Association of Japanese cedar pollinosis and sensitization with HLA-DPB1 in the Japanese adolescent

Background

Allergic rhinitis (AR) is a heterogeneous disorder that significantly affects daily activity, work productivity, sleep, learning, and quality of life in all generations. Japanese cedar (JC) pollen is the most common allergen responsible for the development of AR in Japan. AR caused by JC pollen is considered to be a multifactorial inheritance disease that is caused by both environmental and genetic factors. The aim of this study was to investigate whether Human Leukocyte Antigen-DPB1 (HLA-DPB1) is associated with JC sensitization/pollinosis.

Usefulness of prone-position computed tomography as preoperative simulation prior to thoracoscopic esophagectomy for thoracic esophageal cancer

Purpose

The study aimed to evaluate the usefulness of prone-position computed tomography (CT) for predicting relevant thoracic procedure outcomes in minimally invasive esophagectomy (MIE) for thoracic esophageal cancer.

Materials and methods

A total of 59 patients underwent esophagectomy between May 2019 and December 2020 in Tokai University Hospital. Preoperative CT imaging was conducted with the patient in both the supine and prone positions, and the magnitude of change in the intramediastinal space was calculated. In the 56 patients (94.9%) who had undergone MIE, the effects of such a difference on the surgical outcomes were analyzed.

Results

A significant correlation of the magnitude of change in VE (distance between ventral aspect of the vertebral body and the midpoint of the esophagus) with the surgical outcome was revealed in the 17 patients (30.4%) in whom the magnitude of change in VE was over the 75th percentile. That is, in this subgroup, the magnitude of change in VE showed a negative correlation with the thoracic operation time (rs?=???0.57, p?=?0.01) and blood loss during the thoracic procedure (rs?=???0.46, p?=?0.01). Multivariate analysis identified a magnitude of change in VE?≥?9 mm (OR?=?0.14, p?=?0.03) as an independent risk factor for postoperative pneumonia.

Conclusions

This study indicates that preoperative prone-position CT imaging is useful for predicting the level of ease or difficulty of securing an adequate operative field, surgical outcomes, and the risk of postoperative pneumonia in MIE.

     

A novel murine model of pharyngeal candidiasis with local symptoms characteristic of pharyngeal thrush produced by using an inhaled corticosteroid.

We established a novel murine model of pharyngeal candidiasis maintaining stable yeast population and local symptoms characteristic of pharyngeal thrush. The persistent Candida-infection was prolonged by inhalation of beclomethasone dipropionate corticosteroid. The severity of infection lesions was evaluated by determining viable cell number of Candia albicans and scores representing symptomatic curd-like white patch on pharyngeal tissue. The utility of this model was shown by the disappearance of lesions and fungal cells after treatment with fluconazole (FLCZ). The model would be useful for evaluating new chemotherapeutic or immunotherapeutic approaches against pharyngeal candidiasis, as well as in pathological studies.     

Distinct mechanism of cell death is responsible for tunicamycin-induced ER stress in SK-N-SH and SH-SY5Y cells

In order to elucidate underlying mechanism of cell death pathways in neuronal cells in humans, we studied responsible pathways involved in the endoplasmic reticulum (ER) stress-induced cell death in neuroblastoma cells, SK-N-SH and its neuroblast-type subclone SH-SY5Y cells. A time-dependent induction of ER chaperons, glucose regulated protein (GRP)78 and GRP94, was observed after treatment with tunicamycin (TM), and cell death was also induced concomitantly in both cells. Although the pro-caspase-12-like protein was defined in both cells, a decrease in the protein was observed in only SH-SY5Y cells after exposure to TM. In contrast, pro-caspase-4 was detected in only SK-N-SH cells, and the cleaved-form was induced by the treatment with TM. A caspase-4 inhibitor, Z-LEVD-FMK attenuated TM-induced cell death in SK-N-SH cells. Calpain- and caspase-3-mediated proteolysis of alpha II-spectrin was also increased after the treatment with TM in both cells. A calpain inhibitor, calpeptin, repressed TM-induced cell death in only SK-N-SH cells. GADD153/C/EBP homologous protein (CHOP) was significantly induced after exposure to TM in only SH-SY5Y cells and RNA interference to GADD153/CHOP repressed TM-induced cell death. These results demonstrate that induction of GADD153/CHOP plays a pivotal role in mechanism of ER stress-induced cell death in SH-SY5Y cells, on the other hand, cleavage of pro-caspase-4 by activation of calpain play a crucial role in SK-N-SH cells. It is also suggested that the relevance of caspase-4 to ER stress is cell-specific even between human-origin cell lines.     

Neural activities in the substantia nigra modulated by stimulation of the orofacial motor cortex and rhythmical jaw movements in the rat

Neurons related to jaw movements in the substantia nigra pars reticulata were explored by examining changes in their neural activities in response to electrical stimulation of the orofacial sensorimotor cortex and during rhythmical jaw movements induced by mechanical stimulation applied to the oral cavity in the rat. Out of 80 neurons tested, 59 showed changes in their firing patterns of activities in response to the electrical stimulation of the cortex. The responding neurons were mainly located in the dorsolateral part of the substantia nigra pars reticulata. The substantia nigra pars reticulata neurons showing responses were classified into the following five types according to their response patterns: (1) an inhibition preceded by an early excitation and followed by a late excitation (n = 26), (2) an inhibition preceded by an early excitation but not followed by a late excitation (n = 7), (3) an inhibition not preceded by an early excitation but followed by a late excitation (n = 2), (4) an inhibition without early or late excitations (n = 7) and (5) an excitation without an inhibition (n = 17). Out of 18 neurons responding to the cortical stimulation, 11 (61.1%) increased or decreased their neural activities during rhythmical jaw movements. Some of these neurons had a projection to the lateral part of the superior colliculus (n = 5) and/or to the parvicellular reticular formation (n = 2). These results provide first neurophysiological evidence for neurons in the dorsolateral part of the substantia nigra pars reticulata with inputs from and outputs to the areas related to jaw movements. These neurons may participate in the control of jaw movements in the rat.     

Protective effect of S-allyl-L-cysteine,a garlic compound,on amyloid beta-protein-induced cell death in nerve growth factor-differentiated PC12 cells

Aged garlic extract (AGE) contains several neuroactive compounds, including S-allyl-L-cysteine (SAC) and allixin. We characterized cell death induced by amyloid beta-protein (Abeta), 4-hydroxynonenal (HNE), tunicamycin, an endoplasmic reticulum (ER) stressor, or trophic factor deprivation, and investigated whether and how SAC could prevent this in nerve growth factor (NGF)-differentiated PC12 cells, a model of neuronal cells. Exposure of the cells to amyloid beta-protein(1-40) (Abeta(1-40)) decreased the extent of [3-(4,5)-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT) reduction activity and loss of neuronal integrity, but these effects were not prevented by Ac-DEVD-CHO, a caspase-3 inhibitor. Simultaneously applied SAC protected the cells against Abeta-induced cell death in a concentration-dependent manner. It also protected them against tunicamycin-induced neuronal death. In contrast, it afforded no protection against cell death induced by HNE and trophic factor deprivation, which is mediated by a caspase-3-dependent pathway. These results suggest that SAC may selectively protect cell death induced by Abeta and tunicamycin, which may be triggered by ER dysfunction in NGF-differentiated PC12 cells.     

Graphic and movie illustrations of human prenatal development and their application to embryological education based on the human embryo specimens in the Kyoto collection.

Morphogenesis in the developing embryo takes place in three dimensions, and in addition, the dimension of time is another important factor in development. Therefore, the presentation of sequential morphological changes occurring in the embryo (4D visualization) is essential for understanding the complex morphogenetic events and the underlying mechanisms. Until recently, 3D visualization of embryonic structures was possible only by reconstruction from serial histological sections, which was tedious and time-consuming. During the past two decades, 3D imaging techniques have made significant advances thanks to the progress in imaging and computer technologies, computer graphics, and other related techniques. Such novel tools have enabled precise visualization of the 3D topology of embryonic structures and to demonstrate spatiotemporal 4D sequences of organogenesis. Here, we describe a project in which staged human embryos are imaged by the magnetic resonance (MR) microscope, and 3D images of embryos and their organs at each developmental stage were reconstructed based on the MR data, with the aid of computer graphics techniques. On the basis of the 3D models of staged human embryos, we constructed a data set of 3D images of human embryos and made movies to illustrate the sequential process of human morphogenesis. Furthermore, a computer-based self-learning program of human embryology is being developed for educational purposes, using the photographs, histological sections, MR images, and 3D models of staged human embryos.     

Expression of thioredoxin and thioredoxin-binding protein-2 in the liver of patients with chronic hepatitis C as a predictor of response to interferon therapy

Oxidative stress contributes to the pathogenesis of various hepatic injuries. Thioredoxin (TRX) is an indicator of oxidative stress, reported to be increased in the serum of patients with chronic hepatitis C with the progression of fibrosis. The aim of this study was to evaluate the clinical significance of the expression of TRX and thioredoxin-binding protein-2 (TBP-2), which is a negative regulator of TRX function, in the liver of patients with chronic hepatitis C and the relationship of this to the efficacy of interferon (IFN) treatment. A retrospective study was performed using the liver biopsy specimens obtained before IFN treatment from 69 patients with chronic serotype 1 hepatitis C virus (HCV) infection. TRX and TBP-2 mRNA levels in the liver biopsy specimens were amplified by real-time RT-PCR. The serum TRX protein level was estimated with a sandwich enzyme-linked immunosorbent assay kit, and the expression of TRX protein in the liver was examined immunohistochemically in 19 patients. There was no association between the serum TRX level and the TRX level in the liver. There was a significant correlation between the expression level of TRX protein in the liver and the TRX mRNA level in the liver. TRX and TBP-2 levels in the liver tended to decrease slightly with increased fibrosis stage, although not significantly. The TRX level in the liver tended to increase with hepatitis activity index, although not significantly. TBP-2 mRNA levels in the liver were significantly higher in responders than non-responders to the IFN therapy (p<0.05). Among patients who had a high viral load of >850 KIU/ml, the TRX level in the livers of non-responders was significantly lower than that in the livers of responders (p<0.05). TRX and TBP-2 mRNA levels in the liver before IFN therapy may predict the outcome of IFN therapy in patients with chronic serotype 1 HCV infection.     

Enhanced neurogenesis in the ischemic striatum following EGF-induced expansion of transit-amplifying cells in the subventricular zone

In the subventricular zone (SVZ) of the adult mammalian brain, neural stem cells continually produce transit-amplifying precursors, which generate neuroblasts migrating into the olfactory bulb. Previous studies have suggested that SVZ cells also have the capacity to generate some striatal neurons after cerebral ischemia. The infusion of epidermal growth factor (EGF) has been demonstrated to increase the number of these regenerated neurons. However, which cell types in the SVZ are stimulated to proliferate or differentiate after EGF infusion remains unknown. In this paper, we demonstrated that cerebral ischemia results in an increase in the number of EGF receptor (EGFR)-positive transit-amplifying cells in the SVZ. EGF infusion into the ischemic brain caused the number of transit-amplifying cells to increase and the number of neuroblasts to decrease. On the other hand, after an interval of 6 days after the discontinuation of EGF infusion, a significant increase in the number of neuroblasts was found, both in the striatum and the SVZ. These results suggest that the replacement of neurons in injured striatum can be enhanced by an EGF-induced expansion of transit-amplifying cells in the SVZ.     

Characterization of Pseudomonas aeruginosa isolates from patients with urinary tract infections during antibiotic therapy

We characterized susceptibilities and genotypes in a series of Pseudomonas aeruginosa isolates from five cases of urinary tract infections (UTIs) to evaluate clonal shifts of carbapenem resistance. In one case, a series of isolates showed different susceptibility patterns for carbapenems but an identical genotype. In another case, genotypes varied among 4 P. aeruginosa isolates from recurrent UTIs over 9 months. Although the patient had been treated with no antibiotic immediately before isolation, the susceptibility patterns for carbapenems and ceftazidime varied. Further analysis in these two cases of outer membrane protein profiles showed that loss of OprD production resulted in reduced susceptibilities to carbapenems in all of the carbapenem-resistant isolates. Loss of OprD production was likely due to oprD gene inactivation in both of cases, since the carbapenem-resistant isolates showed no cross resistance to levofloxacin and chloramphenicol compared with the carbapenem-susceptible isolates. There was another case in which all isolates showed similar susceptibility patterns for carbapenems and ceftazidime, and an identical genotype during the intermittent use of antibiotics over 5 months. In two cases, a single course of antibiotic therapy resulted in eradication of P. aeruginosa. Our results suggest that clonal shifts of carbapenem resistance in P. aeruginosa may result from loss of OprD during antibiotic treatment. Therefore, it is important for clinicians to monitor susceptibilities to antibiotics, especially carbapenems, in P. aeruginosa isolated during therapy.