Biomedical subjects

M A Wilson

Publications and source records attributed to M A Wilson.

At least 73 records · Page 4Linked to original sources

PubMed1999

Comparative genomics of BCG vaccines by whole-genome DNA microarray.

Bacille Calmette-Guérin (BCG) vaccines are live attenuated strains of Mycobacterium bovis administered to prevent tuberculosis. To better understand the differences between M. tuberculosis, M. bovis, and the various BCG daughter strains, their genomic compositions were studied by performing comparative hybridization experiments on a DNA microarray. Regions deleted from BCG vaccines relative to the virulent M. tuberculosis H37Rv reference strain were confirmed by sequencing across the missing segment of the H37Rv genome. Eleven regions (encompassing 91 open reading frames) of H37Rv were found that were absent from one or more virulent strains of M. bovis. Five additional regions representing 38 open reading frames were present in M. bovis but absent from some or all BCG strains; this is evidence for the ongoing evolution of BCG strains since their original derivation. A precise understanding of the genetic differences between closely related Mycobacteria suggests rational approaches to the design of improved diagnostics and vaccines.

BCG Vaccine↗

PubMed1999

Subacute sepsis impairs vascular smooth muscle contractile machinery and alters vasoconstrictor and dilator mechanisms.

INTRODUCTION: Sepsis results in hyporesponsiveness to alpha-adrenergic stimulation. This is thought to be mediated by the release of vasoactive compounds from the septic endothelium or by the direct effect of sepsis on vascular smooth muscle (VSM) contractile mechanics and machinery. Previous studies have used lethal models of sepsis or endotoxemia to examine this phenomenon. The present study utilizes a clinically relevant, nonlethal model of soft tissue infection to determine the effects of sepsis on alpha-adrenergic mechanisms. We hypothesize that subacute sepsis causes impaired alpha-adrenergic vascular responsiveness by a combination of effects on adrenergic constrictor mechanisms, endogenous dilator tone, and VSM contractile function. METHODS: Male Sprague-Dawley rats underwent implantation of a 2 x 2-cm2 gauze sponge into a subcutaneous pocket created at the base of the tail. Five days after implantation, sepsis (S) was induced by inoculation of the sponge with 10(9) CFU Escherichia coli and Bacteroides fragilis. Controls (C) were inoculated with saline. Thoracic aortic harvest was performed 24 and 48 h after sponge inoculation for organ bath ring studies. Receptor-mediated (phenylephrine) and nonreceptor-mediated (KCl) maximum force of contraction (Fmax) was measured. Vessel sensitivity (pD2) to phenylephrine, acetylcholine, and KCl was calculated from dose-response curves. RESULTS: At 24 h, sepsis resulted in a lower Fmax to phenylephrine (1.15 for C vs 0.5 for S, P < 0.05 by ANOVA), despite an increase in vessel sensitivity (pD2) to alpha-adrenergic stimulation (6.70 for C vs 6.88 for S, P < 0.05 by ANOVA). Fmax to KCl was lower in septic animals at 24 h (3. 50 for C vs 2.77 for S, P < 0.05 by ANOVA) and sensitivity to acetylcholine (pD2) was markedly increased (6.56 for C vs 7.23 for S, P < 0.05 by ANOVA). At 48 h, the impairment in Fmax to alpha-adrenergic stimulation (2.29 for C vs 1.72 for S, P < 0.05 by ANOVA) and KCl (3.5 for C vs 3.08 for S. P < 0.05 vs 24 h C by ANOVA) persisted without any change in sensitivity to phenylephrine or acetylcholine. CONCLUSIONS: Subacute sepsis results in an early suppression of maximum contractile force despite an increase in adrenergic receptor sensitivity (pD2). This may be secondary to an elevation in dilator sensitivity combined with a direct effect of sepsis on VSM contractile mechanisms. Later in the septic process, however, alpha-adrenergic hyporesponsiveness ( downward arrow Fmax) is primarily due to changes in VSM contractile machinery.

Acetylcholine↗

PubMed1999

A Caenorhabditis elegans wee1 homolog is expressed in a temporally and spatially restricted pattern during embryonic development.

A wee1 homolog, wee-1.1, is expressed in both a temporally and spatially restricted pattern during early Caenorhabditis elegans embryogenesis, and is undetectable throughout the remainder of embryogenesis. The wee-1.1 message appears to be zygotically expressed in the somatic founder cell E of the 12-cell embryo. This expression disappears when the E blastomere divides for the first time. The wee-1.1 message then appears transiently in the nuclei of the eight great-granddaughter cells of the AB somatic founder cell, just before these cells divide in the 16-cell embryo. Following this division, the wee-1.1 mRNA is no longer detectable throughout the remainder of embryogenesis. The expression of wee-1.1 in the E blastomere and in the AB progeny appears to be restricted to nuclei in prophase and metaphase of the cell cycle. Analysis of the wee-1.1 mRNA expression pattern in maternal-effect lethal mutants suggests that this expression pattern is restricted to cells of the E and AB fates in the early embryo. This mRNA expression pattern is restricted to a 10-15-min span of embryonic development and may be regulating the timing of crucial cell divisions at this early stage of development.

Amino Acid Sequence↗

PubMed1999

Effects of chronic benzodiazepine exposure on stress-induced neuroactive steroid levels.

Since the neuroactive steroid 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP) has pharmacologic actions similar to benzodiazepine agonists such as diazepam, the influences of chronic diazepam exposure on stress-induced brain levels of 3alpha, 5alpha-THP were examined. Groups of male, female, orchidectomized (ORCH), and ovariectomized (OVX) rats were compared, along with OVX groups given hormone replacement. Chronic diazepam exposure diminished stress-induced brain levels of 3alpha,5alpha-THP and serum corticosterone, although gender, gonadectomy and hormone replacement had disparate influences on these two endocrine responses to stress.

Animals↗

PubMed1999

Dextran sulfate inhibits IFN-gamma-induced Jak-Stat pathway in human vascular endothelial cells.

Human vascular endothelial cells can be induced by IFN-gamma to express class II MHC proteins. Previously, dextran sulfate was shown to selectively inhibit expression of class II MHC by preventing transcription of the gene encoding CIITA, a transactivator protein required for IFN-gamma-inducible expression of class II genes. In this study we characterized the effects of dextran sulfate on the intracellular events occurring prior to CIITA activation. Immunoprecipitation and Western blot analyses indicated that IFN-gamma-induced phosphorylation of Stat1 and Jak2 was blocked by dextran sulfate. In addition, electron micrographs showing the large accumulation of dextran sulfate particles in the cytoplasms of endothelial cells demonstrated that Stat and Jak proteins may directly interact with dextran sulfate. Binding of radiolabeled IFN-gamma to cells indicated that dextran sulfate may also modulate IFN-gamma interactions with the cell surface. Thus, dextran sulfate is capable of interfering with the IFN-gamma-induced expression of class II MHC genes at multiple sites.

DNA-Binding Proteins↗

PubMed1999

Altered vasoconstrictor and dilator responses after a "two-hit" model of sequential hemorrhage and bacteremia.

BACKGROUND: The "two-hit" theory of multiple organ dysfunction (MOD) proposes that an initial insult, such as hemorrhage (HEM), primes the host for an abnormal response to a second stress such as infection. The immunologic/inflammatory component of this theory has been well examined; however, the effects on vascular responsiveness are poorly understood. We hypothesized that HEM primes the vasculature for an altered response to a second pathophysiologic stress. METHODS: Male Sprague-Dawley rats underwent a fixed-volume HEM with resuscitation (H/R) or sham procedure (Sham). At 48 h, animals were given iv E. coli or saline and followed for 1 h. Thoracic aortic rings were then placed in organ baths containing Krebs buffer aerated with 95% O2, 5% CO2. Cumulative dose-response curves to phenylephrine (PHE) and acetylcholine (ACH) were obtained. Maximum force of contraction (Fmax) was measured and pD2 values (receptor sensitivity) were derived. RESULTS: H/R alone resulted in heightened constrictor tone and blunted dilator tone. E. coli reduced Fmax in response to PHE by 50% in Sham vs 76% in H/R. Receptor sensitivity (pD2) to PHE was reduced to a greater degree in H/R (3-fold vs 2-fold). These animals also had a more pronounced enhancement of ACH receptor sensitivity (7-fold vs 2-fold). CONCLUSIONS: Hemorrhage primes the vasculature for an altered response to a subsequent stress. When infection is added as a "second hit," responsiveness to adrenergic agents is diminished and dilator tone is increased. These data may explain the cardiovascular derangements seen clinically in patients who develop MODS after major hemorrhage followed sequentially by infection.

Acetylcholine↗

PubMed1999

Lack of sex differences in anxiety behaviors during precipitated benzodiazepine withdrawal in rats.

Nonprecipitated benzodiazepine (BZ) withdrawal has been reported to increase anxiety levels in rats. The present experiment determined if gender or hormonal status would modulate putative changes in anxiety-related behaviors during precipitated BZ withdrawal in rats. Intact and gonadectomized male and female rats were treated for 4 weeks with empty or diazepam (DZ)-filled silastic capsules. Animals were injected with the BZ antagonist flumazenil (RO15-1788; 5 mg/kg, i.p.) or vehicle, and immediately placed on the elevated plus-maze. Following the 10-min behavioral test, rats were decapitated and trunk blood was collected to measure corticosterone and gonadal hormone levels. During precipitated BZ withdrawal rats showed significantly decreased percent open-arm time; however, this finding was confounded by a significant decrease in activity levels (e.g., closed-arm entries and total-arm entries). Precipitated BZ withdrawal did not significantly attenuate percent open-arm entries, which factors out drug-induced changes in activity levels, compared to vehicle control animals. Overall, the results of this experiment suggest that precipitated BZ withdrawal does not significantly increase anxiety levels when compared to control animals.

Animals↗

PubMed1999

Gender differences in brain and behavior: hormonal and neural bases.

This article briefly discusses the difficulties in determining the brain-behavior relationship and reviews the literature on some potential mechanisms underlying gender differences in behavioral responses. Mechanisms that are discussed include genetic effects, organizational effects of gonadal hormones, genomic actions of steroids, nongenomic effects of steroids, and environmental influences. The review is an introduction to the articles presented in this special volume on gender differences in brain and behavior.

Animals↗

PubMed1999

An analysis of surface roughness, surface morphology and composite/dentin bond strength of human dentin following the application of the Nd:YAG laser.

OBJECTIVES: This study was conducted to investigate the surface effects to dentin following laser "etching" with an Nd:YAG laser, and to determine the shear bond strengths of composite to untreated and laser-treated dentin. METHODS: Dentin surfaces from freshly extracted permanent molar teeth were subjected to laser treatment with an Nd:YAG laser using different laser pulse rates and power settings. The effect of application of a laser enhancing gel was also investigated. Surface profile analysis of the dentin surfaces was undertaken with a perthometer. The results were analysed by SPSS/PC multiple range test. Specimens were examined using a scanning electron microscope (SEM). The shear bond strengths of laser-treated dentin/composite and untreated dentin/composite by conventional dentin bonding (Gold Standard, Chameleon Dental Products) were also determined. These results were also compared by SPSS/PC multiple range test. RESULTS: The laser-treated dentin specimens exhibited a qualitatively different surface morphology when compared with untreated dentin. Laser treatment at higher exposures resulted in the formation of microcracks and fissures. Bonding of resin composite to the laser-treated dentin was not significantly different from untreated dentin despite the fact that the surface roughness of laser-treated dentin was significantly higher than untreated dentin (p < 0.05). SIGNIFICANCE: It was concluded from this study that the etched dentin surfaces produced by the Nd:YAG laser operated under the conditions described were not superior to those obtained with conventional dentin bonding.

Dental Bonding↗

PubMed1999

Complement activation mediates intestinal injury after resuscitation from hemorrhagic shock.

BACKGROUND: Endothelial cell injury after hemorrhage and resuscitation (HEM/RES) might contribute to intestinal hypoperfusion and mucosal ischemia. Our recent work suggests that the injury might be the result of complement activation. We hypothesized that HEM/RES causes complement-mediated endothelial cell dysfunction in the small intestine. METHODS: Male Sprague-Dawley rats (195-230 g) were anesthetized and HEM to 50% of baseline mean arterial pressure for 60 minutes. Just before RES, animals received either soluble complement receptor-1 (sCR1, 15 mg/kg) to inhibit complement activation or saline vehicle. Resuscitation was with shed blood and an equal volume of saline. Two hours after RES, the small bowel was harvested to evaluate intestinal nitric oxide synthase activity (NOS), neutrophil influx, histology, and oxidant injury. RESULTS: HEM/RES induced tissue injury, increased neutrophil influx, and reduced NOS activity by 50% (vs. SHAM), all of which were completely prevented by sCR1 administration. There were no observed differences in oxidant injury between the groups. CONCLUSION: Histologic tissue injury, increased neutrophil influx, and impaired NOS activity after HEM/RES were all prevented by complement inhibition. Direct oxidant injury did not seem to be a major contributor to these alterations. Complement inhibition after HEM might ameliorate reperfusion injury in the small intestine by protecting the endothelial cell, reducing neutrophil influx and preserving NOS function.

Animals↗

PubMed1999

Cerebrovascular disease as a general medicine discharge diagnosis: assessment of diagnostic agreement on case note review.

BACKGROUND: Accurate clerical coding of discharge diagnoses is important partly because results may be used to derive a recommended costing for hospital length of stays (LOS). Some authors think that discharge coding undertaken by clinicians will result in less diagnostic misclassification than clerical coding. This presupposes a high degree of between-observer diagnostic agreement between clinicians. AIMS: To compare discharge coding undertaken by two general physicians, for patients receiving a clerical discharge code of cerebrovascular disease. The recommended LOS was then calculated from each observer's discharge codes using the Physicians Diagnosis Related Group Working Guidebook. RESULTS: Eighty-two cases were coded as stroke by the clerical coder. Both medical coders agreed with this diagnosis in 68 (83%) of these cases. The corresponding figure for cases coded by the clerical coder as transient cerebral ischaemia was 47% (32/68) agreement between all three observers. Correcting for chance agreement between medical observers using the kappa statistic, a value of 0.64 was obtained for the combined stroke and transient cerebral ischaemia discharges, suggesting moderate diagnostic agreement. Using the clerical coder's results, the mean recommended LOS for all cases of cerebrovascular disease over the study period was calculated at 6.68 days. The corresponding values for the two medical coders were 6.68 days and 6.75 days. CONCLUSIONS: Diagnostic agreement between clinicians was moderate. Consideration of alternative diagnostic possibilities and the difficulty in determining the duration of neurological deficit were the main reasons for diagnostic disagreement. The mean recommended LOS was similar, however, when comparing results from all three observers.

Adult↗

PubMed1999

Pap screening clinics with native women in Skidegate, Haida Gwaii. Need for innovation.

PROBLEM ADDRESSED: First Nations women in British Columbia, especially elders, are underscreened for cancer of the cervix compared with the general population and are much more likely to die of the disease than other women. OBJECTIVE OF PROGRAM: To develop a pilot program, in consultation with community representatives, to address the Pap screening needs of First Nations women 40 years and older on a rural reserve. MAIN COMPONENTS OF PROGRAM: Identification of key links to the population; consultation with the community to design an outreach process; identification of underscreened women; implementation of community Pap screening clinics; evaluation of the pilot program. CONCLUSIONS: We developed a Pap screening outreach program that marked a departure from the usual screening approach in the community. First Nations community health representatives were key links for the process that involved family physicians and office staff at a local clinic on a rural reserve. Participation rate for the pilot program was 48%, resulting in an increase of 15% over the previously recorded screening rate for this population. More screening clinics of this type and evaluation for sustainability are proposed.

Adult↗

PubMed1999

A short-term clinical evaluation of a tricure glass-ionomer system as a transitional restoration and core buildup material.

OBJECTIVE: A general dental practice study investigated the use of a resin-modified glass ionomer material as a transitional restoration and as a core buildup material. The study also assessed a resin-modified glass-ionomer luting system. METHOD AND MATERIALS: Fifty-one badly broken-down vital permanent molar teeth in 44 patients were restored. No dentin pins were placed; however, preexisting pins were retained in 7 teeth. Following baseline and 3-month assessments, complete veneer gold crowns were placed on the selected teeth. The preparations involved ferruling in sound tooth tissue. The completed crowns were reviewed 3 and 12 months after placement. Modified US Public Health Service criteria were used for assessment throughout. Clinical assessment was complemented by examination of photographic records and replicas obtained from silicone impressions. RESULTS: All 51 transitional restorations were found to be clinically satisfactory at the 3-month review. Nineteen (37%) transitional restorations had limited defects that were eliminated in crown preparation. Of the 51 permanent crowns, 46 (90%) were reviewed at 3 months and 44 (86%) at 1 year. All the crowns reviewed at 3 and 12 months were clinically satisfactory. The luting system investigated showed favorable handling characteristics and excellent short-term performance. CONCLUSION: The materials investigated are, over a period of at least 12 months, effective in the restoration of broken-down molar teeth destined to be crowned. With the use of these materials and ferruling, the use of dentin pins may be unnecessary in selected cases.

Adolescent↗

PubMed1999

A three-year evaluation of restorations placed with a smear-layer-mediated dentin bonding agent in non-carious cervical lesions.

PURPOSE: To evaluate the handling characteristics, clinical behavior, and effectiveness of Coltene ART Bond/Brilliant restorations in mixed Class V preparations in maxillary premolar and canine teeth of adult patients over a three-year period. MATERIALS AND METHODS: Single-center, uncontrolled, clinical evaluation of 50 restorations in 26 patients extending over 36 months. RESULTS: At three years, 34 restorations, or 68% of those originally placed, in 20 patients were available for review. One of the 34 restorations had been lost 15 months after placement. In terms of marginal integrity and staining, anatomic form, surface texture and staining, and postoperative sensitivity, over 90% of the restorations reviewed at three years were rated alpha. Following difficulties in obtaining excellent color match in relation to 14 (28%) of the restorations at the time of placement, only 44% of the restorations were rated alpha at three years. CONCLUSION: It was concluded that with the possible exception of excellent color match, ART Bond/Brilliant restorations may be found to perform favorably in mixed Class V lesions in selected adult patients over a period of at least three years. The findings indicate that resin composite restorations placed with a smear-layer mediated dentin bonding agent may be found to have a favorable clinical outcome in non-carious cervical lesions.

Adult↗

PubMed1998

IL-10 gene transfer to intracranial 9L glioma: tumor inhibition and cooperation with IL-2.

This study examines the effects of interleukin-10 (IL-10) and combination IL-10 + IL-2 gene transfer on experimental brain tumor growth in vivo. 9L gliosarcoma cells were engineered to stably express murine IL-10 (9L-IL-10 cells) and implanted subcutaneously or to the caudate/putamen of syngeneic rats. The growth of tumors expressing IL-10 was substantially reduced compared to that of control tumors (p < 0.05). Intracranial tumors expressing IL-10 and IL-2 were established by co-implanting 9L-IL-10 cells with endothelial cells engineered to express IL-2. At 14 days post-implantation, tumors expressing IL-10 + IL-2 were 99% smaller than control-transfected tumors (p < 0.0001). This extent of anti-tumor effect could not be achieved by expression of IL-10 or IL-2 alone within tumors. Neither IL-10 nor a combination of IL-10 + IL-2 gene delivery inhibited tumor growth in severe combined immunodeficient (SCID-Beige) mice (p > 0.05). Immunohistochemical analysis revealed that IL-10 + IL-2 gene delivery markedly increased T-cell infiltration within the striatum ipsilateral to tumor cell implantation. These findings establish that IL-10 expression, particularly in combination with IL-2 expression, can have significant immune-dependent anti-tumor actions within intracranial gliomas.

Animals↗

PubMed1998

Concentrations of anesthetics across the water-membrane interface; the Meyer-Overton hypothesis revisited.

The free energies of transferring a variety of anesthetic and nonanesthetic compounds across water-oil and water-membrane interfaces were obtained using computer simulations. Anesthetics exhibit greatly enhanced concentrations at these interfaces, compared to nonanesthetics. The substitution of the interfacial solubilites of the anesthetics for their bulk lipid solubilities in the Meyer-Overton relation, was found to give a better correlation, indicating that the potency of an anesthetic is directly proportional to its solubility at the interface.

Algorithms↗

PubMed1998

A statistical paradigm for neural spike train decoding applied to position prediction from ensemble firing patterns of rat hippocampal place cells.

The problem of predicting the position of a freely foraging rat based on the ensemble firing patterns of place cells recorded from the CA1 region of its hippocampus is used to develop a two-stage statistical paradigm for neural spike train decoding. In the first, or encoding stage, place cell spiking activity is modeled as an inhomogeneous Poisson process whose instantaneous rate is a function of the animal's position in space and phase of its theta rhythm. The animal's path is modeled as a Gaussian random walk. In the second, or decoding stage, a Bayesian statistical paradigm is used to derive a nonlinear recursive causal filter algorithm for predicting the position of the animal from the place cell ensemble firing patterns. The algebra of the decoding algorithm defines an explicit map of the discrete spike trains into the position prediction. The confidence regions for the position predictions quantify spike train information in terms of the most probable locations of the animal given the ensemble firing pattern. Under our inhomogeneous Poisson model position was a three to five times stronger modulator of the place cell spiking activity than theta phase in an open circular environment. For animal 1 (2) the median decoding error based on 34 (33) place cells recorded during 10 min of foraging was 8.0 (7.7) cm. Our statistical paradigm provides a reliable approach for quantifying the spatial information in the ensemble place cell firing patterns and defines a generally applicable framework for studying information encoding in neural systems.

Action Potentials↗

PubMed1998

Expression of NMDA receptor subunit mRNA after MK-801 treatment in neonatal rats.

Although NMDA receptor antagonists are neuroprotective when delivered in conjunction with NMDA, supersensitivity to NMDA-mediated injury follows dizocilpine (MK-801) administration in neonatal rats. An increase in NMDA-sensitive [3H]-glutamate binding accompanies the increase in vulnerability to excitotoxic injury. The present study tests the hypothesis that MK-801 may alter gene expression for the NMDA receptor subunits. Quantitative in situ hybridization histochemistry was used to evaluate the expression of NMDA receptor subunits NR1 and NR2A-D in neonatal rats, 2 to 4 h after treatment with MK-801. Increased mRNA for multiple NMDA receptor subunits was observed in cerebral cortex, striatum and hippocampus. The percent increase in NR2A mRNA was larger than the percent change in NR1, NR2B or NR2D. A small increase in mRNA for the metabotropic glutamate receptor mGluR5 was also observed after MK-801 treatment. These results indicate that gene expression for NMDA receptor subunits in the developing brain is rapidly altered after antagonist exposure. Increased expression of excitatory amino acid receptor subunit mRNA may contribute to the enhanced vulnerability to excitotoxic injury that has been observed after MK-801 treatment.

Animals↗