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Biomedical subjects

E McKenzie

Publications and source records attributed to E McKenzie.

17 recordsLinked to original sources
PubMed2002

Functional magnetic resonance imaging of tonic pain and vasopressor effects in rats.

In functional magnetic resonance imaging (fMRI) studies, an elevation in blood pressure (BP) in individuals with a poor autoregulatory response may increase cerebral blood flow, potentially enhancing the blood oxygenation level dependent response. To investigate the role of BP changes, the cerebral activation to either tonic pain or the infusion of the vasopressor norepinephrine was correlated with the accompanying BP changes in alpha-chloralose anesthetized rats. Immediately after formalin (2%) injection into the forepaw, fMRI detected an activation that was correlated with the BP increase and additional activations that were independent of blood pressure changes 5-40 minutes later. The activation detected with the administration of the vasopressor norepinephrine, which does not cross the blood-brain barrier was correlated to both the amount and rate of increase in BP. The response ranged from being sparse, localized within cortex or widespread during modest, moderate or severe elevations in BP, respectively. The cerebral circulatory effects of hypertension should be considered as contributing to changes in cerebral blood oxygenation in fMRI studies involving increases in BP.

Analgesics, Opioid↗
PubMed2000

Cloning and expression profiling of Hpa2, a novel mammalian heparanase family member.

Heparan sulfate proteoglycans are important constituents of the extracellular matrix and basement membrane. Cleavage of heparan sulfate by heparanase, an endoglycosidase, is implicated in the extravasation of leukocytes and metastatic tumour cells, identifying this enzyme(s) as a target for anti-inflammatory and anti-metastatic therapies. The cloning of a cDNA encoding human heparanase (Hpa1) was reported recently, together with evidence indicating that the hpa1 gene is unique and unlikely to belong to a family of related genes. Here we report the cloning of a cDNA encoding a novel human protein, HPA2, with significant homology to Hpa1. Alternative splicing of the hpa2 transcript yields three different mRNAs, encoding putative proteins of 480, 534, and 592 amino acids. Sequence analyses predict that all three Hpa2 proteins are intracellular, membrane-bound enzymes. Hpa2 also shows a markedly different mRNA distribution to Hpa1 in both normal and cancer tissues. The difference in expression profiles and predicted cellular locations suggests that Hpa2 and Hpa1 proteins have distinct biological functions.

Alternative Splicing↗
PubMed1998

Rac-1 regulates nuclear factor of activated T cells (NFAT) C1 nuclear translocation in response to Fcepsilon receptor type 1 stimulation of mast cells.

Transcription factors of the nuclear factor of activated T cells (NFAT) family play a key role in antigen receptor-mediated responses in lymphocytes by controlling induction of a wide variety of cytokine genes. The GTPases Ras and Rac-1 have essential functions in regulation of NFAT transcriptional activity in the mast cell system, where Fcepsilon receptor type 1 (FcepsilonR1) ligation results in induction of multiple NFAT target genes. This report examines the precise biochemical basis for the Rac-1 dependency of FcepsilonR1 activation of NFAT in mast cells. We are able to place Rac-1 in two positions in the signaling network that regulates the assembly and activation of NFAT transcriptional complexes in lymphocytes. First, we show that activity of Rac-1 is required for FcepsilonR1-mediated NFATC1 dephosphorylation and nuclear import. Regulation of NFAT localization by the FcepsilonR1 is a Rac-dependent but Ras-independent process. This novel signaling role for Rac-1 is distinct from its established regulation of the actin cytoskeleton. Our data also reveal a second GTPase signaling pathway regulating NFAT transcriptional activity, in which Rac-1 mediates a Ras signal. These data illustrate that the GTPase Rac-1 should now be considered as a component of the therapeutically important pathways controlling NFATC1 subcellular localization. They also reveal that GTPases may serve multiple functions in cellular responses to antigen receptor ligation.

Actins↗
PubMed1992

Danazol in the treatment of menorrhagia: the effect of a 1 month induction dose (200 mg) and 2 month's maintenance therapy (200 mg, 100 mg, 50 mg or placebo).

This paper highlights the difficulties of recruiting subjects to objective menstrual blood loss (MBL) studies. Such difficulties may explain the relative paucity of such studies in the literature. Eleven women with objectively assessed evidence of menorrhagia were treated for 1 month with an induction dose of 200 mg of danazol (Danocrine). Subsequently the women were randomly assigned to receive 50, 100 or 200 mg of danazol or placebo for 2 months of maintenance dosing. Follow-up with objective assessment of MBL was continued for 3 months after cessation of maintenance dosing. Danazol 200 mg as an induction dose significantly reduced MBL. The maintenance dose of 200 mg during the following 2 months produced a further decrease in MBL and in some cases amenorrhoea. The lower maintenance dosages of 50 mg and 100 mg were associated with a variable response. The study was unable to determine whether any beneficial effect of the maintenance dosages of danazol could be maintained following cessation of therapy since the study numbers had become too small. It appears, however, that there is unlikely to be any persisting benefit once therapy has ceased.

Adult↗
PubMed1989

Does the abnormal pattern of breathing in patients with interstitial lung disease persist in deep, non-rapid eye movement sleep?

Patients with interstitial lung disease (ILD) characteristically exhibit an increased ventilation and breathing frequency when awake. We wanted to see if these increases persisted during deep non-REM sleep. Using noninvasive techniques, we have quantified the pattern of breathing, arterial oxygen saturation, and transcutaneous PCO2 (PtcCO2) during standardized conditions of relaxed wakefulness and during Stage 4 (S4) sleep in eight patients with ILD and eight age-matched normal control subjects. The patients were given supplemental oxygen in order to prevent hypoxic ventilatory stimulation. The data were compared between the two groups during each of these states and also between states within each group. During wakefulness in the patients, respiratory frequency (f) and PtcCO2 were higher (p less than 0.001 and p less than 0.05, respectively) and inspiratory time (TI) and expiratory time (TE) were shorter (p less than 0.05 and p less than 0.001, respectively) than in the normal subjects. However, during S4 sleep, there were no significant differences between groups. Comparing wakefulness with S4 sleep: in the normal subjects during sleep, f and PtcCO2 were increased (p less than 0.01 and p less than 0.05, respectively), TE was shortened (p less than 0.01), and ventilation (VI) was unchanged. In contrast, in the patients, f decreased (p less than 0.001), TE lengthened (p less than 0.01), VI decreased (p less than 0.05), and the rise in PtcCO2 seen in the normal subjects during sleep did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

The effect of human heart-lung transplantation upon breathing at rest and during sleep.

We have assessed the contribution of intrathoracic pulmonary nerves to the control of breathing in humans. During relaxed wakefulness and during sleep the level, pattern and variability of breathing have been quantified in 8 healthy patients 1 month to 2 years after combined heart--lung transplantation. These data have been compared with similar data from both of 2 matched control groups; either healthy normal controls, or healthy patients after heart transplantation alone. We found no significant differences in the mean levels of respiratory variables between the 3 groups either during relaxed wakefulness or sleep. There were no significant differences between groups (other than would be expected by chance alone) either in the variability of breathing, or in the shapes of the frequency distributions of respiratory variables during these states. There were no respiratory disorders associated with sleep nor any disturbances in blood gases in any group. We conclude that in man breathing is remarkably normal, during relaxed wakefulness and during sleep, after chronic pulmonary denervation. When the ventilatory demands are minimal the human ventilation system functions normally in the absence of a control loop involving pulmonary proprioceptors and the medullary respiratory centres.

Adolescent↗
PubMed1985

Cloning and sequence analysis of an Ig lambda light chain mRNA expressed in the Burkitt's lymphoma cell line EB4.

A cDNA library was constructed from the mRNA of the Ig lambda producing Burkitt's lymphoma cell line, EB4. Overlapping clones encompassing the coding sequence of the Ig lambda mRNA were isolated and sequenced. The predicted amino acid sequence shows a short hydrophobic leader peptide and a mature polypeptide of 217 residues in which V, J and C regions can be distinguished. The V region belongs to subgroup VI and has greatest homology (80%) with the Amyloid-AR protein. The constant region is the Kern- Oz+ isotype. Probing normal human DNA with the subcloned V lambda coding sequence detects one gene at high stringency and a family of 11 members at low stringency. To date, no restriction enzyme site polymorphisms have been detected. The V lambda VI gene is rearranged on both chromosomes of EB4 and is deleted on both chromosomes in the Burkitt's lymphoma cell line BL2.

Base Sequence↗
PubMed1985

Maturation of the brain-stem auditory evoked potential in premature infants.

Patterns of development and extent of variability of the brain-stem auditory evoked potential (BAEP) are described in 52 healthy premature infants and 50 normal term newborns with reliable conceptional ages. Binaural and monaural stimulation are compared. Serial studies of individual prematures are emphasized and demonstrate that the most consistent and least variable measures are the monaurally derived interpeak intervals. All the BAEP parameters studied mature including wave form, relative amplitude, peak and interpeak intervals, but there is far more variability in preterms than in term infants or adults, even when infants are carefully matched for conceptional age. As term is approached, BAEP variability decreases substantially, suggesting that near term the BAEP becomes a more reliable indicator of neurologic function. The variability of the BAEP in the normal preterm limits its usefulness in determining neurologic dysfunction in individual high risk infants. Nevertheless, the BAEP may still prove useful for defining group differences among infants and could provide an objective measure of those factors influencing neurologic development. Serial change in the BAEP is a specific parameter which we believe merits further study in premature infants as an index of neurologic maturation.

Brain Stem↗
PubMed1984

Ultrasound imaging in the management of ovulation stimulation.

The present role of ultrasound imaging in the assessment of ovarian response to gonadotrophin therapy was assessed by comparing a group of patients in whom ultrasound was used to determine suitability of follicles for induction of ovulation with a group in whom ultrasound was not available. Ultrasound provides new and useful information, and may allow a reduction in the incidence of multiple pregnancies.

Adult↗
PubMed1982

A study of the recommended pass/fail criteria for impedance audiometry in a school screening program.

One hundred and nine children enrolled in kindergarten to grade 3 were studied audiologically and otologically over a three month period to examine pass/fail criteria that have been recommended for impedance audiometry in school screening programs. Results indicated that tympanogram type (flat or rounded) and puretones of 2,000 Hz (20 dB) and 4,000 Hz (25 dB) agreed most often with the ENT diagnosis of significant middle ear pathology. These pass/fail criteria also gave a reasonably acceptable over and under referral rate. A third screening is recommended one month following the first and second screenings, and if the child continues to "fail" a medical referral is suggested. There are at least two limitations of current automated impedance screening devices--pressure range, and acoustic reflex sensitivity, which will produce unnecessary failures due solely to instrumentation.

Acoustic Impedance Tests↗
PubMed1976

Mobile hearing program in central rural Manitoba.

A mobile hearing program was developed to detect and alleviate deafness and rehabilitate deaf individuals in rural Manitoba. The first project was established in central Manitoba in December 1973 for children, whose school performance can be affected by minimal hearing loss. Volunteers from the community, trained by an audiologist, conduct screening procedures, and children with possible hearing impairment receive audiologic and otolaryngologic assessment. Close clinical liaison between audiologist and otologist is important.

Child↗
PubMedDate not supplied

Inter-provincial variation in government drug formularies.

In Canada, coverage for ambulatory prescription drug expenditures is provided to some groups by provincial drug plans through a provincial formulary. Little is known about the drugs provincial formularies give access to. We report the variation in availability of new drug molecules (NDM) across provincial formularies. We identified 108 NDM approved in Canada between 1991 and 1998. From each drug plan bulletin or formulary, we abstracted names of NDM listed as per 15 January 1999. We compared the level of listing across provinces using kappa coefficients. In the Quebec, BC, Manitoba and Saskatchewan formularies, more than 70% of the NDM were listed. In four provinces, this proportion was lower than 50%. In general, the agreement between formularies was poor. There is a wide variation across provinces in terms of NDM listed in the formularies. This variation reflects inter-provincial differences in the way drugs are selected for coverage.

Canada↗