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Biomedical subjects

J McCormick

Publications and source records attributed to J McCormick.

At least 19 recordsLinked to original sources
PubMed2007

Paediatric Northern Score centile charts for the chest radiograph in cystic fibrosis.

AIM: To create the first national centile charts for the chest radiograph Northern Score using the UK Cystic Fibrosis (CF) Database (UKCFD). MATERIALS AND METHODS: All active patients for 2002 from the UKCFD were analysed in 1-year cohorts from 0 to 18 years. Northern Score results from the annual review forms were used to construct centile lines for the 5th, 25th, 50th, 75th, 95th centiles. RESULTS: There were 1806 patients with recorded Northern Score data for 2002 (927 male patients, male:female ratio 1.05). The centile chart demonstrates a quasi-linear rise throughout childhood. A Northern Score in excess of age in years equates to >95th centile in school-aged CF patients. CONCLUSION: This centile chart provides a disease-specific reference range for monitoring individual patients or for evaluating therapeutic change using the dominant chest radiograph scoring system in the UK. Patients, parents and clinicians may find these useful during the annual review process.

Aging↗
PubMed2005

Cardioprotection mediated by urocortin is dependent on PKCepsilon activation.

Urocortin (Ucn) is an endogenous cardioprotective agent that protects against the damaging effects of ischemia and reperfusion injury in vitro and in vivo. We have found that the mechanism of action of Ucn involves both acute activation of specific target molecules, and using Affymetrix (Santa Clara, CA) gene chip technology, altered gene expression of different end effector molecules. Here, from our gene chip data, we show that after a 24 h exposure to Ucn, there was a specific increase in mRNA and protein levels of the protein kinase C epsilon (PKCepsilon) isozyme in primary rat cardiomyocytes compared with untreated cells and in the Langendorff perfused ex vivo heart. Furthermore, a short 10 min exposure of these cells to Ucn caused a specific translocation/activation of PKCepsilon in vitro and in the Langendorff perfused ex vivo heart. The importance of the PKCepsilon isozyme in cardioprotection and its relationship to cardioprotection produced by Ucn was assessed using PKCepsilon-specific inhibitor peptides. The inhibitor peptide, when introduced into cardiomyocytes, caused an increase in apoptotic cell death compared with control peptide after ischemia and reperfusion. When the inhibitor peptide was present with Ucn, the cardioprotective effect of Ucn was lost. This loss of cardioprotection by Ucn was also seen in whole hearts from PKCepsilon knockout mice. These findings indicate that the cardioprotective effect of Ucn is dependent upon PKCepsilon.

Animals↗
PubMed2003

Mild cognitive impairment in the oldest old.

BACKGROUND: No data exist on whether the syndrome of amnestic mild cognitive impairment occurs in the oldest old, or if the relationships for functional status and neuropsychometric performance based on clinical diagnosis hold true in this age group. DESIGN/METHODS: The authors performed comprehensive neurologic evaluations, neuropsychometric testing, and functional assessments on a sample of 90- to 100-year-old residents of Rochester, MN. Subjects were diagnosed as normal or with amnestic mild cognitive impairment (MCI) or dementia according to well-accepted criteria. Data on the following measures were collected and analyzed: Record of Independent Living (ROIL), Mini-Mental State Examination (MMSE), Dementia Rating Scale (DRS), Trailmaking Test (TMT), and modified version of the Free and Cued Selective Reminding Test (FCSRT). RESULTS: Data on 111 subjects (56 normal, 13 MCI, and 42 dementia) were analyzed. On the ROIL, functional capacity to carry out activities of daily living was worse for patients with dementia compared to patients with MCI and normal subjects, but did not differ between MCI and normal subjects. Scores on the MMSE, DRS, and TMT-A were worse in the dementia group compared to the normal group, and in the dementia group compared to MCI, but scores on these measures for normal subjects compared to patients with MCI were not different. Scores on the FCSRT and memory subtest of the DRS showed differences among all three groups. CONCLUSION: In spite of the advanced age of the cohort, the relationship between cognitive and functional performance and clinical diagnosis follows patterns previously described in younger samples of normal subjects, subjects with amnestic mild cognitive impairment, and subjects with dementia.

Age Distribution↗
PubMed2002

Binding affinities and geometries of various metal ligands in peptide deformylase inhibitors.

Removal of the N-terminal formyl group from newly synthesized proteins by the enzyme peptide deformylase (PDF) is essential for normal growth of bacteria but not higher organisms. Recently, PDF has been explored as a target for novel antibiotics. Screening a collection of natural products for antimicrobial activity identified actinonin and two matlystatin analogs as potent PDF inhibitors. A number of synthetic analogs of these natural products were prepared and their inhibitory potency determined. Previous work has shown that PDF is an iron metalloproteinase also containing a catalytic glutamic acid residue. Ligation of the ferrous cation is an essential feature of potent inhibitors. The structures of actinonin, a matlystatin analog and a synthetic inhibitor complexed with PDF were determined by crystallography. A quantum mechanics/molecular mechanics (QM/MM) method was used to reproduce the geometry of known complexes, to predict the protonation state in the active site and to predict the geometry of additional complexes. The requirement for protonation of the active site glutamate anion is an important factor in understanding the potency of inhibitors with acidic iron-ligating groups such as hydroxamate and carboxylate. Even though potent inhibitors of PDF have been discovered, their bacteriostatic mechanism of action and the rapid development of resistance in vitro may limit their potential as antibacterial drugs.

Amidohydrolases↗
PubMed2001

Nursing the ARDS patient in the prone position: the experience of qualified ICU nurses.

The revival of the use of the prone position as a treatment for acute respiratory distress syndrome (ARDS) has been well documented in the medical literature, but there is little information regarding the difficulties of nursing patients in this position. The purpose of this study was to increase the body of knowledge by exploring the experiences of nurses who had cared for a patient in the prone position. A questionnaire was sent to all registered nurses in four large intensive care units (ICUs) to determine the main areas of concern when nursing patients in the prone position. There was a 62% response rate. Following this, a sample of 12 nurses volunteered to participate in three focus group interviews to further explore the issues. The main difficulties experienced related to the manoeuvre, including the timing of the move, the number of personnel and the co-ordination required. Problems experienced in providing nursing care related to pressure areas, suctioning, accidental injuries and management of emergencies. Deficits in knowledge of ARDS and skills in handling communication with relatives were also identified. As a result of this exploration, guidelines have been developed, focusing mainly on the manoeuvre, organizational and nursing issues, to provide guidance in caring for a patient when being nursed in the prone position.

Humans↗
PubMed2000

Insulin receptor substrate-1, p70S6K, and cell size in transformation and differentiation of hemopoietic cells.

After an initial burst of cell proliferation, the type 1 insulin-like growth factor receptor (IGF-IR) induces granulocytic differentiation of 32D IGF-IR cells, an interleukin-3-dependent murine hemopoietic cell line devoid of insulin receptor substrate-1 (IRS-1). The combined expression of the IGF-IR and IRS-1 (32D IGF-IR/IRS-1 cells) inhibits IGF-I-mediated differentiation, and causes malignant transformation of 32D cells. Because of the role of IRS-1 in changing the fate of 32D IGF-IR cells from differentiation (and subsequent cell death) to malignant transformation, we have looked for differences in IGF-IR signaling between 32D IGF-IR and 32D IGF-IR/IRS-1 cells. In this report, we have focused on p70(S6K), which is activated by the IRS-1 pathway. We find that the ectopic expression of IRS-1 and the inhibition of differentiation correlated with a sustained activation of p70(S6K) and an increase in cell size. Phosphorylation in vivo of threonine 389 and, to a lesser extent, of threonine 421/serine 424 of p70(S6K) seemed to be a requirement for inhibition of differentiation. A role of IRS-1 and p70(S6K) in the alternative between transformation or differentiation of 32D IGF-IR cells was confirmed by findings that inhibition of p70(S6K) activation or IRS-1 signaling, by rapamycin or okadaic acid, induced differentiation of 32D IGF-IR/IRS-1 cells. We have also found that the expression of myeloperoxidase mRNA (a marker of differentiation, which sharply increases in 32D IGF-IR cells), does not increase in 32D IGF-IR/IRS-1 cells, suggesting that the expression of IRS-1 in 32D IGF-IR cells causes the extinction of the differentiation program initiated by the IGF-IR, while leaving intact its proliferation program.

Animals↗
PubMed2000

Patient preferences regarding pain medication in the ED.

Previous studies have reported inadequate pain control in the emergency department (ED). The primary purpose of this study was to determine the proportion of ED patients with acute fractures who actually wanted pain medication given in the ED. A convenience sample of 107 adults with acute long-bone fractures seen in a community hospital ED were surveyed on the pain level they had on ED presentation, the pain level desired at ED discharge, and their preferences for administration of analgesia in the ED. Eighty-eight percent of the patients wanted pain medication given in the ED and 77% actually received it. Sixty-nine percent were comfortable with a nurse administering pain medication before physician evaluation. Seventy percent wanted pain control without being sedated and 25% wanted complete pain relief even if sedation was necessary to achieve it. Sixty percent were either slightly concerned or not concerned about potential medication side effects.

Adult↗
PubMed2000

Prostacyclin-induced relaxations of small porcine pulmonary arteries are enhanced by the basal release of endothelium-derived nitric oxide through an effect on cyclic GMP-inhibited-cyclic AMP phosphodiesterase.

AIM: To study the interactions between prostacyclin and endothelium-derived nitric oxide in porcine pulmonary arteries. METHODS: Rings of 5th order of porcine pulmonary arteries were studied in vitro for the measurement of tension and the content in cyclic nucleotides. RESULTS: Prostacyclin, given exogenously, caused endothelium-potentiated relaxations (inhibition of phenylephrine contraction) that were inhibited by the inhibitors of the L-arginine nitric oxide pathway, oxyhemoglobin and N omega-nitro-L-arginine. These inhibitors did not affect the tension in rings without endothelium. Cyclic GMP-concentrations were not increased above basal concentrations in the presence of prostacyclin. Increases were seen with acetylcholine and sodium nitroprusside. Prostacyclin-stimulated cyclic AMP concentrations did not reach statistical significance compared to controls. The addition of 8-bromo-cyclic GMP to prostacyclin, however, increased the cyclic AMP content. The nitric oxide synthase inhibitor, nitro-L-arginine (NLA), reduced the prostacyclin-stimulated cyclic AMP content to basal level. Inhibition of cyclic GMP-inhibited cyclic AMP phosphodiesterase by 8-bromo-cyclic GMP or amrinone (a specific inhibitor of this enzyme) potentiated the prostacyclin-induced relaxations in rings without endothelium to a magnitude similar to that observed in rings with endothelium. CONCLUSION: These data suggest that the augmentation by the endothelium of the prostacyclin-induced relaxation of porcine pulmonary arteries is secondary to the inhibition of cyclic GMP-inhibited cyclic AMP phosphodiesterase by basally released endothelium-derived nitric oxide.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1999

Regulation of Drosophila FMRFamide neuropeptide gene expression.

Physiologically important peptides are often encoded in precursors that contain several gene products; thus, regulation of expression of polypeptide proteins is crucial to transduction pathways. Differential processing of precursors by cell- or tissue-specific proteolytic enzymes can yield messengers with diverse distributions and dissimilar activities. FMRFamide-related peptides (FaRPs) are present throughout the animal kingdom and affect both neural and gastrointestinal functions. Organisms have several genes encoding numerous FaRPs with a common C-terminal structure but different N-terminal amino acid extensions. We have isolated SDNFMRFamide, DPKQDFMRFamide, and TPAEDFMRFamide contained in the Drosophila FMRFamide gene. To investigate the regulation of expression of FMRFamide peptides, we generated antisera to distinguish among the three neuropeptides. We have previously reported the distribution of SDNFMRFamide and DPKQDFMRFamide. In this article, we describe TPAEDFMRFamide expression. TPAEDFMRFamide antisera stain cells in embryonic, larval, pupal, and adult thoracic and abdominal ganglia. In addition, TPAEDFMRFamide-immunoreactive material is present in a lateral protocerebrum cell in adult. Thus, TPAEDFMRFamide antisera staining of neural tissue is different from SDNFMRFamide or DPKQDFMRFamide. In addition, TPAEDFMRFamide antisera stain larval, pupal, and adult gut, while SDNFMRFamide and DPKQDFMRFamide do not. TPAEDFMRFamide immunoreactivity is present in cells stained by FMRFamide antisera. Taken together, these data support the conclusion that TPAEDFMRFamide is differentially processed from the FMRFamide polypeptide protein precursor and may act in both neural and gastrointestinal tissue.

Animals↗
PubMed1999

Neuropeptide precursor processing detected by triple immunolabeling.

Peptides that play critical physiological roles are often encoded in precursors that contain several gene products. Differential processing of a polypeptide precursor by cell-specific proteolytic enzymes can yield multiple messengers with diverse distributions and functions. We have isolated SDNFMRFamide, DPKQDFMRFamide, and TPAEDFMRFamide from Drosophila melanogaster. The peptides are encoded in the FMRFamide gene and have a common C-terminal FMRFamide but different N-terminal extensions. In order to investigate the regulation of expression of FMRFamide peptides, we generated antisera to distinguish between the structurally related neuropeptides. We established a triple-label immunofluorescence protocol using antisera raised in the same host species and mapped the neural distribution of SDNFMRFamide, DPKQDFMRFamide, and TPAEDFMRFamide. Each peptide has a unique, nonoverlapping cellular expression pattern, suggesting that the precursor is differentially processed. Thus, our data indicate that D. melanogaster contains cell-specific proteolytic enzymes to cleave a polypeptide protein precursor, resulting in unique expression patterns of neuropeptides.

Animals↗
PubMed1999

Blunt trauma-induced bilateral chylothorax.

This report describes the case of a man who presented in a delayed manner after blunt trauma with bilateral chylothoraces, a rare result of trauma. He presented with shortness of breath and chest pain. A diagnostic workup resulted in the determination of traumatic chylothorax. His course in the hospital identified a disruption at a level of the 5th thoracic vertebra. No surgical ligation was required because his leak spontaneously sealed after conservative measures. The anatomy, physiology, mechanisms, and management of this injury are discussed.

Chest Pain↗
PubMed1999

Involvement of intermediary metabolites in the pathway of extracellular Ca2+-induced mitogen-activated protein kinase activation in human fibroblasts.

Human fibroblasts in culture will grow in serum-free medium containing serum replacement factors, but without protein growth factors, as long as the Ca2+ level is 1.0-2.0 mM. When the Ca2+ is reduced to 0.1 mM, the cells stop cycling, but they can be reinduced to cycle by raising the Ca2+ level to 1.0 mM Ca2+ or to higher concentrations that result in activation of mitogen-activated protein kinase (MAPK). We now report that exposure of human fibroblasts to extracellular Ca2+ increased the level of inositol (1,4,5)-trisphosphate in the cytoplasm and caused a transient rise in the concentration of intracellular free Ca2+. Ca2+-induced MAPK activation was partly abolished by treatment of the cells with pertussis toxin. It was also decreased by treatment of cells with thapsigargin, which depletes intracellular Ca2+ stores; with phorbol 12-myristyl 13-acetate (PMA), which down-regulates protein kinase C (PKC); with the calmodulin antagonists N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide HCl (W-7), and calmidazolium (24571); as well as with lanthanum, a Ca2+ channel inhibitor. Ca2+ stimulation did not result in phosphorylation of the c-raf-1 protein. Our results suggest that extracellular Ca2+ stimulates MAPK activation through a pathway(s) involving a pertussis toxin-sensitive G protein, phospholipase C, intracellular free Ca2+, calmodulin, and PKC.

Animals↗
PubMed1999

Antisera to multiple antigenic peptides detect neuropeptide processing.

Peptides act as critical messengers of essential physiological function. Frequently, several peptides are encoded in the same precursor and, often, there is structure relatedness among the gene products. The complexity of protein precursors and presence of homologous peptides raises issues about regulation of gene expression and function of structurally-related peptides. We have determined the cellular location of DPKQDFMRFamide and SDNFMRFamide encoded in the Drosophila FMRFamide gene. We raised antisera that distinguish between the two peptides and conducted double label immunostaining utilizing antisera raised in the same host species. We found that DPKQDFMRFamide and SDNFMRFamide are present in distinct distribution patterns. We also established that the peptides are present in cells stained by FMRFamide antisera. Thus, our data are consistent with the conclusion that Drosophila contains cell-specific proteolytic processing enzymes capable of posttranslationally cleaving a polypeptide protein precursor to yield unique expression patterns of neuropeptides that may have diverse activities.

Animals↗
PubMed1999

Cost of chickenpox in Canada: part II. Cost of complicated cases and total economic impact. The Immunization Monitoring Program-Active (IMPACT).

OBJECTIVE: Primarily, to determine the direct medical costs and productivity losses associated with complicated chickenpox (hospitalized cases) and, secondarily, to quantify the overall economic burden of chickenpox in Canada. METHODS: Direct medical resource consumption patterns were determined by chart review of 160 otherwise healthy children and 40 children with leukemia hospitalized for chickenpox. Children were selected from the database of the Immunization Monitoring Program Active (IMPACT), a network of 11 tertiary-care hospitals in Canada that collected information at the time of hospitalization from January 1991 to March 1996. An additional 26 healthy children hospitalized were recruited prospectively by IMPACT. Productivity losses (time lost from work and daily activities) were assessed by caregiver interviews. Treatment costs were determined from the patient, Ministry of Health, and societal perspectives. RESULTS: The average societal per case cost for complicated chickenpox in healthy children was $7060 and $8398, respectively, from the retrospective and prospective assessments. For children with leukemia, the direct medical cost was estimated at $7228. These costs were combined with a cost established previously for uncomplicated chickenpox. The estimated yearly overall economic impact of chickenpox in Canada was $122.4 million, with $24.0 million attributable to Ministry of Health costs, assuming an estimated yearly incidence of 346 527 cases and a 0.54% rate of hospitalization for healthy children. CONCLUSIONS: Direct medical costs are the major cost driver in the care of complicated chickenpox. However, in the context of the overall economic burden of the disease, uncomplicated chickenpox is the major cost driver, contributing 89% to the total cost.

Canada↗