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Biomedical subjects

M A Wilson

Publications and source records attributed to M A Wilson.

At least 199 records · Page 11Linked to original sources
PubMed1993

Microvascular vasoconstriction and mucosal hypoperfusion of the rat small intestine during bacteremia.

Our previous studies have demonstrated that bacteremia induces vasoconstriction and hypoperfusion of the small intestinal microcirculation. The present study used time-transit doppler flowmetry, intravital microscopy, and laser doppler fluximetry to measure superior mesenteric artery (SMA) blood flow, intestinal microvascular blood flow, and mucosal perfusion. The aim of this study was to determine the relative importance of the intestinal macro- and microcirculations in the development of mucosal hypoperfusion. Animals were infused with 5 x 10(8) colony-forming units of Escherichia coli/100 g body weight or saline as control. Bacteremia induced a normotensive, normodynamic state. SMA blood flow was unaffected by bacteremia, but arteriolar vasoconstriction (approximately -30%) and microvascular hypoperfusion (approximately -70%) occurred. Mucosal perfusion decreased by 40% from baseline, and was temporally correlated with microvascular hypoperfusion. From these data, we conclude that the microcirculation has a central role in the development of mucosal hypoperfusion during bacteremia.

Animals↗
PubMed1993

Divergent alterations in gamma-aminobutyric acid responses of male and ovariectomized rats after chronic benzodiazepine agonist exposure: analysis of gamma-aminobutyric acid-activated chloride influx.

Gonadal status in rats modulates the development of tolerance to the anticonvulsant effects of the benzodiazepines and the concomitant changes in cortical gamma-aminobutyric acid (GABA)A receptors after chronic benzodiazepine agonist exposure. The present study analyzed physiological GABA responsiveness after chronic benzodiazepine exposure by measuring GABA-activation of 36chloride influx into cortical and cerebellar microsacs. GABA-stimulated 36chloride influx was compared in groups of male and ovariectomized female rats after acute (2-3 day) or chronic (3 week) exposure to diazepam-filled or empty silastic implants. Chronic diazepam exposure increased cortical GABA-activated 36chloride influx in ovariectomized rats, but did not influence GABA responses in males. Acute exposure to diazepam did not alter cortical 36chloride influx in either hormone group. Vehicle-treated ovariectomized rats also had lower levels of cortical GABA-activated 36chloride influx than vehicle-treated males. In cerebellar microsacs, diazepam exposure enhanced GABA-induced 36chloride influx. This effect was observed after both acute and chronic treatments and hormone groups did not differ in their response to chronic benzodiazepine exposure. Enhancement of GABA-stimulated 36chloride influx by the benzodiazepine agonist midazolam was not altered in male or ovariectomized rats after chronic diazepam treatment. Thus, gonad-related factors influence the changes in GABAA receptors and the resulting GABA responses in the cortex, but not the cerebellum, observed after chronic benzodiazepine agonist exposure in rats. These regionally specific divergent alterations in GABAergic systems may be related to the differential development of tolerance to the anticonvulsant effects of the benzodiazepines observed in these hormone groups.

Animals↗
PubMed1993

Divergent alterations in gamma-aminobutyric acid/benzodiazepine responses of male and ovariectomized rats after chronic benzodiazepine agonist exposure: electrophysiological analysis of substantia nigra pars reticulata neurons.

Gonadal status in rats modulates both the apparent development of tolerance to the anticonvulsant effects of the benzodiazepines and the concomitant changes in cortical gamma-aminobutyric acid (GABA)A receptors and GABA-activated 36chloride flux after chronic exposure to a benzodiazepine agonist. By using single-unit electrophysiological techniques, the present study demonstrates disparate neural adaptations in the substantia nigra pars reticulata (SNr) of anesthetized male and ovariectomized (OVX) rats after chronic (3 week) exposure to a benzodiazepine agonist. Unlike males, no reduction in SNr responsiveness to systemically administered diazepam was seen in OVX females after chronic treatment with diazepam-filled implants. In addition, OVX females did not show the compensatory increase in spontaneous firing rate observed in males upon administration of the specific benzodiazepine antagonist, RO15-1788. Sensitivities to locally (microiontophoretically) applied GABA, benzodiazepine agonist (midazolam) and GABA antagonist (SR95531) were not affected by hormone-related factors or chronic exposure to diazepam-filled implants. These results indicate that male and OVX rats show divergent alterations in SNr responses to systemic administration of benzodiazepines after chronic benzodiazepine treatment which appear unrelated to intrinsic changes in responsiveness of the GABA/benzodiazepine receptor complex.

Animals↗
PubMed1992

Changes in rates of protein synthesis and eukaryotic initiation factor-4 inhibitory activity in cell-free translation systems of sea urchin eggs and early cleavage stage embryos.

The characteristics of cell-free translation systems prepared from unfertilized eggs and early cleavage stage embryos of the sea urchin, Strongylocentrotus purpuratus, closely reflect the developmentally regulated changes in protein synthesis initiation observed in vivo. Cell-free translation systems prepared over the first 0-6 h following fertilization show gradually increasing activities, mimicking the changes observed in vivo. The mechanisms underlying these increases are complex and occur at several levels. One factor contributing to the rise in protein synthetic rate is the gradual increase in eukaryotic initiation factor (eIF)-4 activity. This is correlated with the progressive inactivation of an inhibitor of eIF-4 function, which can be reactivated by in vitro manipulations. The relatively slow activation of eIF-4 follows similar kinetics to the increased utilization of maternal mRNA and ribosomes, in contrast to the rapid rise in maternal mRNA activation, and the increase in eIF-2B activity. This slow release from eIF-4 inhibition following a rapid release from eIF-2B inhibition and increased mRNA availability is reflected in the pattern of initiator tRNA binding to the small ribosomal subunit observed in cell-free translation systems. In translation systems from unfertilized eggs, initiator tRNA is unable to interact with the small ribosomal subunit, consistent with an initial block in both eIF-2B and eIF-4 activity. In translation systems from 30-min embryos, 48 S preinitiation complexes accumulate, reflecting the release from inhibition of mRNA availability and eIF-2B activity, but continued low activity of eIF-4. The accumulation of initiator tRNA in 48 S preinitiation complexes disappears gradually in translation systems from later embryos, as eIF-4 is slowly released from inhibition.

Animals↗
PubMed1992

Effects of gender and gonadectomy on responses to chronic benzodiazepine receptor agonist exposure in rats.

Gonadal steroid hormones or their derivatives have been shown to modulate the GABA receptor complex and GABA-mediated responses in a manner similar to the benzodiazepines. The present study examines if hormonal status modulates the development of tolerance and/or the neural adaptations in GABAA receptors associated with chronic benzodiazepine exposure. Anticonvulsant effects of diazepam were compared in groups of male, female, orchidectomized, and ovariectomized rats following acute (3 day) and chronic (3 week) exposure to diazepam-filled silastic implants. Results indicated that hormonal status did not significantly modify either the neural levels of drug resulting from the diazepam implants or the diazepam-induced increases in bicuculline seizure thresholds following acute (3 day) exposure. Unlike males and gonad-intact females, ovariectomized rats continued to display elevated seizure threshold values due to the diazepam released from the implants even after chronic diazepam exposure. This suggests that the tolerance to benzodiazepine actions observed in male and intact female rats was prevented by ovariectomy. Analysis of the anticonvulsant effects of additional challenge doses of diazepam in chronic diazepam-treated rats paradoxically suggested that benzodiazepine tolerance developed in all hormone groups. The discrepancies between these two tests of anticonvulsant tolerance may be related to the divergent neural GABAA receptor adaptations seen between hormone groups. Ovariectomized rats displayed a reduction in GABA IC50 values for [3H]bicuculline-thiocyanate binding in cortex following chronic diazepam exposure that was not observed in males or intact females. These results suggest that the diminution of ovarian steroid hormones may modulate the neural GABAergic changes associated with the development of tolerance to benzodiazepine actions during chronic agonist exposure.

Animals↗
PubMed1992

Determination of bone mineral density by dual x-ray absorptiometry in patients with uncemented total hip arthroplasty.

Bone remodeling is an expected sequela with total hip arthroplasty (THA). Although there are several methods of estimating bone response in THA patients from radiographs, there are no accurate and generally accepted methods for quantitative determinations in vivo. In this study, we describe an application of dual x-ray absorptiometry (DXA) for measuring bone mineral content and bone mineral density in the proximal femur following THA. DXA is a noninvasive technique with minimal radiation exposure (< 5 mrem). Various aspects of measurement error (accuracy and reliability) of this application of DXA were determined in a series of studies reported here. Accuracy error (how similar are the measured and actual values) was < 1% determined in bone phantoms of four densities. Precision error (how reproducible are the measurements) was also < 1% at all four densities in the phantoms and was only slightly elevated (0.9-1.5%) in repeated measurements of implanted cadaver femora. Precision error in vivo, determined both from multiple replicates on five patients and from duplicate scans on 30 patients, was further elevated but remained < 5%. Contributions to precision error, rotation of the leg, and interoperator variability were assessed; none was found to elevate precision error appreciably. We suggest that DXA is a feasible method for quantifying bone response following THA, and will allow discrimination of small changes (> 5%) not previously measurable.

Absorptiometry, Photon↗
PubMed1992

Regeneration in the Xenopus tadpole optic nerve is preceded by a massive macrophage/microglial response.

Changes in the optic nerve following a crush lesion and during axonal regeneration have been studied in Xenopus tadpoles, using ultrastructural and immunohistological methods. Degeneration of both unmyelinated and myelinated axons is very rapid and leads to the formation, within 5 days, of a nerve which consists largely of degeneration debris and cells. Immunohistological analysis with monoclonal antibody 5F4 shows that there is a rapid and extensive microglial/macrophage response to crush of the nerve. Regenerating axons have begun to enter the distal stump by 5 days and grow along the outer part of the nerve in close approximation to the astrocytic glia limitans. Between 5 and 10 days after nerve crush, regenerating axons reach and pass the chiasma. Macrophages are seen in the nerve at the site of the lesion within 1 h, and the response peaks between 3-5 days, just before axonal regeneration gets under way.

Animals↗
PubMed1992

Influences of gender, gonadectomy, and estrous cycle on GABA/BZ receptors and benzodiazepine responses in rats.

Benzodiazepines (BZ) and steroid hormone derivatives can potentiate the inhibitory actions of GABA through interactions with the GABAA/BZ/chloride ionophore complex. The present study examines whether the in vivo hormone milieu of rats modulates GABA/BZ receptors and/or benzodiazepine responses. The influences of gender, estrous cycle, and the diminution of steroid levels on GABA/BZ receptors and BZ anticonvulsant responses were tested by comparing these parameters in groups of intact male, intact female, orchidectomized, and ovariectomized rats. The hormonal milieu appears to modulate the GABA recognition site and possibly GABA-related responses in rats. This is evidenced by the decrease in cortical GABAA receptor affinity seen in females compared with other hormone groups and the gender-related difference observed in susceptibility to seizures induced by the GABA antagonist bicuculline. In cycling females, high circulating levels of progesterone were correlated with heightened seizure thresholds, suggesting that progestins serve a protective role in the control of seizure activity. Although a gender-related difference in cortical BZ binding affinity was observed, BZ receptor parameters in several other brain areas and BZ anticonvulsant responses were unaffected by physiological fluctuations in gonadal hormones.

Animals↗
PubMed1992

The Julius F. Neumueller Award in Optics, 1989: change of pupil centration with change of illumination and pupil size.

Pupil centration is important to the optical blur on the retina. Using a dual Maxwellian view system we measured the centration of the pupil with respect to the achromatic axis of the eye as a function of pupil size. Significant shifts of the pupil center (up to 0.6 mm) with pupil dilation were measured in both nasal and temporal directions. The effect was usually symmetrical between the two eyes and the shift was linear with pupil size in one-half of the subjects. From their initial positions the linear pupil center shifts with dilation were in the direction of the achromatic axis.

Analysis of Variance↗
PubMed1992

Contribution of antibody in normal human serum to early deposition of C3 onto encapsulated and nonencapsulated Cryptococcus neoformans.

Encapsulated and nonencapsulated cryptococci differ in their activation of the complement system. Incubation of nonencapsulated cryptococci in normal human serum (NHS) initiates both the classical and alternative pathways. This activation is characterized by an immediate, synchronous activation and binding of C3 to the yeast cells. Encapsulated cryptococci activate only the alternative pathway. This activation is characterized by a delayed (4 to 5 min), asynchronous activation and binding of C3. We examined the properties of antibodies in NHS that mediate immediate, synchronous binding of C3 to nonencapsulated cryptococci and zymosan. Adsorption of NHS with nonencapsulated cryptococci or zymosan produced a 4- to 6-min delay in the kinetics for activation and binding of C3 from the adsorbed serum to each respective yeast cell. This delay was similar to the delay observed when nonencapsulated cryptococci or zymosan was incubated in NHS in which the classical pathway was blocked by chelation of Ca2+. Proteins bound to serum-treated nonencapsulated cryptococci or zymosan were eluted and found to be predominantly immunoglobulin G (IgG), with lesser amounts of IgM. The eluted IgG could restore to adsorbed serum the rapid early kinetics for activation and binding of C3 characteristic of classical pathway initiation. Cross-adsorption showed that there was considerable cross-reactivity between the antibodies which restored rapid, early activation kinetics to NHS adsorbed with zymosan or nonencapsulated cryptococci. Encapsulated cryptococci were unable to adsorb the antibodies from NHS that mediated the rapid, early activation and binding of C3 to zymosan and nonencapsulated cryptococci. The latter results show that occlusion of antigenic sites at the cryptococcal cell wall is a newly recognized property that can be added to the repertoire of biological activities of the cryptococcal capsule.

Adsorption↗
PubMed1992

Kinetic analysis of the amplification phase for activation and binding of C3 to encapsulated and nonencapsulated Cryptococcus neoformans.

Encapsulated and nonencapsulated cryptococci exhibit quantitative and qualitative differences in their activation of the complement system. We examined the kinetics for the rapid amplification phase in which C3 was activated and bound to encapsulated cryptococci, nonencapsulated cryptococci, and zymosan particles. Yeast cells were incubated in normal human serum containing 125I-labeled C3, and bound C3 fragments were measured after 1 to 64 min of incubation. A kinetic analysis showed that the apparent first-order rate constant (k') for binding of C3 to nonencapsulated cryptococci did not differ significantly from k' for binding of C3 to zymosan particles (P greater than 0.05). However, the rate constant for binding of C3 to encapsulated cryptococci was significantly (P less than 0.001) greater than k' for binding of C3 to nonencapsulated cryptococci and zymosan particles. A plot of C3 molecules bound to encapsulated cryptococci versus time cubed was nearly linear, suggesting that accumulation of C3 in the cryptococcal capsule follows the kinetics predicted by an expanding sphere. In contrast, the plot of C3 molecules bound to nonencapsulated cryptococci or zymosan particles against time was nearly linear, but those plots against time squared or time cubed were not. This result indicates that the rate-limiting step for the addition of C3 fragments to these latter yeast cells follows the kinetics of neither the perimeter of an expanding circle nor the surface of an expanding sphere. Taken together, the results indicate that the high rate of accumulation of C3 in the cryptococcal capsule is consistent with the expected geometry of an expanding sphere of bound C3 within the three-dimensional matrix of the capsule.

Complement Activation↗
PubMed1992

Comparison of DNA fingerprints and somatic serotypes of serogroup B and E Pasteurella multocida isolates.

The DNA fingerprint profiles and somatic serotypes of 71 Pasteurella multocida capsule serogroup B isolates, 13 capsule serogroup E isolates, and 16 somatic reference serotype strains were compared. Each of the 16 reference somatic serotypes had a unique DNA fingerprint profile with the HhaI restriction endonuclease. Fifty-four serogroup B isolates (isolated from classical cases of hemorrhagic septicemia) reacted with somatic serotype 2 or 5 antiserum and had DNA fingerprint profiles which resembled that of the serotype 2 reference strain. Seven DNA fingerprint profiles were found among 16 serogroup B strains representing other somatic serotypes. The DNA fingerprints of these isolates were different from the fingerprints of the 16 somatic reference serotype strains. All 13 serogroup E isolates had identical somatic serotypes and identical DNA fingerprint profiles when the HhaI endonuclease was used. The HhaI fingerprint profile of the serogroup E isolates did not match any fingerprint profile of the reference somatic serotype strains. Following DNA profiling with the HhaI endonuclease, the 13 serogroup E isolates were differentiated sequentially with HpaII restriction endonuclease. A descriptive identification epithet for P. multocida isolates was constructed. The descriptive epithet consists of serologic identification and sequential DNA profiles with restriction endonucleases HhaI and HpaII, respectively. DNA fingerprinting of P. multocida is a precise characterization method. In conjunction with serologic typing, it can further classify P. multocida isolates for epidemiologic studies.

Animals↗
PubMed1992

Persistence of abnormalities in metabolism of apolipoproteins B-100 and A-I after weight reduction in patients with primary hypertriglyceridemia.

Obesity commonly accompanies hypertriglyceridemia, and weight reduction is widely recommended for treatment of elevated triglyceride levels. To determine whether weight reduction will normalize lipoprotein metabolism in overweight, hypertriglyceridemic patients, 10 such male patients underwent weight loss until their body weights were within the desirable range. After reestablishment of a steady state in body weight at the lower level, measurements were made of plasma lipid, lipoprotein, and apolipoprotein levels and the kinetics of low density lipoprotein (LDL) apolipoprotein B-100 (apo B) and apolipoprotein A-I (apo A-I). The patients lost an average of 10.6 +/- 2.1 kg (mean +/- SEM). Plasma triglyceride concentrations fell from 431 +/- 42 mg/dl to 248 +/- 27 mg/dl (p less than 0.001), whereas concentrations of total cholesterol, LDL cholesterol, total apo B, and high density lipoprotein (HDL) cholesterol were unchanged after weight loss. On average, the fractional catabolic rates (FCRs) for LDL were much higher in the patients after weight loss than in 16 normal control subjects (0.55 +/- 0.06 versus 0.31 +/- 0.06 pool/day), and input rates for LDL also were higher for hypertriglyceridemic patients after weight loss (22.2 +/- 2.4 versus 12.8 +/- 2.3 mg/kg.day). Compared with 20 normal control subjects, hypertriglyceridemic patients after weight reduction had persistent low HDL cholesterol levels (32 +/- 2 versus 54 +/- 3 mg/dl) as well as low apo A-I levels (99 +/- 5 versus 122 +/- 4 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Prevalence and serovars of leptospira involved in equine abortions in central Kentucky during the 1990 foaling season.

A study to determine the prevalence of leptospira-induced abortions in the central Kentucky equine population during the 1990 foaling season and to determine the leptospira serovars responsible was conducted. From July 1, 1989 through June 30, 1990, 32 (4.4%) of 726 submissions (fetuses, stillborn foals, and/or placentas) were diagnosed as leptospirosis by the fluorescent antibody test and/or microscopic agglutination test. Attempts were made to isolate leptospires from the fetal tissues and/or the dam's urine in 31 of these cases. Leptospira interrogans serovar kennewicki was isolated from 11 (35.5%) and serovar grippotyphosa from 2 (6.5%) of the 31 cases. Of 12 cases that were culture negative with serologically positive fetal fluids, 8 had titers against serovar pomona, 1 against bratislava, 1 against grippotyphosa, 1 against hardjo, and 1 against both bratislava and pomona.

Abortion, Veterinary↗
PubMed1992

Home from hospital: a survey of hospital discharge arrangements in Northamptonshire.

The timeliness and adequacy of inpatient discharge communication between hospitals and general practitioners (GPs) in Northamptonshire was examined by a postal questionnaire survey of GPs of patients recently discharged from hospital, with the aim of improving the co-ordination of discharge procedures, and hence improving continuity of care. The questionnaire measured when and how the GP was informed of the discharge, and examined the adequacy of medical, therapeutic and social details in the discharge documents sent out by the hospital. It was found that 67 per cent of discharges had been notified to the GP by the hospital within five days of discharge. With notable exceptions the discharge documents were considered timely. General practitioners were less satisfied with the adequacy of discharge communication in terms of 'social' topics such as transport needs, social services back-up, and whether a patient with a malignancy knew about his or her diagnosis. The GPs of patients under geriatricians were more satisfied with the quality of discharge documents. Comparison with an earlier study suggested that the speed of communication and involvement of GPs in discharge in Northamptonshire is not as satisfactory as that found in Oxford in 1986. It was concluded that within the county there appear to be models of good practice in terms of discharge communication with GPs. These standards should be adopted by other specialties to match or improve on existing good practice.

Aftercare↗
PubMed1992

Pentoxifylline preserves small-intestine microvascular blood flow during bacteremia.

BACKGROUND: Intestinal mucosal ischemia with subsequent mucosal dysfunction has been implicated in the pathogenesis of ongoing sepsis and multiple systems organ failure. We have previously reported vasoconstriction and hypoperfusion in the intestinal microcirculation during sepsis. Efforts to improve microcirculatory blood flow during sepsis may lead to more effective treatment or prevention of multiple systems organ failure. Pentoxifylline improves survival and visceral organ perfusion in experimental sepsis and hemorrhage. The purpose of this study was to determine whether pentoxifylline would improve microvascular blood flow in the small intestine during bacteremia. METHODS: In vivo videomicroscopy was used to quantitate alterations of the small-intestine microcirculation during Escherichia coli bacteremia in rats pretreated with either intravenous pentoxifylline or saline solution. Systemic hemodynamic and microvascular variables were measured every 15 minutes for 2 hours. RESULTS: Tachycardia and increased cardiac output developed in bacteremic rats while they remained normotensive. Intestinal vasoconstriction and hypoperfusion occurred in bacteremic rats treated with saline solution. Microvessel diameters and blood flow remained within 5% to 10% of baseline in bacteremic rats pretreated with pentoxifylline. Pentoxifylline in nonbacteremic rats resulted in intestinal vasodilation and increased blood flow. CONCLUSIONS: Pentoxifylline prevented small-intestine vasoconstriction and preserved microvascular blood flow during hyperdynamic sepsis. Pentoxifylline in nonbacteremic rats increased microvascular blood flow.

Animals↗
PubMed1991

Dexfenfluramine neurotoxicity in brains of non-human primates.

Dexfenfluramine, a drug prescribed for appetite suppression, was evaluated in non-human primates for its potential to produce toxic effects on brain serotonin (5-HT) neurons. Squirrel monkeys received dexfenfluramine subcutaneously twice daily for four days at doses of 1.25 or 5.00 mg/kg. Two weeks later, a dose-related depletion of 5-HT and 5-hydroxyindoleacetic acid was found, together with a reduced number of 5-HT uptake sites. Morphological studies showed acute pathological changes in 5-HT axons, followed by a persistent decrease in 5-HT axon density. Our findings indicate that dexfenfluramine damages central 5-HT neurons in monkeys and raise concern about the potential neurotoxicity of this drug in man.

Animals↗