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1.
Cureus ; 16(4): e58032, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38738104

ABSTRACT

Electronic health record (EHR) systems have developed over time in parallel with general advancements in mainstream technology. As artificially intelligent (AI) systems rapidly impact multiple societal sectors, it has become apparent that medicine is not immune from the influences of this powerful technology. Particularly appealing is how AI may aid in improving healthcare efficiency with note-writing automation. This literature review explores the current state of EHR technologies in healthcare, specifically focusing on possibilities for addressing EHR challenges through the automation of dictation and note-writing processes with AI integration. This review offers a broad understanding of existing capabilities and potential advancements, emphasizing innovations such as voice-to-text dictation, wearable devices, and AI-assisted procedure note dictation. The primary objective is to provide researchers with valuable insights, enabling them to generate new technologies and advancements within the healthcare landscape. By exploring the benefits, challenges, and future of AI integration, this review encourages the development of innovative solutions, with the goal of enhancing patient care and healthcare delivery efficiency.

2.
Cureus ; 16(3): e56940, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38665746

ABSTRACT

Epiglottitis is an uncommon condition in adults, and recurrent episodes are rare. We report a 58-year-old male who had a second episode of epiglottitis nine years after his first. Our patient's immunologic profile obtained during his hospitalization revealed a significantly low absolute cluster of differentiation 4+ (CD4+) T lymphocyte count of 77 cells/mcL and a low immunoglobulin G (IgG) level of 635 mg/dL. Our patient was successfully managed with broad-spectrum antibiotics and corticosteroids. Given the known ability of short-term corticosteroids and acute inflammation's effect on lymphocyte populations, the significance of these laboratory values remains unclear due to our patient's unwillingness to undergo further diagnostic testing following discharge from our facility. We have considered multiple underlying etiologies for our patient's predisposition to developing this rare, recurrent, infectious manifestation; however, the exact cause is yet to be fully elucidated.

3.
Cureus ; 16(2): e53514, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38440019

ABSTRACT

Renal tubular acidosis (RTA) involves dysfunction of the renal tubular system, which leads to electrolyte abnormalities and acid-base dysregulation. The case we present here discusses a patient with a past medical history of psoriatic arthritis who presented to the emergency department with progressive generalized weakness and anorexia in the preceding four weeks. She was found to have profound hypokalemia (1.2 mmol/L), hyperchloremic metabolic acidosis, and multiple other electrolyte abnormalities. Following an extensive workup, her principle problem was deemed to be distal (type 1) RTA. She was treated with sodium bicarbonate, spironolactone, and aggressive rehydration, which eventually led to the stabilization of her electrolytes alongside clinical improvement over the course of an eight-day hospitalization. The workup did not reveal a clear etiology for the RTA. One month prior to hospitalization, she was started on apremilast, a new medication for her psoriatic arthritis. Given the limited availability of alternative explanations and the temporality of clinical manifestations, our findings raise suspicion that apremilast might be associated with her clinical presentation.

4.
Immunol Invest ; 48(8): 822-834, 2019 Nov.
Article in English | MEDLINE | ID: mdl-30917710

ABSTRACT

Th17 cells of the intestine and colon can produce several important cytokines during mucosal inflammation. However, few studies have focused on the role of IL-26 in intestinal inflammations. Colonic epithelial cells express receptors for IL-26, and this cytokine has been shown to induce the HT-29 colonic epithelial cell line to produce the chemokine CXCL8. However, epithelial cells would function in a cytokine network environment during mucosal inflammation and any effect of IL-26 on colonic epithelial cell chemokine responses could be affected by the presence of other potent pro-inflammatory cytokines like TNF-α and IL-1. Therefore, we investigated the effect of IL-26 with TNF-α or IL-1 on colonic epithelial cell line secretion of CXCL8. IL-26 alone had no effect on HT-29 or DLD1 cell line CXCL8 secretion. Yet, IL-26 was found to significantly enhance TNF-α-induced, but not IL-1-induced, CXCL8 secretion, but only at high levels of TNF-α. Similar results were seen with DLD1 cells. IL-26 did not enhance TNF-α-induced CXCL8 mRNA levels and did not affect TNF-α-induced IκBα phosphorylation or degradation. However, signaling through ERK and p38 MAPK were determined to be involved in the enhancing effect of IL-26 on the TNF-α-induced CXCL8 secretion, perhaps through known post-translational effects. These results suggest that the role of IL-26 in intestinal inflammation may be limited to enhancing CXCL8 secretion in the presence high levels of TNF-α, such as may occur in inflammatory bowel disease. Abbreviations: DMEM, Dulbecco's Modified Eagle's Medium; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IBD, inflammatory bowel disease; IL, interleukin; ITS, insulin, transferrin, selenium; TBS, Tris buffered saline; TNF, tumor necrosis factor.


Subject(s)
Epithelial Cells/drug effects , Interleukin-8/metabolism , Interleukins/pharmacology , Tumor Necrosis Factor-alpha/pharmacology , Cell Line, Tumor , Cells, Cultured , Colon/cytology , Colon/drug effects , Colon/metabolism , Epithelial Cells/metabolism , HT29 Cells , Humans , Interleukin-1/pharmacology , Interleukin-8/genetics , MAP Kinase Signaling System/drug effects , NF-KappaB Inhibitor alpha/metabolism , Phosphorylation/drug effects , p38 Mitogen-Activated Protein Kinases/metabolism
5.
Spinal Cord ; 55(11): 1016-1022, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28994415

ABSTRACT

STUDY DESIGN: A process evaluation of a clinical trial. OBJECTIVES: To describe the roles fulfilled by peer health coaches (PHCs) with spinal cord injury (SCI) during a randomized controlled trial research study called 'My Care My Call', a novel telephone-based, peer-led self-management intervention for adults with chronic SCI 1+ years after injury. SETTING: Connecticut and Greater Boston Area, MA, USA. METHODS: Directed content analysis was used to qualitatively examine information from 504 tele-coaching calls, conducted with 42 participants with SCI, by two trained SCI PHCs. Self-management was the focus of each 6-month PHC-peer relationship. PHCs documented how and when they used the communication tools (CTs) and information delivery strategies (IDSs) they developed for the intervention. Interaction data were coded and analyzed to determine PHC roles in relation to CT and IDS utilization and application. RESULTS: PHCs performed three principal roles: Role Model, Supporter, and Advisor. Role Model interactions included CTs and IDSs that allowed PHCs to share personal experiences of managing and living with an SCI, including sharing their opinions and advice when appropriate. As Supporters, PHCs used CTs and IDSs to build credible relationships based on dependability and reassuring encouragement. PHCs fulfilled the unique role of Advisor using CTs and IDSs to teach and strategize with peers about SCI self-management. CONCLUSION: The SCI PHC performs a powerful, flexible role in promoting SCI self-management among peers. Analysis of PHC roles can inform the design of peer-led interventions and highlights the importance for the provision of peer mentor training.


Subject(s)
Mentoring , Peer Group , Self-Management , Spinal Cord Injuries/psychology , Spinal Cord Injuries/rehabilitation , Communication , Humans , Interpersonal Relations , Learning , Process Assessment, Health Care , Qualitative Research , Social Support , Telephone
6.
Inflammation ; 40(5): 1726-1734, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28656529

ABSTRACT

IL-22 is known to induce intestinal epithelial cells (IECs) to produce the chemokine CXCL8. However, IECs exist in a cytokine network during mucosal inflammation, such that IL-22 must act in concert with potent pro-inflammatory cytokines like TNF-α and IL-1. Our studies show that IL-22 alone increased CXCL8 secretion from HT-29 cells, but the levels were minimal compared to that of the cells treated with TNF-α or IL-1 only. More significantly, co-stimulation with IL-22 and TNF-α enhanced both CXCL8 secretion and mRNA levels well over that of TNF-α stimulation alone. A similar enhancing effect was seen with IL-22- and IL-1-stimulated CXCL8 secretion. The enhancing effect of IL-22 on TNF-α-induced CXCL8 secretion was then determined to require the p38 MAPK, but not STAT1/3, PI3K, Akt, c-Jun N-terminal kinase, ERK, or IκBα. These experiments indicate that more significant effect of IL-22 on IECs responses may not be in inducing CXCL8 by itself, but in enhancing TNF-α- and IL-1-induced CXCL8 secretion to augment the contribution of IECs to local inflammatory responses.


Subject(s)
Epithelial Cells/metabolism , Interleukin-1/pharmacology , Interleukin-8/metabolism , Interleukins/pharmacology , Tumor Necrosis Factor-alpha/pharmacology , HT29 Cells , Humans , Intestines/cytology , Tumor Necrosis Factor-alpha/drug effects , p38 Mitogen-Activated Protein Kinases/physiology , Interleukin-22
7.
J Bacteriol ; 183(21): 6422-8, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11591687

ABSTRACT

The general stress response of Bacillus subtilis is controlled by the sigma(B) transcription factor, which is activated in response to diverse energy and environmental stresses. These two classes of stress are transmitted by separate signaling pathways which converge on the direct regulators of sigma(B), the RsbV anti-anti-sigma factor and the RsbW anti-sigma factor. The energy signaling branch involves the RsbP phosphatase, which dephosphorylates RsbV in order to trigger the general stress response. The rsbP structural gene lies downstream from rsbQ in a two-gene operon. Here we identify the RsbQ protein as a required positive regulator inferred to act in concert with the RsbP phosphatase. RsbQ bound RsbP in the yeast two-hybrid system, and a large in-frame deletion in rsbQ had the same phenotype as a null allele of rsbP-an inability to activate sigma(B) in response to energy stress. Genetic complementation studies indicated that this phenotype was not due to a polar effect of the rsbQ alteration on rsbP. The predicted rsbQ product is a hydrolase or acyltransferase of the alpha/beta fold superfamily, members of which catalyze a wide variety of reactions. Notably, substitutions in the presumed catalytic triad of RsbQ also abolished the energy stress response but had no detectable effect on RsbQ structure, synthesis, or stability. We conclude that the catalytic activity of RsbQ is an essential constituent of the energy stress signaling pathway.


Subject(s)
Bacillus subtilis/enzymology , Bacillus subtilis/genetics , Bacterial Proteins/metabolism , Gene Expression Regulation, Bacterial , Hydrolases/physiology , Saccharomyces cerevisiae Proteins , Sigma Factor/metabolism , Signal Transduction , Amino Acid Sequence , Catalysis , Energy Metabolism , Histidine/genetics , Histidine/physiology , Hydrolases/genetics , Kinetics , Models, Genetic , Molecular Sequence Data , Phosphoprotein Phosphatases/physiology , Point Mutation , Protein Phosphatase 2 , Protein Phosphatase 2C , Sequence Homology, Amino Acid , Serine/genetics , Serine/physiology , Trans-Activators/genetics , Trans-Activators/physiology
9.
Clin Exp Pharmacol Physiol ; 28(7): 510-7, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11422216

ABSTRACT

1. Previous reports indirectly implicate a neural mechanism for coronary constriction to centrally administered digitalis. However, autoregulatory changes in coronary resistance due to changes in arterial pressure may have influenced the interpretation of these studies. 2. We tested directly the hypothesis that cardiac sympathetic innervation is responsible for coronary constriction to ouabain by examining the effects of ouabain (intravenous (i.v.) and intracerebroventricular (i.c.v.)) before and after bilateral stellate ganglionectomy. 3. Cats were anaesthetized and instrumented for the measurement of heart rate, blood pressure and coronary blood flow velocity using an epicardial-attached suction Doppler probe. Animals were treated with atenolol and the effects of either i.v. or i.c.v. injections of ouabain were examined. 4. In seven cats treated with atenolol, i.v. ouabain (0.11 mg/kg) produced maximal increases in arterial pressure and coronary vascular resistance index (CVRI) of 66 +/- 7 mmHg and 37 +/- 9%, respectively. Following bilateral stellate ganglionectomy (n = 7), ouabain produced similar increases in arterial pressure (70 +/- 9 mmHg) and CVRI (39 +/- 7%). A higher dose of i.v. ouabain (1.1 mg/kg) produced maximal increases in arterial pressure (115 +/- 4 mmHg) and coronary resistance (86 +/- 14%) in intact cats (n = 6) that were similar to responses seen in cats in which stellate ganglionectomy had been performed (n = 6; arterial pressure 104 +/- 13 mmHg; coronary resistance 114 +/- 6%). The increases in coronary resistance to ouabain at both doses were significantly greater than increases in coronary resistance to passive elevation of arterial pressure during aortic constriction. Thus, autoregulation does not explain fully the coronary constriction to ouabain. 5. To further examine a central mechanism, i.c.v. perfusion with 0.3 mmol/L ouabain was performed in six cats, resulting in increases in arterial pressure (122 +/- 7 mmHg) and coronary resistance (58 +/- 14%). Similar increases in arterial pressure (117 +/- 16%) and coronary resistance (84 +/- 20%) were seen in separate studies (n = 6) following stellate ganglionectomy. 6. These results indicate that coronary constriction to ouabain does not require intact cardiac sympathetic innervation, but probably involves a direct or humorally mediated effect.


Subject(s)
Cardiotonic Agents/pharmacology , Coronary Vessels/drug effects , Heart/innervation , Ouabain/pharmacology , Sympathetic Nervous System , Vasoconstriction/drug effects , Animals , Blood Flow Velocity/drug effects , Blood Pressure/drug effects , Cardiotonic Agents/administration & dosage , Cats , Ganglionectomy , Heart Rate/drug effects , Injections, Intravenous , Injections, Intraventricular , Ouabain/administration & dosage , Stellate Ganglion , Vascular Resistance/drug effects
10.
Anesth Analg ; 91(5): 1250-5, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11049917

ABSTRACT

UNLABELLED: We examined the recovery characteristics of cisatracurium or rocuronium after bolus or prolonged infusion under either isoflurane or propofol anesthesia. Sixty patients undergoing neurosurgical procedures of at least 5 h were randomized to receive either isoflurane with fentanyl (Groups 1 and 2) or propofol and fentanyl (Groups 3 and 4) as their anesthetic. Groups 1 and 3 received cisatracurium 0.2 mg/kg IV bolus, spontaneously recovered, after which time an infusion was begun. Groups 2 and 4 received rocuronium 0.6 mg/kg IV, spontaneously recovered, and an infusion was begun. Before the end of surgery, the infusion was stopped and recovery of first twitch (T(1)), recovery index, clinical duration, and train-of-four (TOF) recovery was recorded and compared among groups by using appropriate statistical methods. Clinical duration was shorter for rocuronium compared with cisatracurium using either anesthetic. Cisatracurium T(1) 75% recovery after the infusion was shorter with propofol compared with isoflurane. Cisatracurium TOF 75% recovery was similar after either bolus or infusion, but rocuronium TOF 75% recovery after the infusion was delayed. Infusion rates decreased for cisatracurium but remained relatively constant for rocuronium regardless of the anesthetic used. Isoflurane enhances the effect of both muscle relaxants but prolonged cisatracurium recovery more than rocuronium. Of the two muscle relaxants studied, rocuronium's recovery was most affected by length of the infusion. Cisatracurium may be a more desired muscle relaxant for prolonged procedures because recovery was least affected by prolonged infusion. IMPLICATIONS: This study describes the effect of different anesthetic techniques on the recovery of two different muscle relaxants, cisatracurium and rocuronium, when administered as either a single bolus or prolonged infusion during neurosurgery. This study demonstrates the feasibility of using these relaxants for these prolonged procedures.


Subject(s)
Androstanols/administration & dosage , Anesthetics, Inhalation , Anesthetics, Intravenous , Atracurium/analogs & derivatives , Atracurium/administration & dosage , Isoflurane , Neuromuscular Blockade , Neuromuscular Blocking Agents/administration & dosage , Neuromuscular Nondepolarizing Agents/administration & dosage , Propofol , Female , Humans , Infusions, Intravenous , Injections, Intravenous , Male , Middle Aged , Muscle Contraction , Neurosurgical Procedures , Rocuronium
11.
Clin Cancer Res ; 6(7): 2941-50, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10914744

ABSTRACT

Tumor angiogenesis, the development of new blood vessels during malignant progression, is a regulated process that has both genetic and physiological controls. Physiologically, angiogenesis is stimulated by decreases in tissue oxygenation (i.e., hypoxia). We investigated the effect of hypoxia on the expression of two angiogenic factors reported to be genetically regulated by the p53 tumor suppressor gene: (a) the angiogenic inhibitor thrombospondin 1 (TSP-1); and (b) the angiogenic inducer vascular endothelial growth factor (VEGF). Analysis of rodent cells that differ in their p53 genotype (p53+/+ or p53-/-) indicated that in vitro exposure to hypoxia simultaneously suppressed TSP-1 and induced VEGF expression, regardless of the p53 genotype. On transformation of these cells with E1A and oncogenic H-ras, the basal level of TSP-1 expression was strongly diminished, whereas that of VEGF could still be induced by hypoxia. Consistent with these in vitro findings, sections of tumors derived from the transformed p53+/+ and p53-/- cells showed that VEGF protein overlapped with regions of hypoxia, whereas TSP-1 protein was below the limits of detection in tumor tissue. Using a panel of normal/immortalized and transformed human cells, it was found that the ability of hypoxia to inhibit TSP-1 expression depends on the cell type and/or the degree of transformation. In contrast, VEGF expression was induced by hypoxia in all of the human cell types examined. Together, these findings suggest that hypoxic and oncogenic signals could interact in the tumor microenvironment to inhibit TSP-1 and induce VEGF expression, promoting the switch to the angiogenic phenotype.


Subject(s)
Carcinoma, Squamous Cell/genetics , Cell Hypoxia , Endothelial Growth Factors/genetics , Gene Expression Regulation , Genes, p53 , Lymphokines/genetics , Thrombospondin 1/genetics , Uterine Cervical Neoplasms/genetics , Animals , Carcinoma, Squamous Cell/pathology , Cell Division , Cells, Cultured , Female , Humans , Mice , Mice, SCID , Transfection , Tumor Suppressor Protein p53/genetics , Uterine Cervical Neoplasms/pathology , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors , Xenograft Model Antitumor Assays
12.
Mol Microbiol ; 35(1): 180-8, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10632888

ABSTRACT

The sigmaB transcription factor of the bacterium Bacillus subtilis is activated by growth-limiting energy or environmental challenge to direct the synthesis of more than 100 general stress proteins. Although the signal transduction pathway that conveys these stress signals to sigmaB is becoming increasingly well understood, how environmental or energy stress signals enter this pathway remains unknown. We show here that two PP2C serine phosphatases - RsbP, which is required for response to energy stress, and RsbU, which is required for response to environmental stress - each converge on the RsbV regulator of sigmaB. According to the current understanding of sigmaB regulation, in unstressed cells the phosphorylated RsbV anti-anti-sigma is unable to complex the RsbW anti-sigma, which is then free to bind and inactivate sigmaB. We can now advance the model that either PP2C phosphatase, when triggered by its particular class of stress, can remove the phosphate from RsbV and thereby activate sigmaB. The action of the previously described RsbU is known to be controlled by dedicated upstream signalling components that are activated by environmental stress. The action of the RsbP phosphatase described here requires an energy stress, which we suggest is sensed, at least in part, by the PAS domain in the amino-terminal region of the RsbP phosphatase. In other bacterial signalling proteins, similar PAS domains and their associated chromophores directly sense changes in intracellular redox potential to control the activity of a linked output domain.


Subject(s)
Bacterial Proteins/metabolism , Phosphoprotein Phosphatases/metabolism , Saccharomyces cerevisiae Proteins , Sigma Factor , Transcription Factors/metabolism , Base Sequence , DNA Primers , Energy Metabolism , Operon , Phosphoprotein Phosphatases/chemistry , Phosphoprotein Phosphatases/genetics , Phosphorylation , Protein Phosphatase 2 , Protein Phosphatase 2C , Signal Transduction
13.
Am J Emerg Med ; 17(7): 638-41, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10597079

ABSTRACT

There has been a general trend in medicine towards greater sophistication in research design. In order to assess this trend in emergency medicine we compared the characteristics of abstracts presented at the 1974, 1983, 1989, and 1997 annual scientific meetings of academic emergency medicine. All 870 abstracts were reviewed by 1 of 3 investigators who determined research design attributes using a standardized classification scheme that has good interrater reliability. Over the last 25 years the following trends were noted: more surveys (0% v1% v3% v8%, P = 0.002), more randomized studies (0% v10% v12% v15%, P = 0.05), and more blinded studies (0% v7% v5% v11%, P = 0.01). Tests of statistical significance were reported with increasing frequency (8% v26% v59% v69%, P < 0.001) as were power calculations (0% v0% v1% v3%, P = 0.02). During the study period there were also increases in the median number of authors, proportion of foreign lead authors, and the proportion of studies involving human subjects. These results reflect considerable improvement in the degree of research design sophistication reported in selected abstracts of academic emergency medicine over the study period. Further strategies to assure continued enhancement of emergency medicine research should be explored.


Subject(s)
Abstracting and Indexing/trends , Emergency Medicine , Research Design/trends , Abstracting and Indexing/statistics & numerical data , Authorship , Congresses as Topic , Data Interpretation, Statistical , Female , Humans , Male , Observer Variation , Research Design/statistics & numerical data , Retrospective Studies , Societies, Medical , United States
14.
Am J Emerg Med ; 17(6): 540-3, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10530530

ABSTRACT

There has been a general trend in medicine toward greater sophistication in research design. To assess this trend in emergency medicine, we compared the characteristics of abstracts presented at the 1974, 1983, 1989, and 1997 annual scientific meetings of Academic Emergency Medicine. All 870 abstracts were reviewed by 1 of 3 investigators who determined research design attributes using a standardized classification scheme that has good interrater reliability. Over the last 25 years, the following trends were noted: more surveys (0% v1% v3% v8%, P=.002), more randomized studies (0% v10% v12% v15%, P=.05), and more blinded studies (0% v7% v5% v11%, P=.01). Tests of statistical significance were reported with increasing frequency (8% v26% v59% v 69%, P < .001), as were power calculations (0% v0% v1% v3%, P=.02). During the study period, there were also increases in the median number of authors, proportion of foreign lead authors, and the proportion of studies involving human subjects. These results reflect considerable improvement in the degree of research design sophistication reported in selected abstracts of academic emergency medicine over the study period. Further strategies to assure continued enhancement of emergency medicine research should be explored.


Subject(s)
Emergency Medicine , Research Design/trends , Bibliometrics , Female , Humans , Male , Randomized Controlled Trials as Topic/statistics & numerical data , Societies, Medical , United States
15.
N Engl J Med ; 341(8): 616-7; author reply 617-8, 1999 Aug 19.
Article in English | MEDLINE | ID: mdl-10475819
16.
Biochemistry ; 38(20): 6668-77, 1999 May 18.
Article in English | MEDLINE | ID: mdl-10350486

ABSTRACT

A comprehensive kinetic study of sulfite oxidase has been undertaken over the pH range 6.0-10.0, including conventional steady-state work as well as rapid kinetic studies of both the reaction of oxidized enzyme with sulfite and reduced enzyme with cytochrome c (III). A comparison of the pH dependence of kcat, kred, and kox indicates that kred is principally rate limiting above pH 7, but that below this pH the pH dependence of kcat is influenced by that of kox. The pH independence of kred is consistent with our previous proposal concerning the reaction mechanism, in which attack of the substrate lone pair of electrons on a Mo(VI)O2 unit initiates the catalytic sequence. The pH dependence of kred/Kdsulfite indicates that a group on the enzyme having a pKa of approximately 9.3 must be deprotonated for effective reaction of oxidized enzyme with sulfite, possibly Tyr 322, which from the crystal structure of the enzyme constitutes part of the substrate binding site. There is no evidence for the HSO3-/SO32- pKa of approximately 7 in the pH profile for kred/Kdsulfite, suggesting that enzyme is able to oxidize the two equally well. By contrast, kcat/Kmsulfite and kred/Kdsulfite exhibit distinct pH dependence (the former is bell-shaped, the latter sigmoidal), again consistent with the oxidative half-reaction contributing to the kinetic barrier to catalysis at low pH. The pH dependence of kcat/Km(cyt c) (reflecting the second-order rate of reaction of free enzyme with free cytochrome) is bell-shaped and closely resembles that of kox/Kd(cyt c), reflecting the importance of the oxidative half-reaction in the low substrate concentration regime. The pH profile for kox/Kd(cyt c) indicates that two groups with a pKa of approximately 8 are involved in the reaction of free reduced enzyme with cytochrome c, one of which must be deprotonated and the other protonated. These results are consistent with the known electrostatic nature of the interaction of cytochrome c with its physiological partners.


Subject(s)
Liver/enzymology , Oxidoreductases Acting on Sulfur Group Donors/metabolism , Animals , Binding Sites , Catalysis , Chickens , Cytochrome c Group/chemistry , Cytochrome c Group/metabolism , Hydrogen-Ion Concentration , Kinetics , Oxidation-Reduction , Oxidoreductases Acting on Sulfur Group Donors/chemistry , Substrate Specificity , Sulfites/chemistry , Sulfites/metabolism , Tyrosine/metabolism
17.
Gene ; 212(1): 111-8, 1998 May 28.
Article in English | MEDLINE | ID: mdl-9661670

ABSTRACT

The general stress response of the Gram-positive soil bacterium Bacillus subtilis is controlled by the sigma B transcription factor. sigma B activity is regulated by the newly discovered partner switching mechanism of signal transduction, which integrates the two different classes of challenges which posttranslationally activate sigma B: environmental stress and energy stress. Our investigation of a possible sigma B homologue in the related soil bacterium B. licheniformis had two goals. First, this study would contribute to understanding the distribution of the sigma B general stress system among Gram-positive bacteria. Second, a phylogenetic comparison of regulatory systems can supplement genetic and biochemical analysis by revealing conserved features that are critical for function. We report here that (1) B. licheniformis cells contain a protein that closely resembles B. subtilis sigma B in size and antigenic properties; (2) the level of this potential sigma B homologue rapidly increases following environmental or energy stress; and (3) the B. licheniformis genome encodes a homologue of the sigB general stress operon, including the sigma B structural gene and seven rsb regulatory genes. Based on these results, B. licheniformis possesses a general stress system likely regulated by two coupled partner switching modules that sense and integrate the two broad classes of activating stress signals.


Subject(s)
Bacillus/genetics , Bacterial Proteins/genetics , Heat-Shock Proteins/genetics , Sigma Factor/genetics , Transcription Factors/genetics , Amino Acid Sequence , Antibodies, Bacterial , Bacillus/immunology , Bacillus/metabolism , Bacillus subtilis/genetics , Bacillus subtilis/immunology , Bacillus subtilis/metabolism , Bacterial Proteins/immunology , Base Sequence , Conserved Sequence , Cross Reactions , DNA Primers/genetics , Genes, Bacterial , Heat-Shock Proteins/immunology , Molecular Sequence Data , Multigene Family , Operon , Phosphoprotein Phosphatases/genetics , Sequence Homology, Amino Acid , Sigma Factor/immunology , Signal Transduction , Species Specificity , Transcription Factors/immunology
18.
Neurology ; 50(2): 501-3, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9484380

ABSTRACT

Subsequent to publication of the NINDS t-PA Stroke Study results, we sought to determine the proportion of patients eligible for and receiving intravenous tissue plasminogen activator (t-PA) at an active acute stroke treatment center. Over a 12-month period there were 185 stroke code activations. Of these, 134 involved patients with ischemic stroke, and 48 of these (36%) were potentially eligible for treatment with t-PA by the time criterion (i.e., interval from stroke onset to hospital presentation < 3 hours). Nine of the 48 potentially eligible patients (19%) and 9 of 134 ischemic stroke patients (7%) overall received t-PA. In our patient population only a small proportion of all patients with acute ischemic stroke presently are eligible for treatment with t-PA.


Subject(s)
Brain Ischemia/drug therapy , Fibrinolytic Agents/therapeutic use , Tissue Plasminogen Activator/therapeutic use , Acute Disease , Alabama , Brain Ischemia/diagnosis , Fibrinolytic Agents/administration & dosage , Hospital Bed Capacity, 300 to 499 , Hospitalization , Hospitals, University , Humans , Infusions, Intravenous , Patient Selection , Time Factors , Tissue Plasminogen Activator/administration & dosage
20.
Am Ind Hyg Assoc J ; 58(10): 704-12, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9342830

ABSTRACT

Sensitivity of olfaction (smell) and chemesthesis (irritation) was evaluated for 2-propanone (acetone) and 1-butanol in acetone-exposed workers (AEW; N = 32) during a workday and unexposed subjects (microES; N = 32). Irritation sensitivity was assessed using a method that relies on the ability of individuals to localize irritants on the body. When a volatile compound is inhaled into one nostril and air into the other, the stimulated side can be determined (lateralized) only after the concentration reaches a level that stimulates the trigeminal nerve (irritation); compounds stimulating olfaction alone cannot be lateralized. Intranasal lateralization thresholds offer an objective measure of sensory irritation elicited by volatile compounds. Test results indicated that neither olfactory nor lateralization thresholds for butanol differed between AEW and microES. Olfactory thresholds to acetone in AEW (855 ppm) were elevated relative to those of microES (41 ppm), as were lateralization thresholds (36,669 ppm and 15,758 ppm, respectively). Within AEW, level of occupational exposure was not correlated with thresholds. Other measures revealed that microES used more irritation descriptors than did AEW on trials where the acetone concentration was below the lateralization threshold. This is noteworthy because microES received lower concentrations of acetone to evaluate than did AEW. These results suggest that exposures to acetone induce changes in acetone sensitivity that are specific to acetone. The acetone concentrations eliciting sensory irritation using the lateralization technique were all well above current occupational exposure standards. The current study indicates that acetone is a weak sensory irritant and that sensory adaptation is an important factor affecting its overall irritancy.


Subject(s)
Acetone/adverse effects , Irritants/adverse effects , Nasal Mucosa/drug effects , Occupational Exposure/adverse effects , Sensory Thresholds/drug effects , 1-Butanol/pharmacology , Adult , Analysis of Variance , Case-Control Studies , Female , Humans , Male , Middle Aged , Smell/drug effects , Statistics, Nonparametric
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