Characteristics of Older People from a Poor Residential Environment in Okinawa, Japan: An Emergency Department-Based Cross-Sectional Study.

BACKGROUND: Evidence for what diseases occur more commonly in older people from a poor residential environment (PRE) is limited. OBJECTIVE: We investigated characteristics, especially the underlying reason (disease) for visiting an emergency department (ED), of older people from a PRE in ED settings. METHODS: A cross-sectional study was conducted on people aged ≥65 years who presented to the EDs of 2 hospitals in Okinawa, Japan, between 2015 and 2019. PRE cases were identified by searching relevant words, such as a house overflowing with garbage from hoarding or housing squalor (gomi-yashiki in Japanese), in electric medical records. Controls (2 controls per case) were randomly selected from those without a PRE, with both living at home and matching each PRE case for age and sex. Characteristics of interest between cases and controls were compared using a χ2 test. RESULTS: PRE cases (n = 67), compared with controls (n = 134), were more often transported by ambulance (79.1% vs. 61.9%; p = 0.01). A family member or relative (43.4%) or professional supporter (20.8%) called an ambulance for most PRE cases. PRE cases were more likely to visit the ED due to injury/fracture (16.4% vs. 8.2%), rhabdomyolysis (11.9% vs. 1.5%), undernutrition/dehydration (10.4% vs. 1.5%), and cancer (9.0% vs. 5.2%) than controls (p < 0.001). PRE cases had a higher prevalence of being underweight (35.4% vs. 14.9%), dementia (41.8% vs. 16.4%), decubitus ulcer (29.9% vs. 8.2%), living alone (73.1% vs. 23.1%), and receiving public welfare assistance (35.8% vs. 9.0%) than controls (all p ≤ 0.001). CONCLUSION: In EDs, older people from a PRE exhibited certain diseases and characteristics.

Computerized data mining analysis of keywords as indicators of the concepts in AHA-BLS guideline updates.

INTRODUCTION: Cardiopulmonary resuscitation (CPR) guidelines have been updated every 5 years since 2000. Significant changes have been made in each update, and every time a guideline is changed, the instructors of each country that ratify the American Heart Association (AHA) must review the contents of the revised guideline to understand the changes made in the concept of CPR. The purpose of this study was to use a computerized data mining method to identify and characterize the changes in the key concepts of the AHA-Basic Life Support (BLS) updates between 2000 and 2015. METHODS: We analyzed the guidelines of the AHA-BLS provider manual of 2000, 2005, 2010, and 2015 using a computerized data mining method and attempted to identify the changes in keywords along with changes in the guideline. RESULTS: In particular, the 2000 guideline has focused on the detailed BLS technique of an individual health care provider, whereas the 2005 and 2010 guidelines have focused on changing the ratio of chest compressions and breathing and changing the BLS sequence, respectively. In the most recent 2015 guideline, the CPR team was the central topic. We observed that as the guidelines were updated over the years, keywords related to CPR and automated external defibrillators (AED) associated with co-occurrence network continued to appear. CONCLUSIONS: Analysis revealed that keywords related to CPR and AED associated with the co-occurrence network continued to appear. We believe that the results of this study will ultimately contribute to optimizing AHA's educational strategies for health care providers.

Inhibition of Crm1-p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation.

Poly(ADP-ribose) polymerase 1 (PARP-1) and p53 are two key proteins in the DNA-damage response. Although PARP-1 is known to poly(ADP-ribosyl)ate p53, the role of this modification remains elusive. Here, we identify the major poly(ADP-ribosyl)ated sites of p53 by PARP-1 and find that PARP-1-mediated poly(ADP-ribosyl)ation blocks the interaction between p53 and the nuclear export receptor Crm1, resulting in nuclear accumulation of p53. These findings molecularly link PARP-1 and p53 in the DNA-damage response, providing the mechanism for how p53 accumulates in the nucleus in response to DNA damage. PARP-1 becomes super-activated by binding to damaged DNA, which in turn poly(ADP-ribosyl)ates p53. The nuclear export machinery is unable to target poly(ADP-ribosyl)ated p53, promoting accumulation of p53 in the nucleus where p53 exerts its transactivational function.

Difference in electromyographic activity between the trapezius muscle and other neck accessory muscles under an increase in inspiratory resistive loading in the supine position.

The activity of the trapezius muscle is reportedly higher than that of other neck accessory muscles under a condition of increased inspiratory pressure in the standing position. The present study aimed to compare the activity of the trapezius muscle with those of the scalene and sternocleidomastoid muscles under a condition of increased inspiratory pressure in the supine position. This study included 40 subjects, and the muscle activity was measured using surface electromyography. Regarding the results, there was a significant difference in the muscle activity between the trapezius muscle and the scalene and sternocleidomastoid muscles (p = 0.003) in both men and women. Post-hoc analysis showed significant differences between trapezius and the other muscles. Moreover, there was no difference between the scalene and sternocleidomastoid muscles (p = 0.596). The increase in the change in electromyography activity of the muscle is greater in the trapezius muscle than in other muscles when the level of inspiratory pressure increases in the supine position.

Noninvasive positive pressure ventilation for treating acute asthmatic attacks in three pregnant women with dyspnea and hypoxemia.

In our case reports, we mentioned about the utility of NPPV therapy in addition to standard pharmacologic therapy for acute asthma exacerbations in pregnant women with dyspnea and hypoxemia compared with that of oxygen therapy alone. Careful patient selection and clinicians' NPPV experience are crucial in optimizing patient outcomes.

Inhibition of IgE-mediated phosphorylation of FcepsilonRIgamma protein by antiallergic drugs in rat basophilic leukemia (RBL-2H3) cells: a novel action of antiallergic drugs.

We examined the effect of antiallergic drugs, azelastine and epinastine, on the expression of FcepsilonRIalpha, beta, and gamma chains and phosphorylation of the gamma chains in rat basophilic leukemia (RBL-2H3) cells. The cells were cultured for 24 h with IgE treatment in the presence of azelastine or epinastine at the concentration of 10(-5) M. The FcepsilonRIalpha mRNA expression was determined by northern blot analysis. The protein level of FcepsilonRI expressed on the plasma membrane was examined following IgE treatment by immunoprecipitation with anti-IgE light chain, followed by western blot analysis with anti-gamma chain of FcR. Azelastine and epinastine had no effect on the FcepsilonRIalpha, beta and gamma mRNA levels. Although the amount of gamma chain assembled into IgE-bound FcepsilonRI was not changed by treatment with azelastine nor epinastine, phosphorylation levels of gamma chains of IgE-bound FcepsilonRI were inhibited by azelastine. The inhibitory effect of azelastine on the IgE-mediated expression of FcepsilonRIgamma protein is not due to their inhibition of mRNA and protein expression, but due to abrogating phosphorylation of the gamma chains, which is important for initiation of FcepsilonRI signaling cascade elicited by IgE interaction.

Elevation of intracellular cAMP up-regulated thrombomodulin mRNA in cultured vascular endothelial cells derived from spontaneous type-II diabetes mellitus model rat.

To investigate whether antihemostatic function of vascular endothelial cells (VECs) is changed in type-II diabetic model rats, the mRNA expressions of tissue-type and urokinase-type plasminogen activator (t-PA and u-PA), thrombomodulin (TM), PA inhibitor type-1 (PAI-1), and phosphodiesterases (type 3A, 3B, and 4D PDEs) were quantitated by the method of comparative reverse transcriptase-polymerase chain reaction (RT-PCR). VECs from type-II diabetic model Otsuka Long-Evans Tokushima Fatty (OLETF) rats and from its normal counterpart (LETO) rats were cultured for 24 h with dibutyryl adenosine 3',5'-cyclic monophosphate (db-cAMP) or a type-3 PDE inhibitor, cilostazol. Intracellular cAMP concentration was determined by the chemiluminescent enzyme-linked immunosorbent assay (ELISA) system. In cultured VECs from OLETF rats, the basal mRNA expressions of u-PA and TM were significantly decreased as compared to those in cultured VECs from LETO rats. TM mRNA expression in cultured VECs from OLETF rats was increased 2.1-fold at 24 h after treatment with db-cAMP (3 mmol/L). Basal mRNA expressions of type 3A, 3B, and 4D PDEs were significantly higher in VECs from OLETF rats than those from LETO rats. After treatment with cilostazol (30 micromol/L), intracellular cAMP was significantly increased at 60 min and TM mRNA expression was increased 1.5-fold at 24 h. Therefore, elevation of intracellular cAMP by db-cAMP or cilostazol up-regulated TM mRNA expression in cultured VECs from OLETF rats.

Antiallergic drugs, azelastine hydrochloride and epinastine hydrochloride, inhibit ongoing IgE secretion of rat IgE-producing hybridoma FE-3 cells.

We asked whether or not antiallergic drugs, azelastine hydrochloride and epinastine hydrochloride, inhibit IgE secretion from IgE-producing hybridoma FE-3 cells. FE-3 cells were cultured in the presence of azelastine or epinastine for 24 h, washed in phosphate-buffered saline , and then recultured in the medium in the absence of the antiallergic drugs. IgE levels in the cultured medium as well as those in the cytoplasm of FE-3 cells were measured by enzyme-linked immunosorbent assay. mRNA levels of Cepsilon, activation-induced cytidine deaminase (AID), XBP-1, and Bip were estimated by northern blot or reverse transcriptase polymerase chain reaction analysis. The activities of nuclear factor-kappa B (NF-kappaB) were analyzed by electrophoretic mobility shift assay (EMSA). Phosphorylation of I kappa B alpha (IkappaBalpha) was analyzed by immunoprecipitation followed by western blot analysis. IgE levels in the cultured medium and in the microsome fraction were lower on the treatment with 10(-5) M azelastine or epinastine than those on the treatment with vehicle. Cepsilon and AID mRNA levels were lower on the treatment with 10(-5) M azelastine than those on the treatment with vehicle, but were not decreased on the treatment with 10(-5) M epinastine. XBP-1 and Bip mRNA levels were not altered following treatment of the antiallergic drugs. Azelastine at 10(-5) M, but not epinastine, reduced DNA binding activity of NF-kappaB and also diminished IkappaBalpha phosphorylation, leading to sustaining IkappaBalpha protein levels. These findings suggest that azelastine exerts its inhibitory effect on the IgE secretion from FE-3 cells through the inhibition of Cepsilon mRNA expression, and that the inhibitory effect of epinastine is, at least in part, due to suppression of IgE synthesis at the post-transcriptional level.

Successful conservative management of a case of caustic esophagitis based on computed tomography assessment.

Case: We describe the case of a female patient who ingested approximately 100 mL of toilet bowl cleaner containing 9.5% hydrochloric acid in a suicide attempt. Upon admission for hematemesis and epigastric pain, she was alert and oriented with stable vital signs. Initial contrast-enhanced computed tomography (CT) demonstrated edematous changes with no evidence of upper gastrointestinal tract perforation. Endoscopy was not performed owing to the high risk of perforation. We managed this patient conservatively. Repeat contrast-enhanced CT revealed mediastinal emphysema on day 2, which resolved by day 6. The patient was subsequently discharged with no apparent strictures of the upper gastrointestinal tract. Outcome: Surgical interventions are frequently required following the ingestion of large amounts of highly concentrated hydrochloric acid; however, this patient was successfully managed conservatively. Conclusion: Contrast-enhanced CT is useful in the assessment of the respiratory and digestive systems and the prediction of potential complications.

Functional relationship among PLK2, PLK4 and ROCK2 to induce centrosome amplification.

The presence of more than 2 centrosomes (centrosome amplification) leads to defective mitosis and chromosome segregation errors, is frequently found in a variety of cancer types, and believed to be the major cause of chromosome instability. One mechanism for generation of amplified centrosomes is over-duplication of centrosomes in a single cell cycle, which is expected to occur when cells are temporarily arrested. There are a growing number of kinases that are critical for induction and promotion of centrosome amplification in the cell cycle-arrested cells, including Rho-associated kinase (ROCK2), Polo-like kinase 2 (PLK2) and PLK4. Here, we tested whether these kinases induce centrosome amplification in a linear pathway or parallel pathways. We first confirmed that ROCK2, PLK2 and PLK4 are all essential for centrosomes to re-duplicate in the cells arrested by exposure to DNA synthesis inhibitor. Using the centrosome amplification rescue assay, we found that PLK2 indirectly activates ROCK2 via phosphorylating nucleophosmin (NPM), and PLK4 functions downstream of ROCK2 to drive centrosome amplification in the arrested cells.

Analysis of centrosome localization of BRCA1 and its activity in suppressing centrosomal aster formation.

BRCA1, a product of a familial breast and ovarian cancer susceptibility gene, localizes to centrosomes and physically interacts with γ-tubulin, a key centrosomal protein for microtubule nucleation and anchoring at centrosomes. Here, we performed a rigorous analysis of centrosome localization of BRCA1, and found that BRCA1 is specifically associated with mother centrioles in unduplicated centrosomes, and daughter centrioles acquire BRCA1 prior to initiation of duplication, and thus duplicated centrosomes are both bound by BRCA1. We further found that BRCA1 suppresses centrosomal aster formation. In addition, we identified a new domain of BRCA1 critical for γ-tubulin binding, which confers not only its localization to centrosomes, but also its activity to suppress centrosomal aster formation.

Regulation of PAI-1 gene expression during adipogenesis.

Obesity is characterized by elevated levels of circulating plasminogen activator inhibitor-1 (PAI-1), which contribute towards the development of secondary disorders such as type 2 diabetes mellitus and cardiovascular complications. This increase in plasma PAI-1 levels is attributed to an increase in PAI-1 derived from adipose tissue. This study shows that adipose tissue evolved into a major PAI-1 producing organ by gaining capacity during adipocyte differentiation to respond to inducers of PAI-1 transcription. This is mediated by a decrease in E2F1 protein levels, an increase in pRB levels and a decrease in pRB phosphorylation, all leading to a decrease in levels of free E2F, a known transcriptional repressor of PAI-1. Depletion of E2F1-3 was sufficient for inducers such as insulin to potently induce PAI-1 gene expression in pre-adipocytes. Conversely, forced release of pRB-bound endogenous E2F using cell-penetrating peptides can suppress PAI-1 gene expression in adipocytes. This study describes the novel paradigm of cellular differentiation-associated increase in PAI-1 gene expression which is mediated by a decrease in repressor activity, and describes a way of desensitising terminally differentiated cells to PAI-1 inducing agents by restoring endogenous repressor activity.

RNA interference targeting embryonic myosin heavy chain isoform inhibited mRNA expressions of phenotype markers in rabbit cultured vascular smooth muscle cells.

To investigate whether the knockdown of SMemb gene expression induces phenotypic modulation of vascular smooth muscle (VSM) cells toward a contractile type, we constructed a siRNA targeting the 3' untranslated region (UTR) of SMemb gene (SMemb-siRNA). The SMemb-siRNA was introduced into cultured rabbit VSM cells for 48 h at 37 degrees C by the lipofection method. The mRNA expressions were estimated by comparative reverse transcription-polymerase chain reaction (RT-PCR). SMemb-siRNA significantly decreased the ratio of SMemb to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression in a dose-dependent manner (P < 0.01): 0 nM, 0.90 +/- 0.08; 100 nM, 0.43 +/- 0.07. Immunofluorescence and immunoblot analyses demonstrated that SMemb-siRNA markedly decreased SMemb protein expression to 56% +/- 7.8% (P < 0.01). Other MHC isoform (SM1 and SM2) mRNA expressions were not changed. The relative mRNA expressions of other phenotype markers (plasminogen activator inhibitor (PAI)-1 and beta-actin) were significantly decreased by SMemb-siRNA to 71% +/- 7.5% and 61% +/- 7.5%, respectively (P < 0.01). Expression of smooth muscle (SM) alpha-actin protein and cell proliferation was not changed by SMemb-siRNA. Thus, SMemb gene might be involved in the transcription of PAI-1 and beta-actin, but not involved in SM alpha-actin and cell proliferation in cultured VSM.

Involvement of Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP)-1 in the potentiation of C epsilon mRNA expression in human tonsil-derived cells.

The aim of our study was to investigate a possible correlation between Epstein-Barr virus (EBV) infection status, including its latent gene expression, and expression of allergy-related genes in human tonsil-derived cells. In the tonsil-derived cells from the patients undergoing routine tonsillectomies for palatine tonsil hypertrophy or tonsillar focal infection, the presence of EBV DNA and mRNA expressions of latent membrane protein (LMP)-1, C epsilon chain, and activation-induced cytidine deaminase (AID) were detected by PCR and RT-PCR analysis, respectively. Of all the 12 patients, PCR products amplified from EBV DNA BamHI W fragment were detected in the tonsils from the 10 patients (83.3%). LMP1 mRNA expressions were confirmed in the six patients (50%). Both LMP1 mRNA expressions and EBV DNA were detected in the five patients. EBV DNA, but not LMP1 mRNA expression, was detected in the five patients. LMP1 mRNA expression, but not EBV DNA, was detected in one patient. In one patient, neither EBV DNA nor LMP1 mRNA expression was confirmed. C epsilon mRNA expressions were confirmed in all the 12 patients along with AID mRNA expressions. The degree of C epsilon mRNA expression, however, varied with the patients. The Fisher's exact probability test revealed a statistically significant correlation between LMP1 and C epsilon gene expressions, indicating that C epsilon mRNA expression level was significantly higher in the LMP1 positive samples than in the negative samples. On the other hand, there was no significant correlation between AID and LMP1 mRNA expressions. Thus, EBV infection is a notable factor capable of exacerbating allergic inflammation.

Modification of Cepsilon mRNA expression by EBV-encoded latent membrane protein 1.

To evaluate the effect of expression of latent membrane protein (LMP) 1 encoded by Epstein-Barr virus (EBV) on Cepsilon mRNA expression, mRNA levels were examined by RT-PCR or Northern blot analysis upon transient transfection of LMP1 in the splenocytes derived from Brown-Norway rats with or without immunization with 2,4-dinitrophenyl-conjugated Ascaris suum antigen. Splenocytes were transfected with LMP1 expression vector, pSG5-LMP1, using lipofection method. Cepsilon mRNA levels were considerably increased by transfection with pSG5-LMP1 in the splenocytes derived from the nonimmunized rats; however, Cepsilon mRNA levels were decreased in the splenocytes derived from the immunized rats. Cepsilon mRNA expression in IgE-producing cells are modulated by LMP1, which might depend on the differentiation status of B cells upon exposure to allergen.

Identification and modulation of a caveolae-dependent signal pathway that regulates plasminogen activator inhibitor-1 in insulin-resistant adipocytes.

Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathogenesis of obesity-driven type 2 diabetes mellitus and associated cardiovascular complications. Here, we show that perturbation of caveolar microdomains leads to insulin resistance and concomitant up-regulation of PAI-1 in 3T3L1 adipocytes. We present several lines of evidence showing that the phosphatidylinositol 3-kinase (PI3K) pathway negatively regulates PAI-1 gene expression. Insulin-induced PAI-1 gene expression is up-regulated by a specific inhibitor of PI3K. In addition, serum PAI-1 level is elevated in protein kinase Balpha-deficient mice, whereas it is reduced in p70 ribosomal S6 kinase 1-deficient mice. The PI3K pathway phosphorylates retinoblastoma protein (pRB), known to release free E2 (adenoviral protein) factor (E2F), which we have previously demonstrated to be a transcriptional repressor of PAI-1 gene expression. Accordingly, cell-penetrating peptides that disrupt pRB-E2F interaction, and thereby release free E2F, are able to suppress PAI-1 levels that are elevated during insulin-resistant conditions. This study identifies a caveolar-dependent signal pathway that up-regulates PAI-1 in insulin-resistant adipocytes and proposes a previously undescribed pharmacological paradigm of disrupting pRB-E2F interaction to suppress PAI-1 levels.

Azelastine and suplatast shorten the distribution half-life of IgE in rats.

We aim to clarify whether suplatast and azelastine (anti-allergic drugs) can shorten the half-life of imnunoglobulin E (IgE) in the circulating blood. Thirty Wistar rats were divided into six groups. Distilled water or anti-allergic drugs were given orally for 6 days after the first sensitization. Two milligrams of monoclonal dinitrophenyl (DNP)-specific rat IgE was administered to the rats, which had been given suplatast or azelastine orally. The level of DNP-specific rat IgE in the serum was estimated by IgE-capture enzyme-linked immunosorbent assay, and the turnover of IgE was analyzed from its pharmacokinetic parameters. The elimination half-life of rat IgE was about 12 h irrespective of the sensitized state. The intercompartmental rate constants (Kct and Ktc) in the suplatast-administered or azelastine-administered group were larger than those of the distilled water-administered group under non-sensitized conditions. These findings suggested that the anti-allergic drugs used in the present study facilitated the excretion of IgE from the circulation in rats.

Mast cell-derived VEGF enhances the passage of IgE FE-3 through the rat aortic endothelial cell monolayer.

BACKGROUND: It is well known that the IgE-mediated allergic reaction in various extravascular tissues is induced by the mutual interaction of IgE, target cells (mast cells, MCs) and allergens. However, so far little has been known about the detailed mechanism whereby IgE in the circulating blood is transferred to the extravascular tissue. To examine whether or not MCs are involved in the permeability of IgE across rat aortic endothelial cells (RAECs) in vitro, we determined the permeability constant (PC) of dinitrophenyl-specific rat IgE (IgE FE-3) using a dual chamber system. METHODS: Isolated RAECs obtained by a primary explant technique were seeded on a collagen-coated membrane in the upper chamber. MCs were collected from the peritoneal cavity of Wistar rats and suspended in the lower chamber. The time-dependent changes in concentration of IgE FE-3 (IgE) in the upper and lower chambers were measured by IgE capture ELISA after addition of IgE (10 microg/ml) to the upper chamber. RESULTS: The cultured medium of IgE-stimulated MCs significantly increased the PC of IgE (9.86 +/- 0.46 x 10(-6) cm/s), as compared to the value to which calcium ionophore A 23187-stimulated MCs increased the PC of IgE (7.97 +/- 0.21 x 10(-6) cm/s). The increase of PC by IgE-stimulated MCs was most strongly inhibited by suramin (92.3% +/- 1.89), and was weakly inhibited by tranexamic acid, cimetidine and diphenhydramine. In addition, the PC of IgE was increased with the increase in the MC-derived vascular endothelial growth factor/permeability factor (VEGF). CONCLUSIONS: After IgE is transferred from the circulating blood to the extravascular tissue, it may bind to Fc epsilon RI of the MC and the other Fc epsilon RI-bearing cells. The MC is then activated through the interaction of IgE and Fc epsilon RI. Release of VEGF from the activated MC increases, and the VEGF enhances the permeability of IgE.