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Biomedical subjects

P Wade

Publications and source records attributed to P Wade.

At least 19 recordsLinked to original sources
PubMed2006

Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug.

Although dysregulation of tight junction (TJ) proteins is observed in epithelial malignancy, their participation in epithelial transformation is poorly understood. Recently we demonstrated that expression of oncogenic Raf 1 in Pa4 epithelial cells disrupts TJs and induces an oncogenic phenotype by downregulating expression of the TJ protein, occludin. Here we report the mechanism by which Raf 1 regulates occludin expression. Raf 1 inhibited occludin transcription by repressing a minimal segment of the occludin promoter in concert with upregulation of the transcriptional repressor, Slug without influencing the well-documented transcriptional repressor, Snail. Overexpression of Slug in Pa4 cells recapitulated the effect of Raf 1 on occludin expression, and depletion of Slug by small interfering RNA abrogated the effect of Raf 1 on occludin. Finally, chromatin immunoprecipitation assays and site-directed mutagenesis demonstrated a direct interaction between Slug and an E-box within the minimal Raf 1-responsive segment of the occludin promoter. These findings support a role of Slug in mediating Raf 1-induced transcriptional repression of occludin and subsequent epithelial to mesenchymal transition.

Animals↗
PubMed2002

Phylogeographical approaches to assessing demographic connectivity between breeding and overwintering regions in a Nearctic-Neotropical warbler (Wilsonia pusilla).

We characterized the pattern and magnitude of phylogeographical variation among breeding populations of a long-distance migratory bird, the Wilson's warbler (Wilsonia pusilla), and used this information to assess the utility of mtDNA markers for assaying demographic connectivity between breeding and overwintering regions. We found a complex pattern of population differentiation in mitochondrial DNA (mtDNA) variation among populations across the breeding range. Individuals from eastern North America were differentiated from western individuals and the eastern haplotypes formed a distinct, well-supported cluster. The more diverse western group contained haplotype clusters with significant geographical structuring, but there was also broad mixing of haplotype groups such that no haplotype groups were population specific and the predominance of rare haplotypes limited the utility of frequency-based assignment techniques. Nonetheless, the existence of geographically diagnosable eastern vs. western haplotypes enabled us to characterize the distribution of these two groups across 14 overwintering locations. Western haplotypes were present at much higher frequencies than eastern haplotypes at most overwintering sites. Application of this mtDNA-based method of linking breeding and overwintering populations on a finer geographical scale was precluded by the absence of population-specific markers and by insufficient haplotype sorting among western breeding populations. Our results suggest that because migratory species such as the Wilson's warbler likely experienced extensive gene flow among regional breeding populations, molecular markers will have the greatest utility for characterizing breeding-overwintering connectivity at a broad geographical scale.

Animal Migration↗
PubMed2001

Systemic antibiotics fail to clear multidrug-resistant Klebsiella from a pediatric ICU.

STUDY OBJECTIVES: To determine the magnitude of infection rate and antimicrobial resistance in a pediatric ICU (PICU), and to evaluate the efficacy of using broad-spectrum antibiotics. DESIGN: A 3-month, prospective, observational cohort audit. SETTING: A 12-bed tertiary, referral PICU. PATIENTS OR PARTICIPANTS: All children admitted to the PICU for > 72 h. INTERVENTIONS: Surveillance cultures of throat and rectum on admission and once weekly thereafter. MEASUREMENTS AND RESULTS: Of the 150 admissions during the 3-month period, a total of 52 patients (24 girls and 28 boys) requiring mechanical ventilation for a minimum of 3 days were enrolled in the audit. The median age and interquartile range (IQR) was 17 months (IQR, 5.8 to 63); length of stay, 6.5 days (IQR, 4 to 13); ventilation days, 5 (IQR, 3 to 11); pediatric risk of mortality score, 14 (IQR, 9 to 19); and risk of mortality, 0.03 (IQR, 0.014 to 0.087). Fifteen patients (29%) developed 21 infections, mainly lower-airway infections and septicemias. Of the 52 children, 7 children carried multidrug-resistant bacteria and 3 patients progressed to develop four infections with those resistant bacteria. Of the seven carriers, six patients carried gentamicin-resistant Klebsiella. Methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae and gentamicin-resistant Pseudomonas aeruginosa each were carried by one child. Six of those nine resistant isolates were present in the admission flora. Despite the potent combination of piperacillin/tazobactam and amikacin, three children acquired the multidrug-resistant Klebsiella while in the PICU and became nosocomial carriers. CONCLUSIONS: Only surveillance cultures allow the distinction between import of multidrug-resistance and resistant bacteria acquired while in PICU. In this study, two thirds of the resistant isolates were imported. The introduction of newer potent systemic antibiotic combinations failed to control the endemic reservoir of multidrug-resistant Klebsiella and suggests that such policies have little impact.

Amikacin↗
PubMed2001

An ethical dilemma.

Explore the source record for details and available documents.

Blood Transfusion↗
PubMed2000

A case of Balamuthia mandrillaris meningoencephalitis.

Balamuthia mandrillaris is a newly described pathogen that causes granulomatous amebic encephalitis, an extremely rare clinical entity that usually occurs in immunosuppressed individuals. We report a case of pathologically proven Balamuthia encephalitis with unusual laboratory and radiologic findings. A 52-year-old woman with idiopathic seizures and a 2-year history of chronic neutropenia of unknown cause had a subacute illness with progressive lethargy, headaches, and coma and died 3 months after the onset of symptoms. Cerebrospinal fluid (CSF) glucose concentrations were extremely low or unmeasurable, a feature not previously described (to our knowledge). Cranial magnetic resonance imaging scans showed a single large temporal lobe nodule, followed 6 weeks later by the appearance of 18 ring-enhancing lesions in the cerebral hemispheres that disappeared after treatment with antibiotics and high-dose corticosteroids. The initial brain biopsy specimen and analysis of CSF samples did not demonstate amebae, but a second biopsy specimen and the postmortem pathologic examination showed Balamuthia trophozoites surrounded by widespread granulomatous inflammation and vasculitis. The patient's neutropenia and antibiotic use may have caused susceptibility to this organism. Amebic meningoencephalitis should be considered in cases of subacute meningoencephalitis with greatly depressed CSF glucose concentrations and multiple nodular lesions on cerebral imaging. Arch Neurol. 2000;57:1210-1212

Amebiasis↗
PubMed1999

Characterization of a chromatin remodelling activity in Xenopus oocytes.

The yeast SWI2/SNF2 protein is a component of a large protein complex which is involved in the remodelling of chromatin during transcriptional activation. Several homologous complexes have been found in Drosophila and mammals. We have examined the expression of the SWI2/SNF2 homologue BRG1 in Xenopus laevis using two antisera originally raised against the C-terminus of the rat and the human BRG1 protein. These two antisera cross-reacted with a protein found in both Xenopus liver and Xenopus oocytes. The Xenopus BRG1-like protein is expressed throughout oogenesis (stages I-VI) and embryogenesis. By injecting an expression vector containing the full-length human BRG1 cDNA into Xenopus oocytes, the relative molecular weight (Mr) of the Xenopus BRG1-like protein was shown to be slightly lower than that of the human BRG1, 190 000 and 200 000, respectively. The Xenopus BRG1-like protein elutes at a Mr of approximately 2 000 000 on Superose HR6trade mark size-exclusion chromatography, indicating that it is part of a larger complex, as are all other known SWI/SNF proteins. Nucleosome remodelling activity was co-eluted with the BRG1 immunogenic activity in both ion-exchange and size-exclusion chromatography.

Animals↗
PubMed1998

Kinetics and toxicity of liposomal and conventional amikacin in a patient with multidrug-resistant tuberculosis.

The pharmacokinetics and toxicity of liposomal amikacin in a patient treated for advanced pulmonary multidrug-resistant tuberculosis are described. A dose of 20 mg/kg of liposomal amikacin was given on alternate days for 14 days and weekly thereafter for 9 weeks, for a total dose of 20.1 g in 17 divided doses. Accumulation occurred with alternate-day, but not weekly, dosing. The serum levels of amikacin obtained with the liposomal preparation were considerably greater than those obtained with the conventional preparation (range, 81-457 mg/l vs. 4.1-37.7 mg/l). The liposomal amikacin was well tolerated and led to clinical improvement, but it failed to achieve a microbiological response. The patient's sputum remained smear- and culture-positive during the treatment period with liposomal amikacin and for 9 months afterward.

Aged↗
PubMed1998

Imaging the problem scaphoid.

Scaphoid fractures can be difficult to diagnose on X-ray, even at 2 weeks. We have compared prospectively bone scanning versus MRI scanning in 22 patients with persistent signs and symptoms suggestive of a scaphoid fracture at 2 weeks and found both methods to be sensitive, but MRI to be more specific, particularly in diagnosing soft tissue injuries like scapho-lunate ligament ruptures and triangular fibrocartilage tears. An early MRI scan at 2 weeks allows the clinician to make the appropriate decision in this group of patients whose diagnoses include; occult scaphoid fractures, other occult carpal and radial fractures, ligamentous injuries and those without apparent injuries. MRI has also been useful in defining the group of injuries which may imitate a clinically occult scaphoid fracture.

Adolescent↗
PubMed1994

Nurse practitioners, certified nurse midwives, and nurse anesthetists: changing care in acute care hospitals in New York City.

To respond to the shrinking pool of primary care physicians and to demands from managed care programs for cost containment, hospitals in New York City have increased their use of nurse practitioners, certified nurse midwives, and nurse anesthetists, creating an increased demand for these personnel. We report here on a survey of hospitals and schools of nursing in New York City and present findings on (a) current use of, and projected demand for nurse practitioners (NPs), certified nurse midwives (midwives) and nurse anesthetists (anesthetists) in hospitals in New York City; (b) the practice patterns of NPs, midwives, and anesthetists currently employed in hospitals; and (c) current and projected enrollment and curriculum in NP, midwifery, and anesthetist education programs in the New York metropolitan area.

Adult↗
PubMed1987

Promyelocyte morphology. Differentiation of acute promyelocytic leukemia from benign myeloid proliferations.

Bone marrow aspirates from patients with acute agranulocytosis or a marked left shift in myeloid maturation can mimic acute leukemia, particularly acute hypergranular promyelocytic leukemia. Bone marrow aspirates from 16 cases of apparent acute promyelocytic leukemia, 4 cases of acute agranulocytosis, and 1 case of a marked myeloid left shift were studied for the presence or absence of differentiating features. Normal or reactive promyelocytes were characterized by prominent paranuclear clear Golgi zones, whereas promyelocytes from true leukemic cases all had heavy azurophilic granules dispersed diffusely throughout the cytoplasm. Prominent Golgi zones in promyelocytes were associated only with benign myeloid conditions and were not observed in acute promyelocytic leukemia. The presence of prominent clear Golgi zones in promyelocytes is an important feature assisting in the distinction between leukemic and benign promyelocytes.

Adult↗
PubMed1983

Benzodiazepines impair smooth pursuit eye movements.

Five healthy male volunteers received single oral doses of 10 mg diazepam, 20 mg temazepam and placebo, in a double-blind, randomised fashion. Smooth pursuit eye movement velocity and serum benzodiazepine concentration were measured before and after at 0.5,1,1.5,2,3,4,6,9 and 12 h after administration of the treatments. Significant decrease in smooth pursuit eye movement velocity as compared to placebo was observed between 0.5-2 h after temazepam, and between 1-2 h after diazepam. Smooth pursuit eye movement velocity was log-linearly correlated with serum temazepam and diazepam concentration. The results demonstrate the relationship between serum benzodiazepine concentration and its effect on an objective measure of oculomotor performance.

Adult↗