests coatings with an average thickness of 10μm had an anticorrosive performance of over 1000 hours. Fatigue tests revealed that anodizing onto AZ91D magnesium alloy does not affect the fatigue strength. These results demonstrate the utility of this anodizing t reatment on magnesium alloy for application as a structural material, such as in the automotive field.
文摘The fixing of a silane coupling agent to Zn-Ni-silica(SiO_(2))composite coatings was studied for the purpose of developing a coating process as an alternative to chromating.The corrosion resistance of Zn-Ni-silica composite coatings was rem arkably improved by the silica nanoparticles in the composite,which were disper sed in the surface of this film.The silane coupling agent formed chemical bonds with the inorganic silica particles during the silane coupling treatment on the se composite coatings.The treatment suppressed the formation of white corrosion products to the same extent as chromating,as measured in salt spray tests.It is concluded that treating Zn-Ni-silica composite coatings with silane coupling agents is a viable alternative technique to chromating.
文摘Genetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Meiosis is unique to germ cells and essential for reproduction. The synaptonemal complex is a critical component for chromosome pairing, segregation and recombination. Hormadl is essential for mammalian gametogenesis as knockout male mice are infertile. Hormadl-deficient testes exhibit meiotic arrest in the early pachytene stage and synaptonema! complexes cannot be visualized. To analyze the hypothesis that the human HORMAD1 gene defects are associated with human azoospermia caused by meiotic arrest, mutational analysis was performed in all coding regions by direct sequence analysis of 30 Japanese men diagnosed with azoospermia resulting from meiotic arrest. By the sequence analysis, three polymorphism sites, Single Nucleotide Polymorphism 1 （c. 163A〉G）, SNP2 （c. 501T〉G） and SNP3 （c. 918C〉T）, were found in exons 3, 8 and 10. The 30 patients with azoospermia and 80 normal pregnancy-proven, fertile men were analyzed for HORMAD1 polymorphisms. Both SNP1 and SNP2 were associated with human azoospermia caused by complete early meiotic arrest （P〈0.0S）. We suggest that the HORMAD1 has an essential meiotic function in human spermatogenesis.
文摘Cardiac amyloidosis is an infiltrative and restrictive cardiomyopathy caused by the extracellular deposition of amyloid fib-rils within the heart as systemic amyloidosis,lead-ing to heart failure,reduced quality of life,and death.[1]There are two major amyloid fibril proteins that af-fect the heart:amyloid immunoglobulin light chain(AL)and amyloid transthyretin(ATTR).The latter is further subdivided into wild-type ATTR and variant types based on the presence of a mutation in the transthyretin gene.
文摘Pleomorphic adenoma is the most common benign parotid gland tumor. Although its local recurrence rate is known to be high, the recurrence extending to the cervical region is rare. Here we report a case of a young female (25 years old) with pleomorphic adenoma of the parotid gland which showed multiple recurrences through facial to cervical regions over a span of eight years. We also discuss how this benign tumor with a high recurrence rate has been treated in other cases, and how it should be treated.
文摘BACKGROUND Metastasis occurs as a late event in the natural history of hepatocellular carcinoma(HCC),and most patients die of liver failure attributed to the tumor supplanting the liver.Conversely,the brain is a less common metastatic site.CASE SUMMARY We describe a rare case of hepatitis C virus-related multiple HCC metastasizing to the cavernous sinus,Meckel’s cave,and the petrous bone involving multiple cranial nerves in an 82-year-old woman.At admission imaging studies including Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(MRI)revealed multiple HCC nodules in both right and left lobes.Ultrasound guided biopsy of the left lobe revealed moderately differentiated HCC.Molecular targeted therapy with Lenvatinib(8 mg/d for 94 d,per os)and Ramucirumab(340 mg/d and 320 mg/d,two times by intravenous injection)were administered for 4 mo,resulting in progression of the disease.Three months after the start of molecular target therapy,the patient presented with symptoms of hyperalgesia of the right face and limited abduction of the right eye,indicating disturbances in the right trigeminal and abducens nerves.Brain MRI disclosed a mass involving the cavernous sinus,Meckel’s cave and the petrous bone.Contrast-enhanced MRI with gadolinium-chelated contrast medium revealed a well-defined mass with abnormal enhancement around the right cavernous sinus and the right Meckel’s cave.CONCLUSION The diagnosis of metastatic HCC to the cavernous sinus,Meckel’s cave,and the petrous bone was made based on neurological findings and imaging studies including MRI,but not on histological examinations.Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.
文摘Dear Editor,Approximately 20% of men with nonobstructive azoospermia （NOA） are diagnosed with infertility caused by genetic defects.1 These include chromosomal abnormalities, Y-chromosome microdeletions, and several specific gene mutations/deletions, such as in DAZ, RBMY, USP9Y, SYCP3, HSF2, PLK4, and TEX11.1,2 Several histones have been detected in mammalian testes, and testis-specific variants are specifically and highly expressed during spermatogenesis^3.
基金This work was supported in part by a grant from the Japan Agency for Medical Research and Development(AMED)(#JP19fk0108070,JP19fk0108081,and JP19fk0108072).
文摘Severe fever with thrombocytopenia syndrome(SFTS),a tick-borne infectious disease with high mortality,is diagnosed by the serological testing of serum samples from patients in the acute and convalescent phases and/or by direct detection of the SFTS virus(SFTSV).Conventionally,heat and UV treatments have been used to inactivate the viruses present in serum samples before performing the serological assays.Here,we examined the inactivation conditions optimal for SFTSV-containing serum samples to ensure the safety of laboratory workers while maintaining the accuracy of serological assay results simultaneously.Heating human serum samples spiked with SFTSV to 60C for 30 min or exposing them to UV irradiation for 30 min,reduced the infectious virus titer below the limit of detection.SFTSV in sera from patients in the acute phase of SFTS was completely inactivated by heating to 60C for 30 min,followed by UV irradiation for 10 min.This inactivation procedure had minimal impact on the performance of SFTSV antibody detection tests.The data provided herein can serve as a guide for laboratory workers and researchers working with SFTS serological tests.
基金This work was supported by the Berkeley Fellowship to S.E.M.,ADA Postdoctoral fellowship to G.A.T.,NSF GRFP to M.K.P.,and R01HD092093 and Pew Scholarship to K.S
文摘Aim: Excessive microglial inflammation has emerged as a key player in mediating the effects of aging and neurodegeneration on brain dysfunction. Thus, there is great interest in discovering transcriptional repressors that can control this process. We aimed to examine whether Phf15 - one of the top differentially expressed genes in microglia during aging in humans - could regulate transcription of proinflammatory mediators in microglia. Methods: Real-time quantitative PCR was used to assess Phf15 mRNA expression in mouse brain during aging. Loss-of-function [short hairpin RNA (shRNA) -mediated knockdown (KD) and CRISPR/Cas9-mediated knockout (KO) of Phf15] and gain-of-function [retroviral overexpression (OE) of murine Phf15 cDNA] studies in a murine microglial cell line (SIM-A9) followed by immune activation with lipopolysaccharide were used to determine the effect of Phf15 on proinflammatory factor (Tnfα , IL-1β , and Nos2) mRNA expression. RNA sequencing was used to determine global transcriptional changes afterPhf15 knockout under basal conditions and after lipopolysaccharide stimulation. Results:Phf15 expression increases in mouse brain during aging, similar to humans. KD, KO, and OE studies determined that Phf15 represses mRNA expression levels of proinflammatory mediators such as Tnfα , IL-1β , and Nos2 . Global transcriptional changes after Phf15 KO showed that Phf15 specifically represses genes related to the antiviral (type I interferon) response and cytokine production in microglia. Conclusion: We provide the first evidence thatPhf15 is an important transcriptional repressor of microglial inflammation, regulating the antiviral response and proinflammatory cytokine production. Importantly, Phf15 regulates both basal and signal-dependent activation and controls the magnitude and duration of the microglial inflammatory response.
文摘Steady and useful culture for chondrocytes is essential for cartilage regenerative medicine. However, in conventional plate culture, the chondrocytes become dedifferentiated and lose their ability to make cartilage matrices. Three-dimensional culture mimicking the physiological environment in native chondrocytes is useful to maintain the chondrocyte properties during the proliferation culture. However, the three-dimensional culture is practically a hard task due to difficult harvest of the cells. Thus, we attempted to apply porous materials, hollow fibers for the three-dimensional culture, and developed their module to realize the effective harvest of the cells. Polyethersulfone-based hollow fibers, whose safety and cell affinity were confirmed by the experiment of the coculture with human chondrocytes, were collected to fabricate a module. The hollow fiber module was installed with screw ends, and enabled the easy removal of chondrocytes from the inner unit. Cultured human chondrocytes embedded within collagen hydrogel were put into the outer lumen of the hollow fiber module, while chondrocyte prolfieration medium was perfused through the inner lumen at 0 to 30 mL/min. After 2 weeks’ culture, the flow rate of 3 to 10 mL/min effectively supported the chondrocyte proliferation. Then, long-term culture using the hollow fiber module at flow rate of 5 mL/min was performed, revealing that the cell growth in this module at 3 weeks was approximately twice larger than that in static culture. The numbers of viable cells could be maintained by week 7. The hollow fiber module installed with screw ends can effectively culture and harvest the chondrocytes.
文摘Aims: Dilated cardiomyopathy often shows left ventricular systolic dysfunction, although histologically it always exhibits non-specific abnormality. We hypothesized that myocyte sound speed might be altered due to incomplete protein accumulation in cells. Methods and Results: Ninety eight biopsied samples were obtained from 49 patients comprising 43 with clinical dilated cardiomyopathy and 6 with hypertrophic cardiomyopathy. Sound speed was evaluated in deparaffinized 10 μm thick sections using an acoustic microscope (frequency range: 50 - 105 MHz). Conventional histology revealed 7 cases of persistent myocarditis derived from clinical dilated cardio- myopathy samples. Histology of the remaining dilated cardiomyopathy patients indicated non-specific abnormality. All hypertrophic cardiomyopathy cases exhibited myocardial disarray. Ten normal autopsied hearts were compared as controls. The sound speed of controls was 1627 ± 30m/sec. The sound speed in dilated cardiomyopathy samples (1700 ±51m/sec) was 1.045-fold faster compared to controls. The sound speed in hypertrophic cardiomyopathy samples (1734 ±51m/sec, 1.066-fold compared to controls) was faster than that of the myocarditis group (1672 ±30m/sec, 1.028-fold) (P = 0.0218). Furtheremore, desmin expression was evaluated as extent of emergence (grading 0 - 4). The desmin expression score in hypertrophic cardiomyopathy samples (2.7 ± 0.8) was significantly higher than in other groups (dilated 2.0 ± 1.4, myocarditis 1.6 ± 1.5 vs., controls 0, P ≤ 0.0001, 0.0001, 0.0129, respectively). Conclusion: Cardio-myopathy enhanced the sound speed, which correlated with the elasticity of myocytes, following the impaired compliance of left ventricle, despite the absence of histological changes. The elevation of sound speed of myocytes may be linked to cytoskeletal changes. Myocyte sound speed may be a new diagnostic tool for diagnosis of idiopathic cardiomyopathy independently of conventional histological diagnosis.
