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1.
Nurs Educ Perspect ; 45(4): 219-224, 2024.
Article in English | MEDLINE | ID: mdl-38265081

ABSTRACT

AIM: The purpose of this scoping review was to examine the extent, range, and nature of RN-to-BS nursing education research. BACKGROUND: The state of nursing education science specific to RN-to-BS education is not available. METHOD: Scoping review methodology was used to identify categories and types of published research related to RN-to-BS nursing education. RESULTS: Eight categories were identified across the 41 articles that met the inclusion criteria: teaching strategies ( n = 11), curriculum ( n = 9), enrollment/retention ( n = 8), benefits of a bachelor's degree ( n = 4), student characteristics ( n = 3), professional values ( n = 2), role transition ( n = 2), and faculty/student expectations ( n = 2). CONCLUSION: Opportunities exist for researchers to study RN-BS students and faculty to better support evidence-based teaching practices and faculty development needs relevant for the increasingly hybrid and online student populations.


Subject(s)
Education, Nursing, Baccalaureate , Nursing Education Research , Humans , Curriculum , Students, Nursing/psychology , Faculty, Nursing
2.
Vet Radiol Ultrasound ; 61(4): 409-416, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32436257

ABSTRACT

Xanthogranulomatous disease is a rare condition, which can be caused by infection, inflammation, hemorrhage, immunologic disease, or inherited lysosomal disorders. It is characterized by non-intracellular lipid and cholesterol deposits among an inflammatory infiltrate of vacuolated macrophages and giant cells. The diagnosis of xanthogranulomatous disease is challenging, with nonspecific imaging findings often misinterpreted as aggressive neoplastic processes in humans. In this retrospective case series study, we describe the diagnostic imaging characteristics of a disseminated xanthogranulomatous condition identified in five eclectus parrots (Eclectus roratus). Decreased serosal detail and celomic distension were present in all three birds radiographed, with multifocal variably sized celomic mineralization (3/3 birds), and extracelomic mineralized masses (1/3 birds). Celomic effusion with foci of celomic mineralization and hepatomegaly were identified in all birds (3/3) imaged with ultrasound. Finally, a mineralized mural ventricular mass was present in one of three patients imaged with CT, multifocal celomic mineralization with moderate to severe celomic effusion in two of three patients, diffuse severe proventricular and intestinal dilation in all three patients, and atherosclerosis of the major arterial trunks in all three patients. Veterinary radiologists should be aware of this inflammatory condition in birds, especially in eclectus parrots, and should be able to recognize the imaging features of xanthogranulomatous inflammation.


Subject(s)
Bird Diseases/diagnostic imaging , Granuloma/veterinary , Parrots , Xanthomatosis/veterinary , Animals , Female , Granuloma/diagnostic imaging , Inflammation/veterinary , Retrospective Studies , Xanthomatosis/diagnostic imaging
3.
Pediatr Transplant ; 22(3): e13165, 2018 05.
Article in English | MEDLINE | ID: mdl-29441651

ABSTRACT

Children undergoing LSBPTx are at increased risk of IPI due to splenectomy. We aimed to describe the clinical features and outcomes of IPI in pediatric LSBPTx recipients. Between 2008 and 2016, 122 LSBPTx children at our center were retrospectively reviewed. Nine patients had 12 episodes of IPI; the median age at first infection was 3.5Ā years (range: 1.5-7.1Ā years). The median time from transplant to first infection was 3Ā years (range: 0.8-5.8Ā years). Clinical presentation included as follows: pneumonia (nĀ =Ā 1), bacteremia/sepsis (nĀ =Ā 7), pneumonia with sepsis (nĀ =Ā 1), meningitis with sepsis (nĀ =Ā 2), pneumonia and meningitis with sepsis (nĀ =Ā 1). The overall risk for IPI was 7.4% or 0.9% per year. The mortality rate was 22%. Seven (78%) children had received at least one dose of PCV13, four (44%) patients had received 23-valent pneumococcal polysaccharide vaccine prior to IPI. All patients were on oral penicillin prophylaxis. In conclusion, despite partial or complete pneumococcal immunization and reported antimicrobial prophylaxis, IPI in LSBPTx children can have a fatal outcome. Routine monitoring of pneumococcal serotype antibodies to determine the timing for revaccination might be warranted to ensure protective immunity in these transplant recipients.


Subject(s)
Intestine, Small/transplantation , Liver Transplantation , Pancreas Transplantation , Pneumococcal Infections/diagnosis , Pneumococcal Infections/etiology , Postoperative Complications/diagnosis , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Male , Pneumococcal Infections/epidemiology , Pneumococcal Infections/therapy , Postoperative Complications/epidemiology , Postoperative Complications/therapy , Retrospective Studies , Splenectomy , Treatment Outcome
4.
Can Vet J ; 58(3): 293-295, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28246420

ABSTRACT

An 8-year-old cat was presented with vomiting and weight loss. Histopathology and cytology revealed systemic mastocytosis, a rare condition and a clinical challenge. This case emphasizes the significance of cytological evaluation of smears in diagnosis of mastocytosis and in confirmation in biopsy specimens.


Signification de l'Ć©valuation d'un frottis cytologique dans le diagnostic d'une mastocytose systĆ©mique chez un chat(Felis catus)associĆ©e Ć  une tumeur des mastocytes splĆ©niques. Un chat Ć¢gĆ© de huit ans a Ć©tĆ© prĆ©sentĆ© avec des vomissements et une perte de poids. L'histopathologie et la cytologie ont rĆ©vĆ©lĆ© une mastocytose systĆ©mique, une affection rare et difficile sur le plan clinique. Ce cas met en lumiĆØre l'importance de l'Ć©valuation cytologique des frottis pour le diagnostic de la mastocytose et la confirmation pour les spĆ©cimens de biopsie.(Traduit par Isabelle ValliĆØres).


Subject(s)
Cat Diseases/diagnosis , Mastocytosis, Systemic/veterinary , Splenic Neoplasms/veterinary , Animals , Cat Diseases/blood , Cat Diseases/pathology , Cats , Female , Mast Cells/pathology , Mastocytosis, Systemic/blood , Mastocytosis, Systemic/diagnosis , Splenic Neoplasms/blood , Splenic Neoplasms/diagnosis , Splenic Neoplasms/pathology
5.
Pain Manag Nurs ; 13(3): 139-49, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22929601

ABSTRACT

This study examined the effects of oral sucrose as an analgesic agent during routine immunization for infants at 2, 4, and 6 months of age. AĀ sample of 113 healthy infants were recruited from three ambulatory clinics and randomly assigned to one of three treatment groups. Infants were given 2 mL orally of either 50% sucrose, 75% sucrose, orĀ sterile water 2 minutes before administration of immunizations. No significant difference was found among the different age groups with the different treatments for pain as measured with the FLACC scores and crying time. Consolability factors are felt to have some influence.


Subject(s)
Acute Pain/drug therapy , Acute Pain/nursing , Analgesics/administration & dosage , Immunization/adverse effects , Pediatric Nursing/methods , Sucrose/administration & dosage , Administration, Oral , Crying , Female , Humans , Infant , Male , Pacifiers , Pain Management/methods , Pain Management/nursing , Water/administration & dosage
6.
Perm J ; 242020.
Article in English | MEDLINE | ID: mdl-31905341

ABSTRACT

INTRODUCTION: Millions of adults worldwide use low-dose aspirin for secondary prevention of heart disease. Results of randomized trials indicate that regular use of low-dose aspirin may reduce the risk of colorectal cancer by more than 20%, leading to speculation of its chemoprevention role for high-risk groups. Little is known, however, about the use of aspirin in our community. OBJECTIVE: To determine aspirin use and therapy compliance (never or rarely missing a dose) and to assess whether patients in our community are aware of its anticancer effect. METHODS: Observational study. Prospective data were collected during a 1-year period from patients in our general surgical clinic regarding aspirin use, comorbidities, adverse effects, and awareness of anticancer effect. Statistical analysis was performed. RESULTS: Among aspirin users (n = 137), the mean age was 65.8 years. Most (76.6%) received an 81-mg daily dose of aspirin. Compliance was 25.6% and was significantly associated with diabetes mellitus (p = 0.0028). Only 9.5% were aware of the medication's anticancer effect. Among nonusers (n = 383), the mean age was 53.3 years, a significant difference vs that of aspirin users (p < 0.001). Only 4.7% of nonusers knew of the anticancer effect. Nonusers were more likely to be women (p = 0.0005), younger than age 40 years (p < 0.0001), and have comorbidities or polypharmacy (p = 0.002). No significant difference was found between groups in anticoagulants use, nonsteroidal anti-inflammatory drug use, and smoking. CONCLUSION: Knowledge of aspirin's anticancer effect is low. More research is required to understand why aspirin compliance is also low.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Aspirin/administration & dosage , Colorectal Neoplasms/prevention & control , Health Knowledge, Attitudes, Practice , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Aspirin/adverse effects , Comorbidity , Dose-Response Relationship, Drug , Female , Humans , Male , Medication Adherence , Middle Aged , Polypharmacy , Prospective Studies , Sex Factors , Young Adult
7.
Dev Cell ; 4(6): 865-77, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12791271

ABSTRACT

The migration of epithelial layers requires specific and coordinated organization of the cells at the leading edge of the sheet. Mice that are conditionally deleted for the c-jun protooncogene in epidermis are born at expected frequencies, but with open eyes and with defects in epidermal wound healing. Keratinocytes lacking c-Jun are unable to migrate or elongate properly in culture at the border of scratch assays. Histological analyses in vitro and in vivo demonstrate an inability to activate EGF receptor at the leading edge of wounds, and we demonstrate that this can be rescued by supplementation with conditioned medium or the EGF receptor ligand HB-EGF. Lack of c-Jun prevents EGF-induced expression of HB-EGF, indicating that c-jun controls formation of the epidermal leading edge through its control of an EGF receptor autocrine loop.


Subject(s)
Epidermis/growth & development , ErbB Receptors/metabolism , Genes, jun/physiology , Animals , Cell Division , Cell Movement , Cells, Cultured , Epidermal Cells , Epidermal Growth Factor/metabolism , Epidermis/injuries , Eyelids/abnormalities , Eyelids/embryology , Gene Deletion , Heparin-binding EGF-like Growth Factor , Intercellular Signaling Peptides and Proteins , Keratinocytes/cytology , Keratinocytes/physiology , Keratins/metabolism , Mice , Mice, Transgenic , Mutation , Phosphoprotein Phosphatases , Proliferating Cell Nuclear Antigen/metabolism , Time Factors , Transcription Factor AP-1/metabolism
8.
Leuk Res ; 31(3): 341-52, 2007 Mar.
Article in English | MEDLINE | ID: mdl-16996129

ABSTRACT

Clinical studies have suggested that bisphosphonates may prolong the survival of sub-sets of myeloma patients. Newer nitrogen containing bisphosphonates such as zoledronate act, at least in part, by inhibiting farnesyl diphosphate synthase and subsequent protein prenylation, furthermore, limited data suggests that zoledronate exerts a direct anti-tumour effect against human myeloma cell lines. We therefore investigated the anti-myeloma potential of zoledronate in comparison to, and in combination with, two other inhibitors of the mevalonate pathway: the HMGCoA reductase inhibitor fluvastatin and the farnesyl transferase inhibitor SCH66336. We found that fluvastatin was able to inhibit the proliferation of myeloma cells more effectively than zoledronate or SCH66336 and that combinations of zoledronate and fluvastatin, but not zoledronate and SCH66336 acted synergistically. Our data indicated that the anti-proliferative effect of mevalonate pathway inhibitors is mediated principally via prevention of geranylgeranylation and is the result of both cell cycle arrest and apoptosis induction. Microarray and quantitative real-time PCR analyses further demonstrated that genes related to apoptosis, cell cycle control, and the mevalonate pathway were particularly affected by zoledronate and fluvastatin, and that some of these genetic effects were synergistic. We conclude that the mechanisms of geranylgeranylation inhibition mediated anti-myeloma effects warrant further evaluation and may provide novel targets for future therapeutic development.


Subject(s)
Diphosphonates/pharmacology , Fatty Acids, Monounsaturated/pharmacology , Imidazoles/pharmacology , Indoles/pharmacology , Mevalonic Acid/metabolism , Multiple Myeloma/drug therapy , Multiple Myeloma/metabolism , Piperidines/pharmacology , Pyridines/pharmacology , Apoptosis/drug effects , Apoptosis Regulatory Proteins/antagonists & inhibitors , Apoptosis Regulatory Proteins/biosynthesis , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Diphosphonates/therapeutic use , Drug Screening Assays, Antitumor , Fatty Acids, Monounsaturated/therapeutic use , Fluvastatin , Humans , Imidazoles/therapeutic use , Indoles/therapeutic use , Mevalonic Acid/antagonists & inhibitors , Piperidines/therapeutic use , Pyridines/therapeutic use , Structure-Activity Relationship , Zoledronic Acid
9.
Mol Cell Biol ; 22(8): 2515-23, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11909946

ABSTRACT

Hypoxia (low-oxygen tension) is an important physiological stress that influences responses to a wide range of pathologies, including stroke, infarction, and tumorigenesis. Prolonged or chronic hypoxia stimulates expression of the stress-inducible transcription factor gene c-jun and transient activation of protein kinase and phosphatase activities that regulate c-Jun/AP-1 activity. Here we describe evidence obtained by using wild-type and HIF-1 alpha nullizygous mouse embryonic fibroblasts (mEFs) that the induction of c-jun mRNA expression and c-Jun phosphorylation by prolonged hypoxia are completely dependent on the presence of the oxygen-regulated transcription factor hypoxia-inducible factor 1 alpha (HIF-1 alpha). In contrast, transient hypoxia induced c-jun expression in both types of mEFs, showing that the early or rapid induction of this gene is independent of HIF-1 alpha. These findings indicate that the c-jun gene has a biphasic response to hypoxia consisting of inductions that depend on the degree or duration of exposure. To more completely define the relationship between prolonged hypoxia and c-Jun phosphorylation, we used mEFs from mice containing inactivating mutations of critical phosphorylation sites in the c-Jun N-terminal region (serines 63 and 73 or threonines 91 and 93). Exposure of these mEFs to prolonged hypoxia demonstrated an absolute requirement for N-terminal sites for HIF-1 alpha-dependent phosphorylation of c-Jun. Taken together, these findings suggest that c-Jun/AP-1 and HIF-1 cooperate to regulate gene expression in pathophysiological microenvironments.


Subject(s)
Cell Hypoxia/genetics , Cell Hypoxia/physiology , Proto-Oncogene Proteins c-jun/genetics , Proto-Oncogene Proteins c-jun/metabolism , Transcription Factor AP-1/metabolism , Transcription Factors/metabolism , Animals , Binding Sites/genetics , Cell Line , Gene Expression Regulation , Hypoxia-Inducible Factor 1, alpha Subunit , Mice , Mice, Knockout , Mutagenesis, Site-Directed , Phosphorylation , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transcription Factors/deficiency , Transcription Factors/genetics
11.
J Gastrointest Surg ; 7(8): 1069-72, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14675717

ABSTRACT

Patients with Crohn's disease are at high risk for recurrent disease and often undergo multiple operations. Our aims were to evaluate surgical management and outcome of patients with Crohn's disease who develop short bowel syndrome (SBS) and to identify factors leading to this complication. We reviewed the records of 170 adult patients with SBS evaluated over a 20-year period. Thirty (18%) had Crohn's disease. SBS was defined as an intestinal remnant less than 180 cm with associated malabsorption. There were 20 women and 10 men ranging in age from 18 to 62 years. Eighteen (60%) presented initially with ileocolonic disease, seven (23%) with colonic disease, and five (17%) with small intestinal disease. The interval from initial diagnosis to development of SBS ranged from 2 to 32 years, with 21 patients (71%) having an interval greater than 15 years. The number of resections leading to SBS varied from 2 to 12 with 24 patients (80%) having four or fewer resections. Nineteen patients (63%) had an ostomy. Small intestinal remnant length was less than 60 cm in 10 patients, 60 to 120 cm in six patients, and greater than 120 cm in 14 patients. Only one patient underwent stricturoplasty before developing SBS. Five patients were initially diagnosed as having ulcerative colitis and underwent a pouch procedure, which was subsequently resected. Twenty patients (67%) required parenteral nutrition. Three patients have undergone reversed intestinal segment to slow intestinal transit. Two patients underwent intestinal transplantation. Two patients have died: one from parenteral nutrition-related liver failure and the other after intestinal transplantation. Crohn's disease remains a common cause of SBS. Aggressive resectional therapy, surgical complications, and errors in initial diagnosis contribute to development of SBS in these patients. Selected patients are candidates for surgical therapy for SBS.


Subject(s)
Crohn Disease/surgery , Diagnostic Errors , Digestive System Surgical Procedures/adverse effects , Parenteral Nutrition , Short Bowel Syndrome/therapy , Adolescent , Adult , Crohn Disease/complications , Crohn Disease/diagnosis , Female , Humans , Intestines/physiopathology , Intestines/surgery , Male , Middle Aged , Recurrence , Reoperation , Retrospective Studies , Short Bowel Syndrome/etiology , Treatment Outcome
12.
Prog Transplant ; 14(4): 290-6; quiz 297-8, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15663014

ABSTRACT

Over the last 3 decades, there has been significant improvement in the survival and quality of life of patients who require home parenteral nutrition; however, parenteral nutrition remains costly, is associated with multiple complications, and does not promote the function of the remaining bowel. Intestinal rehabilitation refers to the process of restoring enteral autonomy and decreasing dependence on parenteral nutrition by utilizing dietary, pharmacological, and, occasionally, surgical interventions. A major focus of research has been to identify a trophic factor that will enhance adaptation of the remaining gastrointestinal tract following massive gut resection and allow enteral autonomy. Whether intestinal rehabilitation occurs as the result of increased intestinal adaptation or as the result of a comprehensive approach to care has yet to be determined. This article reviews intestinal failure as the result of short-bowel syndrome and the management strategy of an intestinal rehabilitation program in the care of these patients.


Subject(s)
Short Bowel Syndrome/physiopathology , Short Bowel Syndrome/rehabilitation , Adaptation, Biological , Humans , Nutrition Assessment , Patient Education as Topic
13.
J Biomed Mater Res B Appl Biomater ; 92(1): 78-85, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19802834

ABSTRACT

Polyethylene (PE) debris has been well studied in clinical retrievals and laboratory wear simulations of total hip replacements. However, little is known about PE debris from total knee replacements. In this study, we investigated the effects of crosslinking PE bearings and alternate counterface material. Mildly (35 kGy) and highly (70 kGy) crosslinked PE were studied in combination with CoCr and zirconia femoral counterfaces. Wear debris was isolated and its morphology characterized. Except for changes in PE debris size with the zirconia bearings, there were no morphological changes greater than 10%. The average submicron volume fraction decreased from about 65% to 45% with both increased crosslinking and changing counterface material from CoCr to zirconia. The averaged number of generated particles decreased by approximately fourfold with increased crosslinking and threefold with changing counterface material from CoCr to zirconia. This showed that the degree of PE crosslinking and the choice of counterface material were important factors in the PE wear debris production in total knee simulator replacements.


Subject(s)
Biocompatible Materials , Knee , Models, Biological , Polyethylene , Humans , Microscopy, Electron, Scanning
14.
Bioorg Med Chem Lett ; 16(17): 4554-8, 2006 Sep 01.
Article in English | MEDLINE | ID: mdl-16784854

ABSTRACT

As a continuation of our efforts to discover novel apoptosis inducers as anticancer agents using a cell-based caspase HTS assay, 2-phenyl-oxazole-4-carboxamide derivatives were identified. The structure-activity relationships of this class of molecules were explored. Compound 1k, with EC(50) of 270 nM and GI(50) of 229 nM in human colorectal DLD-1 cells, was selected and demonstrated the ability to cleave PARP and displayed DNA laddering, the hallmarks of apoptosis. Compound 1k showed 63% tumor growth inhibition in human colorectal DLD-1 xenograft mouse model at 50 mpk, bid.


Subject(s)
Amides/chemistry , Amides/pharmacology , Apoptosis/drug effects , Oxazoles/chemistry , Oxazoles/pharmacology , Amides/chemical synthesis , Animals , Cell Line, Tumor , Female , Humans , Mice , Molecular Structure , Oxazoles/chemical synthesis , Structure-Activity Relationship , Xenograft Model Antitumor Assays
15.
Echocardiography ; 20(2): 183-4, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12848685

ABSTRACT

Identical bicuspid valve anomalies were found in monozygotic twins. Screening echocardiography should be considered for first-degree relatives of patients with bicuspid aortic valve.


Subject(s)
Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/genetics , Aortic Valve/abnormalities , Diseases in Twins/genetics , Adult , Echocardiography, Doppler , Female , Follow-Up Studies , Heart Defects, Congenital/diagnostic imaging , Humans , Mitral Valve/abnormalities , Risk Assessment , Twins, Monozygotic
16.
J Biol Chem ; 279(5): 3635-42, 2004 Jan 30.
Article in English | MEDLINE | ID: mdl-14593104

ABSTRACT

The predicted TM10 transmembrane sequence, (4844)IIFDITFFFFVIVILLAIIQGLII(4867), has been proposed to be the pore inner helix of the ryanodine receptor (RyR) and to play a crucial role in channel activation and gating, as with the inner helix of bacterial potassium channels. However, experimental evidence for the involvement of the TM10 sequence in RyR channel activation and gating is lacking. In the present study, we have systematically investigated the effects of mutations of each residue within the 24-amino acid TM10 sequence of the mouse cardiac ryanodine receptor (RyR2) on channel activation by caffeine and Ca(2+). Intracellular Ca(2+) release measurements in human embryonic kidney 293 cells expressing the RyR2 wild type and TM10 mutants revealed that several mutations in the TM10 sequence either abolished caffeine response or markedly reduced the sensitivity of the RyR2 channel to activation by caffeine. By assessing the Ca(2+) dependence of [(3)H]ryanodine binding to RyR2 wild type and TM10 mutants we also found that mutations in the TM10 sequence altered the sensitivity of the channel to activation by Ca(2+) and enhanced the basal activity of [(3)H]ryanodine binding. Furthermore, single I4862A mutant channels exhibited considerable channel openings and altered gating at very low concentrations of Ca(2+). Our data indicate that the TM10 sequence constitutes an essential determinant for channel activation and gating, in keeping with the proposed role of TM10 as an inner helix of RyR. Our results also shed insight into the orientation of the TM10 helix within the RyR channel pore.


Subject(s)
Calcium/chemistry , Cell Membrane/metabolism , Myocardium/metabolism , Ryanodine Receptor Calcium Release Channel/physiology , Amino Acid Sequence , Caffeine/pharmacology , Calcium/metabolism , Cell Line , DNA/chemistry , Dose-Response Relationship, Drug , Humans , Molecular Sequence Data , Mutagenesis, Site-Directed , Mutation , Potassium Channels/chemistry , Protein Binding , Protein Structure, Secondary , Protein Structure, Tertiary , Ryanodine Receptor Calcium Release Channel/chemistry , Time Factors , Transfection
17.
J Biol Chem ; 278(51): 51557-65, 2003 Dec 19.
Article in English | MEDLINE | ID: mdl-14557272

ABSTRACT

Despite the pivotal role of ryanodine in ryanodine receptor (RyR) research, the molecular basis of ryanodine-RyR interaction remains largely undefined. We investigated the role of the proposed transmembrane helix TM10 in ryanodine interaction and channel function. Each amino acid residue within the TM10 sequence, 4844IIFDITFFFFVIVILLAIIQGLII4867, of the mouse RyR2 was mutated to either alanine or glycine. Mutants were expressed in human embryonic kidney 293 cells, and their properties were assessed. Mutations D4847A, F4850A, F4851A, L4858A, L4859A, and I4866A severely curtailed the release of intracellular Ca2+ in human embryonic kidney 293 cells in response to extracellular caffeine and diminished [3H]ryanodine binding to cell lysates. Mutations F4846A, T4849A, I4855A, V4856A, and Q4863A eliminated or markedly reduced [3H]ryanodine binding, but cells expressing these mutants responded to extracellular caffeine by releasing stored Ca2+. Interestingly these two groups of mutants, each with similar properties, are largely located on opposite sides of the predicted TM10 helix. Single channel analyses revealed that mutation Q4863A dramatically altered the kinetics and apparent affinity of ryanodine interaction with single RyR2 channels and abolished the effect of ryanodol, an analogue of ryanodine, whereas the single channel conductance of the Q4863A mutant and its responses to caffeine, ATP, and Mg2+ were comparable to those of the wild type channels. Furthermore the effect of ryanodine on single Q4863A mutant channels was influenced by the transmembrane holding potential. Together these results suggest that the TM10 sequence and in particular the Q4863 residue constitute an important determinant of ryanodine interaction.


Subject(s)
Glutamine , Membrane Proteins/physiology , Ryanodine Receptor Calcium Release Channel/metabolism , Ryanodine Receptor Calcium Release Channel/physiology , Ryanodine/metabolism , Amino Acid Sequence , Amino Acid Substitution , Animals , Cloning, Molecular , Electrophysiology , Membrane Proteins/chemistry , Membrane Proteins/metabolism , Mice , Mutagenesis, Site-Directed , Protein Binding , Ryanodine Receptor Calcium Release Channel/chemistry , Transfection
18.
Am J Physiol Lung Cell Mol Physiol ; 283(5): L1002-10, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12376353

ABSTRACT

Surfactant proteins-A and -D (SP-A and SP-D) are members of the collectin protein family. Mice singly deficient in SP-A and SP-D have distinct phenotypes. Both have altered inflammatory responses to microbial challenges. To further investigate the functions of SP-A and SP-D in vivo, we developed mice deficient in both proteins by sequentially targeting the closely linked genes in embryonic stem cells using graded resistance to G-418. There is a progressive increase in bronchoalveolar lavage phospholipid, protein, and macrophage content through 24 wk of age. The macrophages from doubly deficient mice express high levels of the matrix metalloproteinase MMP-12 and develop intense but patchy lung inflammation. Stereological analysis demonstrates significant air space enlargement and reduction in alveolar septal tissue per unit volume, consistent with emphysema. These changes qualitatively resemble the lung pathology seen in SP-D-deficient mice. These doubly deficient mice will be useful in dissecting the potential overlap in function between SP-A and SP-D in host defense.


Subject(s)
Emphysema/genetics , Lipoid Proteinosis of Urbach and Wiethe/genetics , Pulmonary Surfactant-Associated Protein A/deficiency , Pulmonary Surfactant-Associated Protein D/deficiency , Animals , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Chromosome Mapping , Disease Progression , Emphysema/pathology , Gene Expression Regulation , Lipoid Proteinosis of Urbach and Wiethe/pathology , Macrophages, Alveolar/pathology , Matrix Metalloproteinase 12 , Metalloendopeptidases/genetics , Metalloendopeptidases/metabolism , Mice , Mice, Knockout , Phospholipids/analysis , Pulmonary Surfactant-Associated Protein A/genetics , Pulmonary Surfactant-Associated Protein A/physiology , Pulmonary Surfactant-Associated Protein D/genetics , Pulmonary Surfactant-Associated Protein D/physiology , RNA, Messenger/genetics , Transcription, Genetic
19.
J Pediatr Gastroenterol Nutr ; 34(2): 194-8, 2002 02.
Article in English | MEDLINE | ID: mdl-11840039

ABSTRACT

BACKGROUND: Proton pump inhibitors such as omeprazole are increasingly used to prevent stress-related gastric bleeding in critically ill patients. In this investigation, the acid-suppressive potency of omeprazole was assessed in one at-risk group, pediatric patients undergoing liver or intestinal transplantation, or both. METHODS: Twenty-two patients ranging in age from 0.9 to 108 months (23.8 +/- 6.5) underwent isolated liver (n = 10) or intestinal (11 with composite liver allografts) transplantation. Omeprazole was delivered in bicarbonate suspension through a nasogastric tube. Therapy was started after surgery at 0.5 mg/kg every 12 hours. Gastric pH monitoring was performed approximately 2 days later. RESULTS: For the entire group, mean gastric pH equaled 6.1 +/- 0.3, the same in recipients of isolated liver and intestinal allografts. Twelve of the 22 patients demonstrated a discontinuous omeprazole effect, that is, dissipation of acid reduction before the next dose. Five of the 12 patients with discontinuous omeprazole effect had mean gastric pH of less than 5 (3.9 +/- 0.4). In 4 of these 5, the omeprazole dosing interval was shortened to every 8 or every 6 hours, resulting in an increase in mean pH to 6.6 +/- 0.2 ( P < 0.01). In the remaining 10 of 22 patients, acid suppression was uninterrupted until the next dose. No patient experienced bleeding attributable to gastric erosion. CONCLUSION: Omeprazole suspended in sodium bicarbonate is an effective acid-suppressing agent in pediatric recipients of liver or intestinal transplant, or both. A dosage of 0.5 mg/kg every 12 hours is sufficient for most patients, but dosing every 6 to 8 hours is required to assure maximal acid suppression in all.


Subject(s)
Anti-Ulcer Agents/therapeutic use , Gastric Acid/metabolism , Omeprazole/therapeutic use , Stomach Ulcer/prevention & control , Anti-Ulcer Agents/administration & dosage , Anti-Ulcer Agents/pharmacology , Child , Child, Preschool , Critical Illness , Dose-Response Relationship, Drug , Female , Gastric Acidity Determination , Humans , Hydrogen-Ion Concentration , Infant , Infant, Newborn , Intestines/transplantation , Intubation, Gastrointestinal , Liver Transplantation , Male , Omeprazole/administration & dosage , Omeprazole/pharmacology , Peptic Ulcer Hemorrhage/etiology , Peptic Ulcer Hemorrhage/prevention & control , Postoperative Complications/prevention & control , Proton Pump Inhibitors , Stomach/chemistry , Stomach/drug effects , Stomach Ulcer/complications , Time Factors
20.
Plant J ; 33(5): 867-74, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12609028

ABSTRACT

MADS-domain-containing transcription factors comprise a large family of regulators that have diverse roles in plant development, including the regulation of flowering time. AGAMOUS-LIKE 20/SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) and FRUITFUL act to promote flowering, whereas FLOWERING LOCUS C (FLC), FLOWERING LOCUS M/MADS AFFECTING FLOWERING1, and SHORT VEGETATIVE PHASE are inhibitors of flowering. Here we report that AGAMOUS-LIKE 24 (AGL24) also plays a role in the regulation of flowering time. agl24 mutants are late flowering and overexpression of AGL24 causes early flowering in wild-type and late-flowering-mutant backgrounds. The effect of AGL24 overexpression is most pronounced in autonomous-pathway-mutant and FRIGIDA-containing backgrounds. The behavior of AGL24 is most similar to that of SOC1. Like SOC1, AGL24 mRNA levels are upregulated by vernalization. Unlike SOC1, however, AGL24 mRNA levels are not affected by FLC, and therefore AGL24 may represent an FLC-independent target of the vernalization pathway. There is also evidence for cross-talk between AGL24 and SOC1. When overexpressed, SOC1 and AGL24 are able to upregulate each other's expression. Thus, AGL24 represents another component in a network of MADS-domain-containing transcription factors that regulate flowering time.


Subject(s)
Arabidopsis/metabolism , Flowers/metabolism , Gene Expression Regulation, Plant , Up-Regulation , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Flowers/genetics , MADS Domain Proteins/genetics , MADS Domain Proteins/metabolism , Mutation/genetics , Phenotype
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