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HNF4α is a culprit gene product for a monogenic and dominantly-inherited form of diabetes, referred to as MODY1 (Maturity Onset Diabetes of the Young type 1). Reduced HNF4α activities have been linked to impaired insulin secretion and β-cell function. Numerous mutations have been identified from the patients and they have been instructive as to the individual residue's role in protein structure-function and dysfunction. As a member of the nuclear receptor (NR) superfamily, HNF4α is made of characteristic modular domains and it functions exclusively as a homodimer despite its sequence homology to RXR, a common heterodimer partner of non-steroidal NRs. Transcription factors commonly dimerize to enhance their molecular functions mainly by facilitating the recognition of double helix target DNAs that display an intrinsic pseudo-2-fold symmetry and the recruitment of the remainder of the main transcriptional machinery. HNF4α is no exception and its dimerization is maintained by the ligand binding domain (LBD) mainly through the leucine-zipper-like interactions at the stalk of two interacting helices. Although many MODY1 mutations have been previously characterized, including DNA binding disruptors, ligand binding disruptors, coactivator binding disruptors, and protein stability disruptors, protein dimerization disruptors have not been formally reported. In this report, we present a set of data for the two MODY1 mutations found right at the dimerization interface (L332 P and L328del mutations) which clearly exhibit the disruptive effects of directly affecting dimerization, protein stability, and transcriptional activities. These data reinforced the fact that MODY mutations are loss-of-function mutations and HNF4α dimerization is essential for its optimal function and normal physiology., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Ischemia and reperfusion (I/R) of the lungs induces massive superoxide radical production. On the other hand, matrix metalloproteases (MMPs) were shown to play an essential role in I/R-associated lung injury. We aimed to investigate the lung-protective efficacy of intravenous superoxide dismutase (SOD) administration and its relation with MMPs activity in the lungs subsequent to I/R injury., Methods: Twenty-two male Sprague-Dawley rats were divided into a sham group (n = 6), a unilateral lung I/R group (n = 8), and a SOD-treated lung I/R group (n = 8). Unilateral lung ischemia was conducted by occluding the left lung hilum for 90 min, followed by 5 hours of reperfusion through release of the occlusion. In the SOD-treated group, SOD was administered intravenously during the first hour of reperfusion. We assessed the protein contents in the broncho-alveolar lavage fluid (PCBAL) as a marker for protein permeability and lung wet-to-dry weight ratio (W/D) for lung water content. We also measured levels of lipid peroxidation and MMP activity in the lungs, by tissue malonedealdehyde (MDA) level with the use of enzyme-linked immunoassay, and the gelatin zymography technique, respectively., Results: Forty-eight hours of left-lung I/R significantly increased PCBAL (P < .001), W/D (P < .05), tissue MDA level (P < .05), and MMP-9 and MMP-2 activity. SOD treatment attenuated I/R-induced contralateral lung injury, reducing pulmonary permeability, lipid peroxidation, and MMP activities., Conclusions: I/R injury of the left lung induced increases in W/D, PCBAL, MDA level, and MMP-9 activity in the right lung. SOD treatment during the first hour of a 5-hour reperfusion protected the lung through suppressing MMP-9 activity and reducing tissue lipid peroxidation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Nanotitanium dioxide particle (nTiO2) inhalation has been reported to induce lung parenchymal injury. After inhalation of nTiO2, we monitored changes in 5-lipoxygenase, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) mRNA in rat lung tissue. Lung function parameters include specific airway resistance (SRaw), peak expiratory flow rate (PEF), functional residual capacity (FRC), and lung compliance (Cchord); blood white blood cell count (WBC), nitric oxide (NO), hydrogen peroxide, and lactic dehydrogenase (LDH); and lung lavage leukotriene C4, interleukin 6 (IL6), tumor necrotic factor α (TNFα), hydroxyl radicals, and NO. Leukotriene receptor antagonist MK571 and 5-lipoxygenase inhibitor MK886 were used for pharmacologic intervention. Compared to control, nTiO2 exposure induced near 5-fold increase in 5-lipoxygenase mRNA expression in lung tissue. iNOS mRNA increased while eNOS mRNA decreased. Lavage leukotriene C4; IL6; TNFα; NO; hydroxyl radicals; and blood WBC, NO, hydrogen peroxide, and LDH levels rose. Obstructive ventilatory insufficiency was observed. MK571 and MK886 both attenuated the systemic inflammation and lung function changes. We conclude that inhaled nTiO2 induces systemic inflammation, cytokine release, and oxidative and nitrosative stress in the lung. The lipoxygenase pathway products, mediated by oxygen radicals and WBC, play a critical role in the obstructive ventilatory insufficiency induced by nTiO2.

A straightforward electrochemical deposition process was developed to grow gold nanostructures, including nanocoral, nanothorn, branched belt, and nanoparticle, on carbon electrodes by reducing HAuCl4 under constant potentials in mixtures containing CTAC and/or NaNO3. Among the nanostructures, the quasi-one-dimensional nanocoral electrode showed the highest surface area. Because of this, it provided excellent electrochemical performances in cyclic voltammetric (CV) studies for kinetic-controlled enzyme-free glucose oxidation reactions. In amperometric studies carried out at 0.200 V in PBS (pH 7.40, 0.100 M), the nanocoral electrode showed the highest anodic current response. It also offered the greatest sensitivity, 22.6 μAmM(-1)cm(-2), an extended linear range, 5.00×10(-2) mM to 3.00×10(1) mM, and a low detection limit, 1.00×10(1) μm among the electrodes investigated in this study. In addition, the glucose oxidation by the nanocoral electrode started at -0.280 V, more negative than the one of using a commercial Au electrode as the working electrode. This is attributed to the presence of exposed Au (110) surfaces on the electrode. The feature was applied to oxidize glucose selectively in the presence of ascorbic acid (AA) and uric acid (UA), common interferences found in physiological analytes. With an applied voltage at -0.100 V, the AA oxidation (started at -0.080 V) can be avoided while the glucose oxidation still provides a significant response.

Study Objective: To establish a predictive scoring system and to determine its effectiveness for severe acute respiratory syndrome (SARS) cases confirmed by RT-PCR in patients with fever., Methods: A study was conducted of 484 consecutive patients seen in the emergency department (ED) of our tertiary care center during the SARS outbreak in Taiwan. The scoring system was divided into triage and screening station stages. Data were analysed with multivariable and logistic regression analysis., Results: Of 737 patients who presented to our ED for possible SARS from March to June 2003, we enrolled 484 patients with a temperature >38.0 degrees C (>100.3 degrees F) (age >18 years). Dyspnoea, diarrhoea, travel, close contact, hospital exposure, and household history were identified as predictive indicators in the triage stage. The triage score was the total of six items. With a one-point cutoff value, the sensitivity and specificity were 81.8% (18/22) and 73.6% (340/462). Leukocytosis, thrombocytopenia, lymphopenia, and CXR were identified as predictive indicators in the fever screening stage. Screening station scores (the sum of 10 items) consisted of triage scores, white blood cell count, and CXR. With a three-point cutoff value, the sensitivity and specificity were 95.5% (21/22) and 87.2% (403/462)., Conclusions: Syndromic and traditional surveillance play a role in early identification of SARS in an endemic area. The SARS scoring system described is easily applicable and highly effective in screening patients during outbreaks.

Upper gastrointestinal (GI) hemorrhage is a common presentation to an emergency department. Often, the diagnosis is peptic ulcer disease in which vague or sharp abdominal pain is associated with bleeding. In contrast, intussusception is a rare cause of abdominal pain and coincident GI bleeding. In this case, we report a 41-year-old woman who had an intussuscepting jejunal obstruction due to a hamartoma of the small bowel. The diagnosis was established by ultrasonography. In review of the literature, abdominal pain and bleeding are two common manifestations of intussusception when the lesion originates in the small bowel. Intussusception is frequently included in the differential diagnosis of pediatric patients with coincident abdominal pain and bleeding. However, it is rarely mentioned as an adult cause of these two findings. Because of the delayed and nonspecific presentations of abdominal discomfort in adult patients with intussusception, the diagnosis is often delayed. This case points out the need for considering intussusception even in middle-aged patients whose initial presentation is concomitant bleeding and pain.