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Biomedical subjects

M R Powell

Publications and source records attributed to M R Powell.

At least 19 recordsLinked to original sources

A potential strategy for decreasing milk production in the ewe at weaning using a growth hormone release blocker.

Following the loss or removal of ewes' lambs, ewes frequently continue to lactate for a short time, which potentially predisposes them to mastitis. Therapies that stop or reduce milk production in such situations would be beneficial. Milk production in ruminants is positively correlated with serum concentrations of growth hormone (GH). We sought to determine whether methscopolamine bromide (MB), an anticholinergic agent reported to block GH secretion, would selectively and reversibly reduce milk yield in lactating ewes. White-face ewes (n = 24) that were nursing lambs were assigned on d 59 +/- 2 postpartum (d 0) to receive s.c. injections of 96 mg of MB on d 2, 3, and 4 (1630). On d 0, 2, 5, and 7 (0900), ewes were sequentially separated from their lambs, treated with 40 IU oxytocin, and 30 s later were milked. Ewes remained separated from their lambs for 6 h, after which (1500) ewes were again milked and quantity of milk was determined. Milk yields at d 0, 2, 5, and 7 were 267 +/- 16.9, 266 +/- 15.5, 225 +/- 11.9, and 244 +/- 13.4 g, respectively. It was concluded that treatment of ewes with MB reduced milk yield (P < .01), and the effect was reversible. A second experiment was performed to determine the acute effects of MB on serum concentrations of GH. Hampshire ewes (n = 14) that were nursing lambs were assigned on d 55 +/- 1 postpartum to receive a.s.c. injection of saline (n = 7) or 96 mg of MB (n = 7) at min 0.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Blood donors in a vector-free zone of Ecuador potentially infected with Trypanosoma cruzi.

Chagas' disease is a serious health problem for the population of South and Central America. Blood transfusion is the second most common way in which this disease is transmitted. Several studies have reported finding Trypanosoma cruzi-infected blood in blood banks in endemic areas. Serum samples were taken from the Red Cross blood bank in Quito, a nonendemic and vector free zone of Ecuador, in December 1992 and May 1993 and analyzed by enzyme-linked immunosorbent assay using crude epimastigote extract from the Brazil strain of T. cruzi. Of 162 samples examined in December 1992, 12.1%, 13.9%, and 74% were seropositive, indeterminate, and seronegative, respectively. Of 173 samples taken in May 1993, 6.2%, 17.9%, 75.9% were seropositive, indeterminate, and seronegative, respectively. Western blot analysis of these sera using sodium dodecyl sulfate-polyacrylamide gel electrophoresis with 7.5% gels separated T. cruzi epimastigote antigen proteins, and revealed a reaction with a 205-kD doublet antigen with most of the seropositive samples. These results indicate the necessity for long-term screening of blood bank donors to reduce the risk of transfusion transmission of the disease even in areas of endemic countries where the vector is not present.

Animals

Inverted immersion as a novel gravitoinertial environment.

BACKGROUND: Inverted immersion (II) offers a unique opportunity to swing the orientation of the gravity vector 180 degrees from its usual configuration with vestibular end organs. During II, extrathoracic fluid dynamics are identical to those of upright immersion (UI). II exposes individuals to a novel gravitoinertial environment and, therefore, should produce motion sickness (MS). HYPOTHESIS: II is more provocative of signs and symptoms of MS than UI. METHODS: Nine subjects were exposed once to II and UI. Conventional SCUBA gear was worn. In II, the subject wore a wetsuit which provided 5-7 kg force of positive buoyancy and, with no weight belt, caused him to float while inverted against the underside of a platform. An experiment with UI was identical except that a weight belt was worn which provided 5-7 kg force of negative buoyancy, and the subject stood upright against the bottom of the pool. The experiment was terminated after 3 hours or "upon the onset of the first, clear, persistent feeling of nausea", whichever came first. Throughout the experiment the subject rotated through a series of tasks: assembly of a pipe puzzle, performance of a series of head movements, and ambulation. Immediately post-dive, postural stability was assessed with tandem standing with and without eyes closed and with and without the neck extended 45 degrees. A questionnaire regarding susceptibility to motion sickness was completed pre-dive. RESULTS: No subject terminated the test because of MS during UI; seven subjects terminated the test during II (p < 0.025, McNemar's test). Posture was less stable after II than after UI (p < 0.05, sign test). MS questionnaire results did not predict susceptibility to II. CONCLUSION: II is provocative of MS and postural instability.

Adult

Patent foramen ovale and hypobaric decompression.

Gas microbubbles were detected in the left ventricle of a supine subject being screened for an atrial septal defect as a participant of a hypobaric decompression study. This determination was made using the saline echocontrast procedure. We found provocation by a Valsalva maneuver not to be necessary in this individual for right-to-left passage of contrast microbubbles into the left heart and middle cerebral artery. When this same individual underwent hypobaric decompression to a simulated altitude of 21,000 ft, numerous gas microbubbles were detected in the right heart, but no gas bubbles were detected in either the left ventricular outflow tract or in the middle cerebral artery. This observation appears to be a novel finding, not previously reported.

Cerebral Arteries

Early stopping of aerospace medical trials: application of sequential principles.

A two-period, crossover trial was conducted in the hypobaric chamber on human subjects to compare the influence of inflight exercise (experimental) and restricted activity (control) on altitude decompression sickness (DCS) during simulated extravehicular activities. Out of 39 pairs (total of 78 exposures), 4 cases of DCS occurred under control and 5 occurred under experimental conditions. Analysis of the crossover results showed that the P values for differences in DCS occurrence was 0.56. Under these circumstances, it was necessary to decide whether additional information would be obtained by accruing more subjects. This problem was examined by using a skew sequential design in which the "stopping rule" was based on an alpha of 0.05 (one-sided) and power of 80%. The result of this analysis was in favor of the null hypothesis, and the trial was terminated. The authors recommend the use of similar stopping rules in aerospace trials to optimize sample size without compromising statistical validity.

Adult

Survivorship models for estimating the risk of decompression sickness.

Several approaches have been used for modeling the incidence of decompression sickness (DCS) such as Hill's dose-response and logistic regression. Most of these methods do not include the time-to-onset information in the model. Survival analysis (failure time analysis) is appropriate when the time to onset of an event is of interest. The applicability of survival analysis for modeling the risk of DCS is illustrated by using data obtained from hypobaric chamber exposures simulating extravehicular activities (n = 426). Univariate analysis of incidence-free survival proportions were obtained for Doppler-detectable circulating microbubbles (CMB), symptoms of DCS and test aborts. A log-linear failure time regression model with 360-min half-time tissue ratio (TR) as covariate was constructed, and estimated probabilities for various TR values were calculated. Further regression analysis by including CMB status in this model showed significant improvement (p < 0.05) in the estimation of DCS over the previous model. Since DCS is dependent on the exposure pressure as well as the duration of exposure, we recommend the use of survival analysis for modeling the risk of DCS.

Computer Simulation

Epidemiology of decompression sickness under simulated space extravehicular activities.

Several ground-based trials were conducted by NASA at the Lyndon B. Johnson Space Center, Houston, TX, during 1982-90 to examine the risk of altitude decompression sickness (DCS) during space extravehicular activities. There were 22 different pressure profiles involving single and staged decompression procedures, each lasting from 180 to 360 min at the final altitude. A total of 164 healthy subjects participated in 426 exposures to altitude. Symptoms of DCS occurred in 17% (74/426) and circulating microbubbles by precordial Doppler ultrasound were detected in 42% (179/426) of all exposures. About 27% (20/74) of exposures with symptoms resulted in test abort, and one-third of all test aborts required treatment in the hyperbaric chamber. There was about 3.20 times (95% Confidence Interval [95% CI] = 1.56-6.66) higher risk of symptoms in the presence of Doppler-detectable microbubbles. Examination of individual risk factors showed that there was about 4.3 times (95% CI = 1.62-11.50) higher risk of symptoms with increasing number of exposures. These findings emphasize the importance of evaluating risk factors from ground-based trials for application in operational decision-making and treatment strategies.

Adult

Preliminary report: modification of cardiac contraction rate by pulsed magnetic fields.

Isolated rat hearts and excised canine cardiac tissues were subjected to pulsed magnetic fields. The fields excited in coils by tandem pairings of sinusoidal pulses were presented at various inter-pair delays and repetition rates. The waveform of the magnetic field was a single or multiple sinusoid followed after a variable delay by another single or multiple sinusoid. Small but reliable increases in the beating rate of rat heart were observed. Similar increases occurred in contraction rates of canine tissues. Both preparations exhibited a contraction-rate dependency on the repetition rate of the paired magnetic pulses: 4.5-6 rep/s for canine tissue, and 20-25 and 40-55 reps/s for rat heart. Flux-density thresholds for both preparations approximated 10 mT (100 gauss) rms.

Animals

Time to detection of circulating microbubbles as a risk factor for symptoms of altitude decompression sickness.

This study investigated the association between time at onset of circulating microbubbles (CMB) and symptoms of altitude decompression sickness (DCS), using Cox proportional hazard regression models. The study population consisted of 125 individuals who participated in direct ascent, simulated extravehicular activities profiles. Using individual CMB status as a time-dependent variable, we found that the hazard for symptoms increased significantly (at the end of 180 min at altitude) in the presence of CMB (Hazard Ratio = 29.59; 95% confidence interval [95% CI] = 7.66-114.27), compared to no CMB. Further examination was conducted on the subgroup of individuals who developed microbubbles during the test (n = 49), by using Cox regression. Individuals with late onset of CMB (> 60 min at altitude) showed a significantly reduced risk of symptoms (hazard ratio = 0.92; 95% CI = 0.89-0.95), compared to those with early onset (< or = 60 min), while controlling for other risk factors. We conclude that time to detection of circulating microbubbles is an independent determinant of symptoms of DCS.

Adult

Trypanosoma cruzi: flow cytometric analysis of lymphocyte subsets in susceptible and protected C3H/He mice.

Inbred strains of mice vary widely in their ability to survive infection with Trypanosoma cruzi. C3H/He mice are highly susceptible to infection with the Brazil strain T. cruzi, but can be protected by immunization with avirulent Corpus Christi strain parasites. We have examined, during the course of infection, the changes in lymphocyte populations in C3H/He mice that were infected but protected by immunization, infected but not immunized, immunized but not infected, and normal age-matched controls. Immunization- and/or infection-induced changes in lymphocyte populations in lymph nodes were unremarkable except for an increase in the percentage of Ig+ cells. Conversely, in the spleen the percentages of mu+ cells decreased and T cells increased in all manipulated animals. The increase in splenic T cell subsets in immunized only controls occurred simultaneously and thus the CD4:CD8 ratio remained similar to that of normal animals (approximately 2.2). Twenty days after infection, mice that were infected but not immunized (and thus would be expected to die 4-8 days later) showed a dramatic increase in the percentage of CD8+ cells which resulted in a decline in the CD4:CD8 ratio to 0.85. Mice protected by immunization had a CD4:CD8 ratio of 1.7 at this critical time point, which did, however, decline to 1.0 by Day 60. The percentages of all cell phenotypes examined in all mice had returned to normal levels 155 days after infection. These data suggest that alterations in the splenic CD4:CD8 ratio may be important in determining whether or not an animal can survive infection with the Brazil strain of T. cruzi.

Animals

Carbohydrate epitopes are responsible for antibody cross-reactivity in Trypanosoma cruzi-infected mice.

Anti-Trypanosoma cruzi antibodies can be eluted from western blots of T. cruzi antigens and thereby are fractionated on the basis of the electrophoretic mobility of the antigens to which they bind. Antibodies fractionated by these methods can bind antigens with electrophoretic mobility different from those antigens from which they are eluted. Such antibodies thus are considered cross-reactive. Studies in which the target antigens are reacted with sodium periodate to destroy carbohydrate epitopes prior to exposure to the eluted antibodies revealed that antibodies are produced that bind to both carbohydrate and noncarbohydrate epitopes on western blots, but that most of the cross-reactive antibodies are directed toward carbohydrate moieties.

Animals

Analysis of antibody cross-reactivity in experimental American trypanosomiasis.

Susceptible C3H/He mice were immunized with the avirulent Corpus Christi strain of Trypanosoma cruzi and subsequently infected with virulent Brazil stain organisms. Seventy days after infection sera were isolated and analyzed on western blots of electrophoretically separated T. cruzi antigens prepared from culture-form parasites (primarily epimastigotes). More than 25 bands were identified. The antibodies were fractionated by elution from various regions of western blots corresponding to average molecular weights of approximately greater than 130, 77, 70, 60, 48, or 38 kDa. Each of these antibody preparations was then incubated with strips of nitrocellulose containing all of the electrophoretically separated T. cruzi, and cross-reactivity was determined. Antibodies isolated from the 130-, 77-, and 70-kDa regions all cross-reacted with each other. Antibodies eluted from the 60-kDa region bound antigens in the 60-, 70-, and the 77-kDa regions. More importantly, antibodies eluted from every region bound antigens in the 70-kDa region. Conversely, antibodies eluted from this region bound to antigens in all of the other regions. These data indicate the presence of (a) common antigenic epitope(s) in T. cruzi infections in these mice that is predominantly found in the 70-kDa antigen-antibody complex on western blots.

Animals

Low-level, magnetic-field-induced growth modification of Bacillus subtilis.

Experimental studies showed an increase in the growth of Bacillus subtilis mutant strain FJ7 above controls by exposing the bacterial culture to 800-Hz or 1-KHz magnetic fields with a 2-s-on/2-s-off period. The magnetic field strength was between 0.8 and 2.5 mT. Light microscopy and scanning electron microscopy demonstrated the morphology of controls to grow in a macrofiber of right-handed helix formation. In contrast, the field-exposed group showed little to no cohesion; the cells appeared to be homogeneously distributed throughout the sample. These results suggest that growth patterns of Bacillus subtilis can be altered as a result of magnetic-field-induced effects.

Bacillus subtilis

Anti-idiotypic T lymphocyte responsiveness in murine Schistosomiasis mansoni.

Pooled sera from CBA/J mice infected for greater than or equal to 16 weeks with the blood fluke Schistosoma mansoni were immunoaffinity purified using soluble schistosome egg antigens (SEA) coupled to Sepharose 4B. The bound and then eluted fraction was shown to contain only immunoglobulins and to have anti-SEA activity. These anti-SEA antibodies stimulated proliferation of lymph node cells from mice infected with S. mansoni for 8, 12, or greater than or equal to 16 weeks but not from uninfected mice. The cells stimulated by anti-SEA antibodies were nylon wool adherent, Thy-1.2+, L3T4+, Lyt-2-lymphocytes. Immunoglobulins without anti-SEA activity isolated from the sera of syngeneic uninfected mice were not stimulatory for cells from normal or infected animals. Thus the responding T cells appear to be stimulated by the idiotypes expressed on the syngenic anti-SEA antibodies. These data present evidence for anti-idiotypic cellular reactions in murine schistosomiasis that could play important immunoregulatory roles in this disease.

Animals

Increased vertebral bone mineral in response to reduced exercise in amenorrheic runners.

Seven female runners found to have exercise-induced amenorrhea and decreased bone mineral were reevaluated after 15 months. During the 15-month period, four runners took supplemental calcium and reduced their weekly running distance by 43%, resulting in an average 5% increase in body weight, increased estradiol levels and eumenorrhea. Bone mineral content increased from 1.003+/-0.097 to 1.070+/-0.089 grams per cm.(2) Three runners continued to have amenorrhea, with no change in running distance or body weight. Estradiol levels remained abnormally low and there was no significant change in the bone mineral content, although all three took supplemental calcium. We found that early osteopenia associated with exercise-induced menstrual dysfunction improved when runners reduced their running distance, gained weight and became eumenorrheic.

Adult

Demonstration of splenic auto-anti-idiotypic plaque-forming cells in mice infected with Schistosoma mansoni.

Mice exposed to 35 cercariae of the human helminth Schistosoma mansoni develop chronic (greater than 16wk) infections characterized by immunoregulation of their cell-mediated granulomatous responses to schistosome eggs. Evidence was sought regarding the possible development of anti-idiotypic responses against the responses to soluble egg antigens (SEA). Sera were collected from CBA/J mice with chronic S. mansoni infections. Multiclonal idiotypic, anti-SEA antibody (id) was prepared from these pooled sera by affinity chromatography on an SEA immunoadsorbent column. Analysis of the id preparations by polyacrylamide gel electrophoresis demonstrated that this material contained only immunoglobulin heavy and light chains. A modified reverse plaque-forming cell (PFC) assay was developed to quantify anti-idiotypic (anti-id) PFC in spleen cell preparations from infected and age-matched control CBA/J mice. Expression of anti-id PFC began 2 to 3 wk after onset of egg production and continued throughout the course of infection. Positive selection of anti-id-reactive spleen cells by panning cell preparations from chronic mice on id-coated plates resulted in an enrichment of anti-id PFC in the id-adherent population. Conversely, the number of PFC reactive with SEA (id-producing PFC) was lowered by panning on id-coated plates. These data demonstrate the occurrence of anti-id responses during schistosomiasis mansoni. It is possible that such an immunoregulatory mechanism could play an important role in how an animal modulates the granulomatous response that leads to the formation of pathologic lesions and in the maintenance of this chronic infection.

Animals