ABSTRACT
Multilayer diffraction gratings are designed to improve the detection limit and sensitivity of soft x-ray flat-field spectrographs in the region of 300-1000 eV, placing emphasis on Fe-L (705 eV), Cu-L (930 eV), and Zn-L (1012 eV) emissions. For this purpose, spectral flux was used as the performance index, which is proportional to the amount of optical flux incident into a detector and correlated with detection sensitivity. A super-mirror-type W/B4C multilayer coating [Koike et al., Rev.Sci. Instrum. 94, 045109 (2023)] was employed to improve diffraction efficiency in a wide energy region. The unique feature of the multilayer structure is that the average refractive index and the period length of W/B4C layer pairs are increased from the bottom to top layers. In addition, the incidence angle was reduced to 86.03° from 88.65° and the nominal groove density was increased to 3200 lines/mm from 2400 lines/mm of our previous design, to improve spectral flux while maintaining dispersion and spectral resolution. A holographic varied-line-spacing spherical grating and a soft x-ray flat-field spectrograph were designed, using the aspherical-wavefront-recording method, assuming the nominal grating constant and incident angle described above. The numerical simulation results showed that the spectrograph employing the newly designed grating with the W/B4C multilayer indicated 3.2-8.2 times higher spectral flux compared with those using the previously designed grating while keeping the same spectral resolution.
ABSTRACT
A soft x-ray varied-line-spacing (VLS) laminar-type spherical grating with a super-mirror-type (SMT) multilayer was designed for a soft x-ray high resolution flat-field spectrograph in a region of 2-4 keV. The effective groove density of the designed VLS grating is 3200 lines/mm, and the local groove density varies from 2700 to 3866 lines/mm. The geometrical imaging property was evaluated by numerical calculations. The resolving power estimated by means of ray tracing was up to â¼103. For the evaluation of diffraction efficiency, the SMT multilayer structure designed for 3200 lines/mm in our previous work, Koike et al., Rev. Sci. Instrum. 94, 045109 (2023), was employed, and the numerical calculation was performed considering the local groove density of VLS grooves and the local incidence angle being affected by the curvature of the spherical surface and the geometrical relation between the source and incidence point on the grating. The results showed that the SMT multilayer-coated grating exhibited about an order of magnitude higher diffraction efficiency compared with an Au-coated grating.
ABSTRACT
Soft x-ray diffraction gratings coated with a supermirror-type multilayer were designed to enhance diffraction efficiency in the energy range of 2-4 keV by means of numerical calculations. The optimized groove depth and incidence angle are 2.05 nm and 88.65°, respectively, for the grating having a groove density of 3200 grooves/mm. Regarding the multilayer structure, the optimum number of B4C/W layers pair was 11 and the thickness of B4C was increased from bottom to top, while that of W was kept constant. The replacement of the top layer of W by either Co, Cr, or Ni was an effective means of obtaining uniform diffraction efficiency. In the region of 2-4 keV, the calculated diffraction efficiency of the designed gratings was up to â¼5.3%, on average, and almost eight times larger than that of â¼0.7% of an Au coated grating.
ABSTRACT
Laminar-type spherical diffraction gratings overcoated with carbon-based materials were designed, fabricated, and evaluated for the purpose of enhancing the analytical sensitivity of the flat-field spectrograph in a vacuum ultraviolet region of 35-110 eV. As the design benchmark for numerical calculations, diffraction efficiency (DE) and spectral flux, which are defined by the product of the DE and numerical aperture and correlate with the analytical sensitivity of the spectrograph, were used. To simplify the feasibility study on the overcoating effects, we assumed a laminar-type grating having a grating constant of 1/1000 mm and coated with a Au layer of 30.0 nm thickness and an incidence angle of 84.0°. The optimized groove depth and duty ratio were 30.0 nm and 0.3, respectively. In addition, the optimum thicknesses of the overcoating layer were 44, 46, 24, and 30 nm for B4C, C, diamond-like-carbon, and SiC, respectively. Based on these results, we have fabricated a varied-line-spacing holographic grating overcoated with B4C with a thickness of 47 nm. For the experimental evaluation, we used the light source of Mg-L and Al-L emissions excited by the electron beam generated from an electron microscope, an objective flat-field spectrograph, and a CCD imaging detector. The experimental results showed that the spectrograph employing a new grating overcoated with the B4C layer indicated almost the same spectral resolution and 2.9-4.2 times higher analytical sensitivity compared with those obtained with a previously designed Au-coated grating having a grating constant of 1/1200 mm and used at an incidence of 86.0°.
ABSTRACT
BACKGROUND: Poor oral health can lead to poor general health. We hypothesized that poor oral health might be a factor that attenuates the effect of rehabilitation in older patients with fractures. OBJECTIVES: This study aimed to evaluate the relationship between oral health in elderly patients with fractures and improvement in activities of daily living (ADL) through rehabilitation. In addition, we assessed factors associated with ADL improvement among older patients with fractures. METHODS: This case-control study was conducted at a rehabilitation hospital among 178 men aged ≥65 years who underwent fracture rehabilitation. Patients were divided into two groups based on the oral health assessment tool (OHAT) score on admission (≥4 and <4). Analysis of comparison between the two groups and multivariate linear regression analyses were performed, with respect to functional independence measure (FIM) gain during rehabilitation. RESULTS: FIM gain was significantly lower in the group with OHAT score ≥4 (26.2±17.5) than that in group with OHAT score <4 (31.1±16.1, p=0.044). There were also significant differences between the two groups in body mass index values, Mini Nutritional Assessment Short Form (MNA-SF) scores, and fracture types. OHAT score on admission was significantly associated with FIM gain during hospitalization (coefficient: 6.350, 95% confidence interval: 1.043-11.658, p=0.019). FIM on admission, Mini-Mental State Examination score, and period of rehabilitation were significantly associated with FIM gain. CONCLUSIONS: We demonstrated that the group with poor oral health had lesser ADL improvement than the group with good oral health. In addition, oral health and period of rehabilitation were independent factors that significantly affected ADL improvements. Older patients with poor oral health should be encouraged to undergo further rehabilitation, and to not refrain from exercise because of old age and fractures.
Subject(s)
Activities of Daily Living , Hip Fractures , Aged , Case-Control Studies , Hip Fractures/rehabilitation , Hospitalization , Humans , Male , Oral Health , Retrospective Studies , Treatment OutcomeABSTRACT
Despite improvements in surgical techniques, perioperative management, and multidisciplinary therapy, treatment outcomes of patients with esophageal squamous cell carcinoma (ESCC) remain poor. Therefore, development of novel molecular biomarkers, which either predict patient survival or become therapeutic targets, is urgently required. In the present study, to facilitate early detection of ESCC and predict its clinical course, we investigated the relationship of the serum level of melanoma-associated antigen (MAGE)-D4 to patients' clinicopathological characteristics. Using quantitative real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assays, we determined the levels of MAGE-D4 mRNA and protein in cell lysates and conditioned medium of cultures, respectively, of nine ESCC cell lines. Further, we determined MAGE-D4 levels in serum samples collected from 44 patients with ESCC who underwent radical esophagectomy without neoadjuvant therapy as well as from 40 healthy volunteers. Samples of conditioned medium and cell lysates contained comparable levels of MAGE-D4 that correlated closely with the levels of MAGE-D4 mRNA. Preoperative MAGE-D4 levels in the sera of 44 patients with ESCC, which varied from 0 to 2,354 pg/mL (314 ± 505 pg/mL, mean ± standard deviation), were significantly higher compared with those of healthy volunteers. By setting the cutoff at the highest value for healthy volunteers (50 pg/mL), the MAGE-D4-positive group of patients was more likely to have shorter disease-specific and disease-free survival compared with those of the MAGE-D4-negative group, although the differences were not statistically significant. Our results indicate that the elevation of preoperative serum MAGE-D4 levels in some patients with ESCC was possibly caused by excess production of MAGE-D4 by tumor cells followed by its release into the circulation. Clinical implications of serum MAGE-D4 levels should be validated in a large population of patients with ESCC.
Subject(s)
Antigens, Neoplasm/blood , Biomarkers, Tumor/blood , Carcinoma, Squamous Cell/blood , Esophageal Neoplasms/blood , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/genetics , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/surgery , Case-Control Studies , Cell Line, Tumor , Disease-Free Survival , Enzyme-Linked Immunosorbent Assay , Esophageal Neoplasms/genetics , Esophageal Neoplasms/surgery , Esophageal Squamous Cell Carcinoma , Esophagectomy , Female , Humans , Male , Middle Aged , Prognosis , RNA, Messenger/blood , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Historically, total pharyngolaryngectomy with total esophagectomy has been the standard radical surgical treatment for synchronous cancer of the thoracoabdominal esophagus and pharyngolaryngeal region, and for cancer of the cervical esophagus that has invaded as far as the thoracic esophagus. Although definitive chemoradiotherapy that enables preservation of the larynx has often been the first choice of treatment for cancers involving the cervical esophagus, total pharyngolaryngectomy with total esophagectomy is required as a salvage therapy for cases involving failure of complete remission or locoregional recurrence after chemoradiotherapy. However, salvage esophageal surgery after definitive high-dose chemoradiotherapy is generally associated with high morbidity and mortality. The aim of this study was to examine the short-term outcome of salvage total pharyngolaryngectomy with total esophagectomy. From 2001 to 2014, nine patients underwent salvage total pharyngolaryngectomy with total esophagectomy at the Department of Gastroenterological Surgery, Nagoya University. The mortality and morbidity rates were high at 22% and 89%, respectively. Four patients (44%) developed tracheal necrosis, which in two patients eventually led to lethal hemorrhage. Salvage total pharyngolaryngectomy with total esophagectomy is an uncommon and highly demanding surgical procedure that should be carefully planned and conducted in selected centers of excellence. Measures must be taken to preserve the tracheal blood supply, thus avoiding fatal complications.
Subject(s)
Carcinoma, Squamous Cell/therapy , Esophageal Neoplasms/therapy , Esophagectomy , Head and Neck Neoplasms/therapy , Laryngeal Neoplasms/therapy , Laryngectomy , Neoplasms, Multiple Primary/therapy , Pharyngeal Neoplasms/therapy , Pharyngectomy , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy , Cisplatin/administration & dosage , Esophageal Squamous Cell Carcinoma , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Neoadjuvant Therapy , Retrospective Studies , Salvage Therapy , Squamous Cell Carcinoma of Head and Neck , Treatment OutcomeABSTRACT
We report an experimental demonstration of room-temperature spin transport in n-type Ge epilayers grown on a Si(001) substrate. By utilizing spin pumping under ferromagnetic resonance, which inherently endows a spin battery function for semiconductors connected with a ferromagnet, a pure spin current is generated in the n-Ge at room temperature. The pure spin current is detected by using the inverse spin-Hall effect of either a Pt or Pd electrode on n-Ge. From a theoretical model that includes a geometrical contribution, the spin diffusion length in n-Ge at room temperature is estimated to be 660 nm. Moreover, the spin relaxation time decreases with increasing temperature, in agreement with a recently proposed theory of donor-driven spin relaxation in multivalley semiconductors.
ABSTRACT
To pursue an urgently needed treatment target for esophageal cancer (EC), we investigated the function of the recently discovered melanoma-associated antigen (MAGE)-D4 in squamous cell EC. MAGE-D4 messenger RNA (mRNA) expression was analyzed in nine EC cell lines using quantitative reverse transcription polymerase chain reaction. In 65 surgical specimens of squamous cell EC with no prior neoadjuvant therapy, MAGE-D4â mRNA expression in EC tissues and corresponding normal tissues was analyzed and compared, and evaluated in terms of clinicopathological factors. In representative cases, MAGE-D4 protein distribution was analyzed immunohistochemically. The heterogeneity of MAGE-D4â mRNA expression was confirmed in EC cell lines by quantitative reverse transcription polymerase chain reaction. In surgical specimens, MAGE-D4â mRNA expression was significantly higher in EC tissues than in corresponding normal tissues (P < 0.001). Patients with the highest MAGE-D4â mRNA expression in EC tissues (top quartile, n = 17) had significantly shorter overall survival than patients with low expression (2-year survival: 44% and 73%, respectively, P = 0.006). Univariate analysis identified age (≥65 years), lymphatic involvement, and high MAGE-D4â mRNA expression as significant prognostic factors; high MAGE-D4â mRNA expression was also an independent prognostic factor in multivariable analysis (hazard ratio: 2.194; P = 0.039) and was significantly associated with Brinkman index (P = 0.008) and preoperative carcinoembryonic antigen level (P = 0.002). Immunohistochemical MAGE-D4b expression was consistent with MAGE-D4â mRNA profiling. Our results suggest that MAGE-D4 overexpression influences tumor progression, and MADE-D4 can be a prognostic marker and a potential molecular target in squamous cell EC.
Subject(s)
Antigens, Neoplasm/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/metabolism , Esophageal Neoplasms/metabolism , RNA, Messenger/metabolism , Aged , Aged, 80 and over , Antigens, Neoplasm/genetics , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Disease Progression , Esophageal Neoplasms/genetics , Esophageal Squamous Cell Carcinoma , Female , Humans , Male , Middle Aged , PrognosisABSTRACT
The aim of this study was evaluate the beta blocker atenolol (AT) and ischemic preconditioning (IPC) strategies for tissue protection against systemic effects of intestinal ischemia (I) and reperfusion (R) injury. Forty-two rats were pretreated with AT (1.5 mg · kg(-1)), 0.9% saline solution (SS; 0.1 mL), or IPC and then subjected to prolonged occlusion of the superior mesenteric artery for 60 minutes leading to I followed or not by 120 minutes of R, according to the group. For IPC, 5 minutes of I prior to 10 minutes of R were established. After this process of I or I-R, the right lung of each animal was adequately prepared for staining with hematoxylin and eosin and subsequent histologic analysis for quantification of inflammatory infiltrate was done. The left lung was frozen and prepared for assessment of oxidative stress by the quantification of thiobarbituric acid-reactivity substances (TBARS). Histologic analysis showed an important inflammatory infiltrate in the I-R + SS (I-R + SS = 4.5), which was significantly (P < .05) reduced by IPC (I-R + IPC = 3.0) or AT (I-R + AT = 3.0). Likewise, the TBARS levels were decreased by both strategies (I-R + SS = 0.63; I-R + IPC = 0.23; I-R + AT = 0.38; P < .05). Our results showed that AT and IPC attenuate pulmonary lesions caused by intestinal I and R process.
Subject(s)
Atenolol/pharmacology , Intestines/blood supply , Ischemic Preconditioning/methods , Lung Injury/prevention & control , Lung/blood supply , Reperfusion Injury/prevention & control , Adrenergic beta-1 Receptor Antagonists/pharmacology , Animals , Disease Models, Animal , Lung Injury/etiology , Male , Rats , Rats, Wistar , Reperfusion Injury/complicationsABSTRACT
To study the role of heparin and ischemic preconditioning (IPC) in cardiac injury after intestinal ischemia (I) and reperfusion (R), 54 rats underwent 60 minutes of I, which was produced by occlusion of the superior mesenteric artery, and/or 120 minutes of R. The IPC group had the I procedure stimulation for 5 minutes and R for 10 minutes. The control group was subjected to sham surgery only, and the other groups were injected with saline solution (SS; 0.1 mL) or heparin (100 IU/kg) via the inferior cava vein 5 minutes before I and 5 minutes before R and 55 minutes after the R begins in I-R groups. In all animals, cardiac samples were stained with hematoxylin and eosin for optical microscopy analysis, and other sample was processed for lipid peroxidation determination. In I-R groups, both heparin and IPC showed significant protection compared to the SS group; conversely, in animals subjected only to I, no protection was observed. Moreover, when heparin was associated with IPC, I-R protection was compromised and the ischemic injury increased. Data showed that IPC and heparin attenuated cardiac dysfunction caused by intestinal I and I-R, but when used in association did not show beneficial effects.
Subject(s)
Cardiomyopathies/prevention & control , Heparin/therapeutic use , Intestines/blood supply , Ischemic Preconditioning/methods , Reperfusion Injury/prevention & control , Animals , Anticoagulants/therapeutic use , Cardiomyopathies/etiology , Disease Models, Animal , Male , Rats , Rats, Wistar , Reperfusion Injury/complicationsABSTRACT
The risk of Alzheimer's disease increases following cerebral hypoperfusion. We studied the long-term interaction between low blood flow to the brain and Alzheimer's disease by inducing a transient global ischemic insult in aged 3xTg-AD mice and determining the effects on AD pathology 3-months post injury. We found that global ischemia does not increase the levels of amyloid-ß in these mice. However, the injury did lead to enhanced phosphorylation of the amyloid precursor protein (APP) at the Thr668 site in both the 3xTg-AD mice and wild-type controls. Furthermore, we found an increase in insoluble total tau 3-months post-injury. Together these findings further elucidate the long-term impact of cerebral hypoperfusion on Alzheimer's disease.
Subject(s)
Alzheimer Disease/metabolism , Amyloid beta-Protein Precursor/metabolism , Brain Ischemia/metabolism , Brain/metabolism , tau Proteins/metabolism , Alzheimer Disease/etiology , Amyloid beta-Peptides/metabolism , Animals , Brain Ischemia/etiology , Carotid Artery, Common/pathology , Carotid Stenosis/complications , Mice , Mice, Transgenic , PhosphorylationABSTRACT
Recent studies have demonstrated that lysophospholipids (LPL) play critical roles in several biological signal transduction pathways to maintain the homoeostasis of cells, tissues and organs. Among them, lysophosphatidic acid (LPA) has been identified as a lipid mediator that induces morphological improvement in the epidermis in mice. In this study, we examined the effects of LPL (soybean-derived phospholipids modified with phospholipase A2 and C) compared with LPA. We initially examined the effects of LPA on normal human epidermal keratinocytes (NHEK) focusing on the expression of profilaggrin and serine palmitoyltransferase (SPT) mRNAs. LPA enhanced the expression of profilaggrin and SPT mRNAs via the modulation of Ca(2+) influx. Based on those results, the influence of LPL on NHEK was examined and was expanded to analyse the expression of two tight junction-related proteins, occludin and claudin-1. LPL had similar effects to increase profilaggrin and SPT mRNA expression and also stimulated the expression of occludin and claudin-1 at the mRNA and protein levels. In accordance with these results, LPL elicited significant improvements in surface water content in human skin. These findings indicate that LPL has the potential to strengthen the skin moisturizing capability by up-regulating the expression of mRNAs encoding components important to skin barrier function and skin hydration.
Subject(s)
Calcium/metabolism , Cell Differentiation/drug effects , Keratinocytes/drug effects , Lysophospholipids/pharmacology , Skin/drug effects , Skin/metabolism , Adult , Blotting, Western , Cell Differentiation/physiology , Claudin-1 , Double-Blind Method , Epidermal Cells , Epidermis/drug effects , Epidermis/metabolism , Humans , Keratinocytes/cytology , Keratinocytes/metabolism , Lysophospholipids/administration & dosage , Male , Membrane Proteins/biosynthesis , Membrane Proteins/genetics , Microscopy, Phase-Contrast , Middle Aged , Occludin , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Serine C-Palmitoyltransferase/biosynthesis , Serine C-Palmitoyltransferase/genetics , Skin/cytology , Up-RegulationABSTRACT
In the current review article, evidences on radical surgery for gastric cancer reported in the literature are highlighted. The authors conclude that extended lymphadenectomy offers a statistically significant survival benefit. This benefit is only evident if the operative mortality is less than 2%, as obtained in centers of excellence with a high-volume experience of resection of gastric cancer. Lymphadenectomy should no longer be considered only as a tool for cancer-staging, but also as a beneficial therapeutic measure.
Subject(s)
Digestive System Surgical Procedures , Lymph Node Excision/methods , Stomach Neoplasms/surgery , Chemotherapy, Adjuvant , Humans , Lymphatic Metastasis , Pancreatectomy , Radiotherapy, Adjuvant , Randomized Controlled Trials as Topic , Splenectomy , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/radiotherapyABSTRACT
Klotho mutant mice, defective in the klotho gene, develop multiple age-related disorders with very short lifespans. Introduction of the exogenous klotho gene into these mutant mice leads to an improvement in their phenotypes, while overexpression of this gene in wild-type mice significantly extends their lifespan. These observations suggest that the klotho gene/protein has an anti-aging function. Since there have been only a few reports with some disagreement about results on the CNS of the mutant mice, we tried to clarify whether the CNS neurons generate aging-like features, even in premature stages, using biochemical and morphological approaches. Results obtained from the mutant mice, when compared with wild-type mice, were as follows. Neurofilaments (NFs) were increased significantly in axons, with the subunit proteins showing a significant enhancement in phosphorylation or expression of NF-H or NF-L, respectively. Microtubules in Purkinje cell dendrites were closer to each other, and in the CNS tissue tubulin was unaltered, but microtubule-associated protein (MAP) 2 was significantly reduced in expression. Neuronal cellular organelles were morphologically disordered. Lysosomes, cathepsin D and light chain 3 of MAP1A/B (LC3) were augmented with the appearance of putative autophagy-related structures. Antiapoptotic Bcl-xL and proapoptotic Bax were reduced and enhanced, respectively, and mitogen-activated protein kinase was reduced. Synapse-related proteins and structures were decreased. Neuronal degeneration was evident in hippocampal pyramidal cells, and possibly in Purkinje cells. Astrocytic glial filaments and glial fibrillary acidic protein were increased in density and expression, respectively. Together, the CNS neuronal alterations in klotho mutant mice were quite similar to those found in aged animals, including even premature death, so this mouse should be a more appropriate animal model for CNS aging than those previously reported.
Subject(s)
Aging/physiology , Central Nervous System , Gene Expression Regulation/genetics , Glucuronidase/deficiency , Neurodegenerative Diseases , Neurons/pathology , Animals , Axons/metabolism , Axons/pathology , Axons/ultrastructure , Cathepsin D/metabolism , Central Nervous System/metabolism , Central Nervous System/pathology , Central Nervous System/ultrastructure , Klotho Proteins , Male , Mice , Mice, Knockout , Microscopy, Electron, Transmission/methods , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/pathology , Neurodegenerative Diseases/physiopathology , Neurons/metabolism , Neurons/ultrastructure , bcl-2-Associated X Protein/metabolismABSTRACT
We assessed the biological response to several novel titanium alloys that have promising physical properties for biomedical applications. Four commercial titanium alloys [Super-TIX(R) 800, Super-TIX(R) 51AF, TIMETAL(R) 21SRx, and Ti-6Al-4V (ASTM grade 5)] and three experimental titanium alloys [Ti-13Cr-3Cu, Ti-1.5Si and Ti-1.5Si-5Cu] were tested. Specimens (n = 6; 5.0 x 5.0 x 3.0 mm(3)) were cast in a centrifugal casting machine using a MgO-based investment and polished to 600 grit, removing 250 mum from each surface. Commercially pure titanium (CP Ti: ASTM grade 2) and Teflon (polytetrafluoroethylene) were used as positive controls. The specimens were cleaned and disinfected, and then each cleaned specimen was placed in direct contact with Balb/c 3T3 fibroblasts for 72 h. The cytotoxicity [succinic dehydrogenase (SDH) activity] of the extracts was assessed using the MTT method. Cytotoxicity of the metals tested was not statistically different compared to the CP Ti and Teflon controls (p > 0.05). These novel titanium alloys pose cytotoxic risks no greater than many other commonly used alloys, including commercially pure titanium. The promising short-term biocompatibility of these Ti alloys is probably due to their excellent corrosion resistance under static conditions, even in biological environments.
Subject(s)
Alloys/toxicity , Biocompatible Materials/toxicity , Fibroblasts/drug effects , Titanium/toxicity , Animals , BALB 3T3 Cells , Materials Testing , MiceABSTRACT
To evaluate the effects of endotoxin on the morphology of the equine central, autonomic and enteric nervous system and intestinal muscularis, six Thoroughbred horses with experimentally induced endotoxaemia were examined. The lesions in the central nervous system consisted of perivascular oedema around arterioles, suggesting brain oedema, and ring haemorrhages around veins, similar to those in human patients with septic shock. In the cranial mesenteric ganglia, neuronal cell bodies became pink or red, with shrinkage of cytoplasm indicative of ischaemic changes; intramural and perivascular infiltration by erythrocytes and neutrophils occurred around arterioles in the epineurium (acute focal interstitial inflammation). In addition, transmission electron microscopy revealed oedema of the endoneurium and mesoaxon in the nerve fascicles running inside or outside the ganglia. Myenteric neurons showed shrinkage of the cytoplasm with multiple cytoplasmic vacuoles, suggesting ischaemic changes. Oedematous degeneration and coagulation necrosis of smooth muscle cells, with dissociation of the cells, were prominent in the tunica muscularis. It is suggested that arterionecrosis elicited by endotoxin and frequently observed in the autonomic and enteric nervous system and intestinal muscularis, was the result of vasoconstriction or vasospasm.
Subject(s)
Endotoxemia/chemically induced , Escherichia coli , Horse Diseases/chemically induced , Lipopolysaccharides/toxicity , Nervous System Diseases/chemically induced , Nervous System/drug effects , Animals , Brain/drug effects , Brain/pathology , Disease Models, Animal , Edema/chemically induced , Edema/pathology , Endotoxemia/pathology , Escherichia coli/chemistry , Horse Diseases/pathology , Horses , Intestines/drug effects , Intestines/pathology , Muscle, Smooth/drug effects , Muscle, Smooth/pathology , Myenteric Plexus/drug effects , Myenteric Plexus/ultrastructure , Necrosis/chemically induced , Necrosis/pathology , Nervous System/pathology , Nervous System Diseases/pathology , Peripheral Nerves/drug effects , Peripheral Nerves/ultrastructureABSTRACT
Gastric cancer metastasised to the liver was found to overexpress HER2 at a significantly higher incidence than primary gastric cancers. The purpose of the present study was to investigate the possibility of molecular therapy targeting HER2 overexpression in gastric cancer liver metastasis. We developed three new HER2-overexpressing gastric cancer cell lines (GLM-1, GLM-2, GLM-4) without epidermal growth factor receptor (EGFR) mutations derived from such liver metastasis, two of which had HER2 gene amplifications. All these GLM series of cell lines were highly sensitive to gefitinib in vitro, a specific inhibitor of EGFR tyrosine kinase (Iressa) rather than anti-HER2 antibody trastuzumab (Herceptin), whereas most of the HER2 low-expressing counterparts were not. In these HER2-overexpressing GLM series, protein kinase B (Akt), but not extracellular signal-regulated kinase 1/2 (ERK1/2), was constitutively phosphorylated, and gefitinib efficiently inhibited this Akt phosphorylation, induced strong apoptosis in vitro and exhibited antitumour activity in tumour xenografts in nude mice. This gefitinib-mediated antitumour effect in xenograft was significantly potentiated by trastuzumab treatment. On the other hand, gefitinib-resistant cells (GLM-1R) exhibited increased EGFR expression, followed by constitutive activation of mitogen-activated protein kinase (MAPK) pathway. These results suggest that the antitumour effect of gefitinib is due to the effective inhibition of HER2-driven constitutive activation of phosphatidylinositol-3-kinase (PI3K)/Akt pathway, and that the acquired resistance to gefitinib is due to the constitutive activation of Ras/MAPK pathway in compensation for PI3K/Akt pathway. Gastric cancer liver metastasis with HER2 overexpression would be a potential molecular target for gefitinib and trastuzumab.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Resistance, Neoplasm/physiology , Liver Neoplasms/metabolism , Quinazolines/pharmacology , Receptor, ErbB-2/metabolism , Stomach Neoplasms/metabolism , Animals , Blotting, Western , Cell Line, Tumor , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Gefitinib , Humans , Immunohistochemistry , Liver Neoplasms/pathology , Male , Mice , Mice, Nude , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/metabolism , Stomach Neoplasms/secondaryABSTRACT
Allergenic ingredients extracted from used denture base resin were quantitatively analysed using a gas chromatograph/mass spectrometer and high performance liquid chromatography. Methyl methacrylate (MMA), hydroquinone (HQ), formaldehyde (FMA), benzoyl peroxide (BPO), benzoic acid (BA) and methyl benzoate (MB) were detected in a eluate from all of the dentures, while ethyleneglycol dimethacrylate (DME) was detected in the eluate from 87 dentures in use for <15 years. MMA, HQ, FMA, BPO and MB showed a decrease in correlation to the period of denture use, but continuing to be evident even after 29 years of use. The MMA showed the highest level of elution and a relatively moderate decrease over time. The elution of BA, on the contrary, showed an increase with the period of denture use up to about 10 years and subsequently reached a plateau. Our results indicate that purported allergens exist in the resin base and can be eluted into the oral cavity, even in patients using an old denture for a period of nearly 30 years.