Biomedical subjects

C Wall

Publications and source records attributed to C Wall.

At least 37 records · Page 2Linked to original sources

PubMed1998

Role of cellular actin in the gene expression and morphogenesis of human respiratory syncytial virus.

Cytoskeletal protein actin and nonactin cellular proteins were essential for human respiratory syncytial virus (RSV) gene expression. In vitro, specific antibodies against actin inhibited RSV transcription, whereas antibodies against other cytoskeletal proteins had little or no effect. Affinity purified cellular actin or bacterially expressed recombinant actin activated RSV transcription. However, optimal transcription required additional cellular protein(s) that appeared to function as accessory factor(s) for actin. In the absence of actin, these proteins did not activate viral transcription. Purified viral nucleocapsids contained actin, but no cytokeratin, tubulin, or vimentin. Cytochalasin D or DNasel--agents that destabilize actin polymers--had little effect on RSV transcription. RSV infection itself seemed to alter the structure of the cellular actin filaments. Treatment of infected cells with cytochalasin D produced a more severe disruption of the filaments and drastically reduced the production of infectious virus particles but still had little effect on intracellular synthesis of viral macromolecules. Thus actin seems to serve a dual role in RSV life cycle: its monomeric form as well as polymeric form activate viral transcription, while only the microfilament form may take part in viral morphogenesis and/or budding.

Actin Cytoskeleton↗

PubMed1998

Overexpression of HOX11 leads to the immortalization of embryonic precursors with both primitive and definitive hematopoietic potential.

Primitive and definitive erythropoiesis represent distinct hematopoietic programs that differ with respect to stage of development, transcriptional control, and growth regulation. Although these differences have been recognized for some time, the relationship of the two erythroid lineages to each other is not well established. We have used a model system based on the hematopoietic development of embryonic stem (ES) cells in culture to investigate the origins of the earliest hematopoietic populations. Using ES cells transduced with a retrovirus that overexpresses the HOX11 gene, we have established factor-dependent hematopoietic cell lines that represent novel stages of embryonic hematopoiesis. Analysis of three of these cell lines indicates that they differ with respect to cytokine responsiveness, cell surface markers, and developmental potential. Two of the cell lines, EBHX1 and EBHX11, display the unique capacity to generate both primitive and definitive erythroid progeny as defined by morphology and expression of betaH1 and betamajor globin. The third line, EBHX14, has definitive erythroid and myeloid potential, but is unable to generate cells of the primitive erythroid lineage. Analysis of the cytokine responsiveness of the two lines with primitive erythroid potential has indicated that exposure to leukemia inhibitory factor (LIF) results in the upregulation of betaH1 and a change in cellular morphology to that of primitive erythrocytes. These findings are the first demonstration of a clonal cell line with primitive and definitive hematopoietic potential and support the interpretation that these lineages may arise from a common precursor in embryonic life. In addition, they suggest that LIF could play a role in the regulation of primitive erythropoiesis.

Animals↗

PubMed1998

The role of gut-derived bacterial toxins and free radicals in alcohol-induced liver injury.

Previous research from this laboratory using a continuous enteral ethanol (EtOH) administration model demonstrated that Kupffer cells are pivotal in the development of EtOH-induced liver injury. When Kupffer cells were destroyed using gadolinium chloride (GdCl3) or the gut was sterilized with polymyxin B and neomycin, early inflammation due to EtOH was blocked. Anti-tumour necrosis factor (TNF)-alpha antibody markedly decreased EtOH-induced liver injury and increased TNF-mRNA. These findings led to the hypothesis that EtOH-induced liver injury involves increases in circulating endotoxin leading to activation of Kupffer cells. Pimonidazole, a nitro-imidazole marker, was used to detect hypoxia in downstream pericentral regions of the lobule. Following one large dose of EtOH or chronic enteral EtOH for 1 month, pimonidazole binding was increased significantly in pericentral regions of the liver lobule, which was diminished with GdCl3. Enteral EtOH increased free radical generation detected with electron spin resonance (ESR). These radical species had coupling constants matching alpha-hydroxyethyl radical and were shown conclusively to arise from EtOH based on a doubling of the ESR lines when 13C-EtOH was given. Alpha-hydroxyethyl radical production was also blocked by the destruction of Kupffer cells with GdCl3. It is known that females develop more severe EtOH-induced liver injury more rapidly and with less EtOH than males. Female rats on the enteral protocol exhibited more rapid injury and more widespread fatty changes over a larger portion of the liver lobule than males. Plasma endotoxin, ICAM-1, free radical adducts, infiltrating neutrophils and transcription factor NFkappaB were approximately two-fold greater in livers from females than males after 4 weeks of enteral EtOH treatment. Furthermore, oestrogen treatment increased the sensitivity of Kupffer cells to endotoxin. These data are consistent with the hypothesis that Kupffer cells participate in important gender differences in liver injury caused by ethanol.

Animals↗

PubMed1997

A common precursor for primitive erythropoiesis and definitive haematopoiesis.

The generation of blood cells, haematopoiesis, in the mouse embryo begins with the development of primitive nucleated erythroid cells in the yolk sac followed by the appearance of precursors for multiple definitive haematopoietic lineages. The later developing lineages arise from multipotential stem cells, but the relationship of primitive erythroid cells to these other haematopoietic populations is unknown. Using an in vitro embryonic stem (ES) cell differentiation system, we show that primitive erythrocytes and other haematopoietic lineages arise from a common multipotential precursor that develops within embryoid bodies generated from differentiated ES cells. In response to vascular endothelial growth factor and c-kit ligand these precursors give rise to colonies containing immature cells (blasts) expressing marker genes characteristic of haematopoietic precursors. Many blast colonies also expressed betaH1 and beta major globins but not Brachyury, a mesodermal marker. Kinetic analysis demonstrated that the blast colony-forming cells represent a transient population, preceding the establishment of the primitive erythroid and other lineage-restricted precursors. This precursor population may represent the earliest stage of embryonic haematopoietic commitment.

Animals↗

PubMed1997

Role of Kupffer cells, endotoxin and free radicals in hepatotoxicity due to prolonged alcohol consumption: studies in female and male rats.

Alcohol ingestion results in increases in the release of endotoxin from gut bacteria or membrane permeability of the gut to endotoxin, or both. Female rats are more sensitive to these changes. Elevated levels of endotoxin activate Kupffer cells to release substances such as eicosanoids, tumor necrosis factor-alpha and free radicals. Prostaglandins increase oxygen uptake and most likely are responsible for the hypermetabolic state in the liver. The increase in oxygen demand leads to hypoxia in the liver, and on reperfusion, alpha-hydroxyethyl free radicals are formed that lead to tissue damage in oxygen-poor pericentral regions of the liver lobule.

Animals↗

PubMed1997

The Canadian National Breast Screening Study: update on breast cancer mortality.

The Canadian National Breast Screening Study (CNBSS), conducted on women age 40-49, was designed to evaluate the efficacy of combined annual mammography and physical examination of the breasts in reducing breast cancer mortality in comparison to usual care (UC) controls. From January 1980 through March 1985, 25,214 women were individually randomized to the mammography/physical exam (MP) arm and 25,216 to the UC. The integrity of the randomization has been reviewed and confirmed to be unbiased. During an average, follow-up of 10.5 years from entry (range: 8.75-13 years), 82 women died from breast cancer in the MP arm and 72 in the UC, for a rate ratio of 1.14 (95% confidence interval: 0.83-1.56). All-cause mortality was almost identical comparing the two groups; the nonsignificant excess of breast cancer deaths in the MP arm was balanced by an excess of other cancer deaths in the UC arm.

Adult↗

PubMed1997

A randomized, blind comparison of remifentanil and alfentanil during anesthesia for outpatient surgery.

UNLABELLED: We compared remifentanil, an esterase-metabolized opioid, with alfentanil as part of balanced anesthesia with at least 0.8% isoflurane during outpatient surgery in a randomized, double-blind trial. One hundred two patients received remifentanil, and 99 patients received alfentanil. Patients who received remifentanil experienced significantly fewer stress responses to surgical stimuli (52.9% and 65.7%, P < 0.05); significantly fewer remifentanil patients responded to skin closure (11% and 22%, P < 0.05) than patients who received alfentanil. Significantly more patients in the alfentanil group required extra analgesia compared with the remifentanil group (P < 0.05). Time to respond to verbal command was shorter for alfentanil than remifentanil (median 7 min vs 9 min), and times to spontaneous respiration (median 5 min vs 8 min), adequate respiratory rate (median 6 min vs 9 min), and tracheal extubation (median 6 min vs 9 min) were significantly shorter for alfentanil in comparison with remifentanil (P < 0.05). Remifentanil patients, however, showed significantly better recovery of psychomotor and psychometric function between 30 and 90 min after surgery (P < 0.05). The incidences of hypotension intraoperatively and shivering postoperatively were significantly higher with remifentanil. No unexpected or serious adverse events were recorded with remifentanil; however, one patient who received alfentanil experienced severe recurrent respiratory depression after surgery. The metabolic profile of remifentanil allowed better intraoperative analgesia without compromising recovery. IMPLICATIONS: The pharmacological profile of remifentanil, a new opioid for use in anesthesia, suggests that rapid recovery will occur after its use. This study of 200 outpatients shows that the differences suggested from kinetic studies are not always borne out in clinical practice, although later recovery variables did, in fact, favor remifentanil.

Adolescent↗

PubMed1997

Yaw sensory rearrangement alters pitch vestibulo-ocular reflex responses.

Ten male subjects underwent two types of adaptation paradigm designed either to enhance or to attenuate the gain of the canal-ocular reflex (COR), before undergoing otolith-ocular reflex (OOR) testing with constant velocity, earth horizontal axis and pitch rotation. The adaptation paradigm paired a 0.2 Hz sinusoidal rotation about an earth vertical axis with a 0.2 Hz optokinetic stimulus that was deliberately mismatched in peak velocity or phase and was designed to produce short-term changes in the COR. Preadaptation and postadaptation OOR tests occurred at a constant velocity of 60 degrees/sec in the dark and produced a modulation component of the slow phase velocity with a frequency of 0.16 Hz due to otolithic stimulation by the sinusoidally changing gravity vector. Of the seven subjects who showed enhancement of the COR gain, six also showed enhancement of the OOR modulation component. Of the seven subjects who showed attenuation of the COR gain, five also showed attenuation of the OOR modulation component. The probability that these two cross-axis adaptation effects would occur by chance is less than 0.02. This suggests that visual-vestibular conditioning of the yaw axis COR also induced changes in the pitch axis OOR. We thus postulate that the central nervous system pathways that process horizontal canal yaw stimuli have elements in common with those processing otolithic stimuli about the pitch axis.

Adaptation, Psychological↗

PubMed1996

Leukemia following occupational exposure to 60-Hz electric and magnetic fields among Ontario electric utility workers.

In a nested case-control study of 1,484 cancer cases and 2,179 matched controls from a cohort of 31,543 Ontario Hydro male employees, the authors evaluated associations of cancer risk with electric field exposure and reevaluated the previously reported findings for magnetic fields. Pensioners were followed from January 1, 1970, and active workers (including those who left the corporation) from January 1, 1973, with both groups followed through December 31, 1988. Exposures to electric and magnetic fields and to potential occupational confounders were estimated through job exposure matrices. Odds ratios were elevated for hematopoietic malignancies with cumulative electric field exposure. After adjustment, the odds ratio for leukemia in the upper tertile was 4.45 (95% confidence interval (CI) 1.01-19.7). Odds ratios were also elevated for acute nonlymphoid leukemia, acute myeloid leukemia, and chronic lymphoid leukemia. For cumulative magnetic field exposure, there were similar elevations that fell with adjustment. Evaluation of the combined effect of electric and magnetic fields for leukemia showed significant elevations of risk for high exposure to both, with a dose-response relation for increasing exposure to electric fields and an inconsistent effect for magnetic fields. There was some evidence of a nonsignificant association for brain cancer and benign brain tumors with magnetic fields. For lung cancer, the odds ratio for high exposure to electric and magnetic fields was 1.84 (95% CI 0.69-4.94).

Adult↗

PubMed1996

Congenital anomalies among the offspring of fire fighters.

A case-control study has been conducted to determine the association between employment as a fire fighter and congenital heart defects among the offspring. Cases were fathers of all children born between 1979 and 1986 in Ontario, Canada, who were diagnosed with a cardiac congenital anomaly during the first year of life (n = 9340). Matched controls (n = 9340), defined as fathers whose child did not have a congenital anomaly, were randomly selected from the Ontario birth certificate file. In order to identify those fathers who had been employed as a fire fighter, the cases and controls were linked to a cohort of Metropolitan Toronto fire fighters. Eleven cases and nine controls worked as fire fighters, giving an odds ratio of 1.22 (95 percent confidence interval 0.46-3.33). This study had sufficient power to detect the level of risk reported in one previous study; however, these results do not support a hypothesis of elevated risk of cardiac congenital anomalies among the offspring of fire fighters.

Adult↗

PubMed1996

Humidification reduces coughing and breath-holding during inhalation induction with isoflurane in children.

PURPOSE: Inhalation induction using isoflurane is associated with airway irritability, coughing, breath-holding and laryngospasm. These complications are more common in children. This study was designed to determine if humidification of isoflurane in oxygen/nitrous oxide would reduce respiratory complications and hypoxic episodes at induction. METHODS: Fifty-nine unpremedicated children, aged three months to 12 yr, were enrolled in the study and randomised to receive either humidified isoflurane (n = 27, Group A), or non-humidified isoflurane (n = 32, Group B). All inductions of anaesthesia were with isoflurane 4% in 50% oxygen/nitrous oxide. Subjects were observed for the occurrence of breath-holding, coughing, laryngospasm, bronchospasm, secretions, and hiccoughs. The severity of each complication was graded on a scale of 0-3. The need to administer 100% oxygen and/or succinylcholine was also identified. RESULTS: Coughing (33% vs 53%) was more frequent in Group B (P < 0.05). Coughing severity scores (13 vs 36) and breath-holding severity scores (8 vs 19) were also greater in Group B (P < 0.05). A change in FIO2 was required more frequently in Group B (4% vs 16%). Although there was a high incidence of laryngospasm in both groups (52% vs 59%), no other differences were identified, breath-holding (26% vs 31%), secretions (30% vs 31%), hiccough (11% vs 12.5%) (P > 0.05). CONCLUSION: Humidification of inspired isoflurane reduces the frequency and severity of coughing, the severity of breath-holding, and the need to increase supplemental inspired oxygen concentration, when isoflurane is used for inhalation induction of anaesthesia in children. Humidification has no effect, however, on the frequency and severity of laryngospasm, or on the frequency of occurrence of arterial oxygen desaturation.

Anesthetics, Inhalation↗

PubMed1996

Classification of human rotation test results using parametric modeling and multivariate statistics.

The usefulness of vestibular testing is directly related to the accuracy of the test interpretations. Two factors, subjective analysis of large test data sets and failure to make appropriate age corrections, tend to reduce test accuracy. Correction of these problems can be accomplished by application of physiologically based models of vestibular function and multivariate classification techniques to the test data, thereby creating a more objective test interpretation procedure. Herein we report our results on the use of this strategy for analysis of sinusoidal harmonic acceleration (SHA) test interpretation. For each patient, models reduce the large set of SHA test variables to three key parameters: asymptotic gain, vestibulo-ocular reflex time constant, and bias. In addition, the new technique objectively adjusts these parameters for the patient's age. Finally, each patient's set of parameters are statistically classified as either normal or as unilateral peripheral deficit. Based on learning sets of 57 normals and 30 patients with a full unilateral peripheral deficit, this new technique resulted in a misclassification rate between the categories of normal and full unilateral loss of 3.4%, comparing favorably to the present method's misclassification rate between normal and abnormal of 13.8%. We also analyzed and classified a test group consisting of patients with possible partial unilateral deficits using the same classification function as the normal and full unilateral learning sets. Even though the classifier was not optimized for the partial group, results seemed favorable relative to the human interpreter. These results validate the accuracy and utility of physiological parametric models and multivariate statistical classification in SHA test interpretation.

Acceleration↗

PubMed1995

Endotoxin and fibrinogen degradation product-D have different actions on carbohydrate metabolism: role of Kupffer cells.

The effect of endotoxin-derived lipopolysaccharide (LPS) and fibrinogen degradation product D (FDPD) on oxygen consumption and glycogenolysis in the perfused rat liver was investigated. 1. Infusion of LPS (100 micrograms/ml) or FDPD (7 micrograms/ml) caused a rapid stimulation of oxygen uptake by the perfused liver of 10-12 mumol/g/h. 2. LPS also caused a transient increase in glucose and lactate release into the perfusion medium from endogenous glycogen; however, FDPD was without effect. 3. Destruction of Kupffer cells by GdCl3 pretreatment blocked the effects of LPS and FDPD on oxygen uptake and glycogenolysis. Further, LPS and FDPD had no effect on oxygen consumption by isolated hepatocytes. Therefore, it is concluded that Kupffer cells are involved in the increase of hepatic oxygen consumption and carbohydrate release caused by LPS, most likely via release of PGE2 and PGD2. Since FDPD increased oxygen but not carbohydrate release, it is concluded that it acts via stimulating the release of mediators distinct from those released following LPS infusion.

Animals↗

PubMed1995

Human eye movement response to z-axis linear acceleration: the effect of varying the phase relationships between visual and vestibular inputs.

We investigated the effect of systematically varying the phase relationship between 0.5-Hz sinusoidal z-axis optokinetic (OKN) and linear acceleration stimuli upon the resulting vertical eye movement responses of five humans. Subjects lay supine on a linear sled which accelerated them sinusoidally along their z-axis at 0.4 g peak acceleration (peak velocity 1.25 m/s). A high-contrast, striped z-axis OKN stimulus moving sinusoidally at 0.5 Hz, 70 degrees/s peak velocity was presented either concurrently or with the acceleration stimulus or alone. Subjects' vertical eye movements were recorded using scleral search coils. When stimuli were paired in the naturally occurring relationship (e.g., visual stripes moving upward paired with downward physical acceleration), the response was enhanced over the response to the visual stimulus presented alone. When the stimuli were opposed (e.g., visual stripes moving upward during upward physical acceleration, a combination that does not occur naturally), the response was not significantly different from the response to the visual stimulus presented alone. Enhancement was maximized when the velocities of the visual and motion stimuli were in their normal phase relationship, while the response took intermediate values for other phase relationships. The phase of the response depended upon the phase difference between the two inputs. We suggest that linear self-motion processing looks at agreement between the two stimuli-a sensory conflict model.

Adult↗

PubMed1995

Perilymph fistula pathophysiology.

A great deal of the controversy associated with perilymph fistula is due to the lack of a sensitive, specific way of detecting and thus diagnosing one. The existing subjective, clinical observations need to be replaced with an objective, scientific methodology having higher specificity and sensitivity for the detection of perilymph fistula. Three detection methods presently under development are presented here. One uses a miniendoscope to observe the middle ear. This procedure is less traumatic than inspection with tympanotomy. Thus it is less likely to create artifacts that can be mistaken for a fistula leakage. The "yes-no" observation decision is to be replaced with a graded quantitative measure. The second method concentrates on detected leakage from inner to middle ear. beta 2-Transferrin, a unique endogenous substance found in perilymph and cerebrospinal fluid, can be detected with one- or two-dimensional gel electrophoresis and immunoblotting. The third method is a system identification fistula test. It measures a change in a physiologic response that is caused by the presence of the fistula. Classic biophysical models of the vestibular end organs can be used to predict the dynamics of responses to systems identification stimuli.

Biomarkers↗

PubMed1995

Characterization of Mu prophage lacking the central strong gyrase binding site: localization of the block in replication.

Bacteriophage Mu contains an unusually strong DNA gyrase binding site (SGS), located near the center of its genome, that is required for efficient Mu DNA replication (M. L. Pato, Proc. Natl. Acad. Sci. USA 91:7056-7060, 1994; M. L. Pato, M. M. Howe, and N. P. Higgins, Proc. Natl. Acad. Sci. USA 87:8716-8720, 1990). Replication of wild-type Mu initiates about 10 min after induction of a lysogen, while replication in the absence of the SGS is delayed about an hour. To determine which step in the replication pathway is blocked in the absence of the SGS, we inactivated the SGS by deletion and by insertion and studied the effects of these alterations on various stages of Mu DNA replication. Following induction in the absence of a functional SGS, early transcription and synthesis of the Mu-encoded replication proteins occurred normally. However, neither strand transfer nor cleavage at the Mu genome termini could be detected 40 min after induction. The data are most consistent with a requirement for the SGS in the efficient synapsis of the Mu prophage termini to form a separate chromosomal domain.

Bacteriophage mu↗

PubMed1995

Vestibular function test anomalies in patients with chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is distinguished by the new onset of debilitating fatigue that lasts at least 6 months, concomitant with other symptoms to be described later. Many CFS patients complain of disequilibrium, yet the exact type of the balance dysfunction and its function and its location (peripheral vs. central) have not been described. Herein we report results of vestibular function testing performed on 11 CFS patients. These results revealed no predominant pattern of abnormalities. Patients typically performed below average in dynamic posturography testing, with a significant number of falls in the tests requiring subjects to depend heavily on the vestibular system. One patient had abnormal caloric testing, while 3 had abnormally low earth vertical axis rotation (EVA) gains at the higher frequencies tested. As a group, the average gain of EVA was significantly lower than normals in the 0.1 - 1.0 Hz range (p < 0.05). In earth horizontal axis rotation, the CFS group had a higher than normal bias value for the optokinetic (OKN) and eyes open in the dark conditions (p < 0.05), but had normal scores during visual vestibular reflex testing. Five of the 11 subjects had an abnormal OKN bias build up over the course of the run, equal to or actually exceeding the 60 degrees/s target velocity by as much as 14 degrees/s. Altogether, these results are more suggestive of central nervous system deficits than of peripheral vestibular disfunction.

Adult↗

PubMed1995

Otolith function tests in patients with unilateral vestibular lesions.

This study was designed to assess the utility of otolith-ocular reflex testing in patients with complete unilateral peripheral vestibular deficits. Ten subjects were given a clinical vestibular test battery (ENG & vertical rotation) and research oriented tests of otolith function including dynamic posturography with head tilt and earth-horizontal axis rotation with otolith-visual interactions. Clinical tests confirmed the presence of a vestibular deficit and the side of the lesion. The results suggested the following: posturography during head tilt is not a reliable means of detecting unilateral peripheral vestibular dysfunction, while earth-horizontal axis rotation is a reliable means of assessing asymmetric otolith function. The Bias response during earth-horizontal axis rotation was significantly less during rotation ipsilateral to the lesioned ear compared to contralateral rotation while the Mod response was normal. The optokinetic test results in these subjects were normal while otolith-visual interactions were symmetrically reduced in these patients.

Adult↗