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Biomedical subjects

R J Brooks

Publications and source records attributed to R J Brooks.

18 recordsLinked to original sources

The case for a cause-effect linkage between environmental contamination and development in eggs of the common snapping turtle (Chelydra S.serpentina) from Ontario, Canada.

Concentrations of polychlorinated biphenyls (PCBs), dibenzo-p-dioxins, and dibenzofurans, organochlorine pesticides, and their metabolites were measured in eggs of the common snapping turtle (Chelydra s.serpentina) collected from four wetlands on the shorelines of Lakes Ontario, and Erie, and one control location in central Ontario, Canada. Snapping turtle eggs from these sites were also artificially incubated to determine hatching success, and incidence of deformities in embryo and hatchling turtles. The hypothesis that elevated incidences of egg death and/or deformities of hatchling turtles would occur in populations with high concentrations of organochlorine contaminants in eggs was tested. The results were elevated using epidemiological criteria. Unhatched eggs and deformities occurred at significantly higher rates in eggs from Lake Ontario wetlands. Two of three sites from Lake Ontario had substantially higher levels of PCBs, dioxins, and furans compared to eggs from Lake Erie and the control site. It could not be shown that contamination of eggs preceded the occurrence of poor development of eggs, although excellent hatching success and low numbers of deformities in eggs from the control site were considered representative of development in healthy eggs. The statistical association between contaminant levels in eggs and poor development of these eggs supported the hypothesis that eggs from sites with the greatest contamination had the highest rates of abnormalities. PCBs were the most strongly associated chemicals, although possible effects due to the presence of other chemicals in eggs was a confounding factor. The deformities and rates of unhatched eggs were similar to those occurring in other vertebrates collected from highly contaminated areas of the Great Lakes. There were several chemicals present in the eggs that can cause similar reproductive effects in other species; therefore a specific chemical effect was not identified. Results were coherent with known statistical and biological information. Theoretical and factual evidence of PCB contamination in wild-caught snapping turtles supported and hypothesis. However, lack of controlled studies of reproductive effects of polychlorinated hydrocarbons upon this species hindered the agreement of all factual and theoretical evidence with the hypothesis.

Animals

Modelling sub-binomial variation in the frequency of sex combinations in litters of pigs.

In some samples of pig litters, the number of males per litter exhibits significant sub-binomial dispersion: there are fewer unisexual and more "sex-balanced" litters than expected under a binomial model. It is argued here that the explanation is that the sex of zygotes may be subject to hormonal control with the consequence that, within a litter, the zygotes do not all have the same probability of being male. This variation in probability is approximated by a quadratic function of the time during oestrus that a zygote is formed so as to parallel the variation in maternal hormone levels. Other explanations are examined briefly, but each seems to have serious weaknesses.

Analysis of Variance

Ultrastructural development of the sarcocyst of Sarcocystis rauschorum (Apicomplexa: Sarcocystidae) in the varying lemming Dicrostonyx richardsoni.

The development of the sarcocyst of Sarcocystis rauschorum in its intermediate host was studied. Lemmings were orally administered sporocysts of S. rauschorum obtained from snowy owls (Nyctea scandiaca). Beginning at 9 days postinoculation (DPI) and at various intervals to 84 DPI, skeletal muscle tissue taken from the infected lemmings was examined by electron microscopy. At 9 DPI the sarcocysts contained few metrocytes and the cyst wall was flat. The metrocytes underwent endodyogeny, and within a few days the cyst wall of the rapidly growing sarcocyst developed numerous tubulovesicular invaginations into the electron-dense layer, and the wall had a few irregular infoldings. By 21 DPI, banana-shaped bradyzoites appeared, and by 84 DPI the mature cysts were filled with bradyzoites in groups subdivided by septa and by deep infoldings of the cyst wall. The fine structure of the wall remained simple throughout maturation, with no conspicuous invagination or protrusion. The sarcocyst produced in response to S. rauschorum is unlike those from many species of Sarcocystis, which have complex walls that change markedly as the sarcocysts mature; however, its simple appearance is similar to other species that have rodents as intermediate hosts and raptorial birds as definitive hosts.

Animals

Hatchling turtles survive freezing during winter hibernation.

Hatchlings of the painted turtle (Chrysemys picta marginata) are unique as the only reptile and highest vertebrate life form known to tolerate the natural freezing of extracellular body fluids during winter hibernation. Turtles survived frequent exposures to temperatures as low as -6 degrees C to -8 degrees C in their shallow terrestrial nests over the 1987-1988 winter. Hatchlings collected in April 1988 had a mean supercooling point of -3.28 +/- 0.24 degrees C and survived 24 hr of freezing at -4 degrees C with 53.4% +/- 1.98% of total body water as ice. Recovery appeared complete after 20 hr of thawing at 3 degrees C. However, freezing at -10.9 degrees C, resulting in 67% ice, was lethal. A survey of possible cryoprotectants revealed a 2- to 3-fold increase in glucose content of liver and blood and a 3-fold increase in blood glycerol in response to freezing. Although quantitatively low, these responses by spring turtles strongly indicate that these may be the winter-active cryoprotectants. The total amino acid pool of blood also increased 2.25-fold in freezing-exposed turtles, and taurine accounted for 52% of the increase. Most organs accumulated high concentrations of lactate during freezing, a response to the ischemic state imposed by extracellular freezing. Changes in glycogen phosphorylase activity and levels of glucose 6-phosphate and fructose 2,6-bisphosphate were also consistent with a dependence on anaerobic glycolysis during freezing. Studies of the molecular mechanisms of natural freeze tolerance in these turtles may identify protective strategies that can be used in mammalian organ cryopreservation technology.

Animals

Neurobehavioral and psychosocial functioning of women exposed to high altitude in mountaineering.

The effects of chronic hypoxemia upon cognition and behavior were studied in women exposed to high altitude in mountaineering. Neuropsychological tests and psychosocial and physiological questionnaires were given to eight women before, during, and immediately after a Himalayan climb to 20,500 feet. Cognitive functioning remained relatively intact with only two significant decrements, complex abstract reasoning and word-finding ability. Significant changes were found on all psychosocial and physiological questionnaires. Feelings of acceptance of others and anxiety declined significantly. Physical symptoms were greatest during the first five days of ascent. Subjects' self-ratings of mental functioning were significantly better after the expedition than either before or during the climb. Self-assessments were correlated with emotions and physical symptoms, not with actual performances on the test battery. It is suggested that complex cognitive tasks and psychosocial functioning be studied in more detail as these were more influenced by exposure to high altitude in mountaineering.

Adult

Cholesterol hydroperoxides inhibit calmodulin and suppress atherogenesis in rabbits.

A mixture of cholesterol autoxidation products, prepared from an aged sample of cholesterol by recrystallization from methanol, inhibits calmodulin irreversibly in a Ca2+-dependent reaction. Inhibitory activity is lost after treatment with NaBH4, NaCNBH3, or NaI, from which we conclude that calmodulin inhibition is due to one or more cholesterol hydroperoxides. Partially purified cholesterol hydroperoxides, with or without cholesterol, were fed to young adult white rabbits. Cholesterol in the diet caused extensive atheroma formation in the aortas, but the addition of cholesterol hydroperoxides markedly reduced lesion formation. A cholesterol hydroperoxide preparation that was reduced by treatment with NaI was not effective in preventing atheroma formation. Cholesterol hydroperoxides did not lower cholesterol concentrations in blood plasma, liver, or heart.

Aging

Pathogenesis of infection with Sarcocystis rauschorum (Apicomplexa) in experimentally infected varying lemmings (Dicrostonyx richardsoni).

This study describes the sequential formation of lesions associated with the endogenous development of Sarcocystis rauschorum (Apicomplexa: Sarcocystidae) in varying lemmings, Dicrostonyx richardsoni. Lethal doses of sporocysts (greater than 500) were orally administered to lemmings examined 1-6 days postinoculation (DPI) whereas sublethal doses were administered to lemmings examined subsequently. Transient necrosis and purulent inflammation, in association with precystic merogony, occurred in the liver by 4.5 DPI, peaked at 6 DPI and subsided beginning at 11 DPI with the liver returning to normal by 15 DPI. Cyst formation in skeletal and cardiac muscle was associated with purulent inflammation and sarcolemmal proliferation beginning at 9 DPI. These lesions persisted to 42 DPI. In addition, multifocal nonsuppurative meningoencephalitis was present in six of 11 infected lemmings examined between 11 and 15 DPI.

Animals

Effects of the protozoan parasite Sarcocystis rauschorum on open-field behaviour of its intermediate vertebrate host, Dicrostonyx richardsoni.

Behaviour and activity levels were measured in varying lemmings experimentally infected with the heteroxenous parasite, Sarcocystis rauschorum to test the hypothesis that the parasite alters behaviour of this intermediate host and thereby increases probability of transmission to the definitive host, the snowy owl (Nyctea scandiaca). Measures of short-term activity levels on a running wheel indicated no effect of the parasite, either directly, or indirectly as a result of illness. We observed behaviour of infected lemmings placed in an "open field" (arena). Lemmings would increase their susceptibility to predators if they spent more time away from cover, used crypsis (stationary postures) less, spent more time exploring (especially in unfamiliar areas), or responded inappropriately to threats from predators. We found that only exploratory activity showed significant change after infection. The frequency of exploratory activity increased and became disassociated from the usual fear response. This may increase the lemmings' susceptibility to aerial predation. The mechanism for this effect is unknown, but neurological lesions have been observed. The examination of the modes of transmission of the S. rauschorum parasite within lemming populations and of a possible fecundity compensation strategy adopted by the lemmings, and their relevance to population control, are suggested as areas for future study.

Animals

Adjuvant chemotherapy of axillary node-negative carcinoma of the breast using doxorubicin and cyclophosphamide.

One hundred fifty-six women with axillary node-negative breast cancer and primary tumors less than or equal to 5 cm in diameter (T1N0 or T2N0) were treated with a brief course of postoperative adjuvant chemotherapy consisting of doxorubicin and cyclophosphamide. Treatment was well tolerated and toxicity was minimal. With a median follow-up time of 58 months, there has been 1 relapse among 58 patients with T1 primary lesions and 15 relapses among 98 patients with T2 primary tumors. When compared with a matched historical control group receiving surgery alone, significant improvement was apparent in disease-free survival among the patients who received adjuvant chemotherapy. Prospective controlled trials are needed if we are to confirm this favorable experience with adjuvant chemotherapy in the treatment of women with node-negative breast cancer.

Adult

Failure of strange females to cause pregnancy block in collared lemmings, Dicrostonyx groenlandicus.

The effects of exposure to unfamiliar females on pregnancy success of recently mated females were examined in collared lemmings (Dicrostonyx groenlandicus). Four days after mating, females in their home cage were exposed to strange, female intruders that were either nonpregnant or 16 days pregnant. Other recently mated females were introduced to the home cage of 16-day-pregnant females. Pregnancy success of the recently mated females was not reduced in any of these treatments. In the paired encounters, there was no relationship between dominance status and pregnancy status, nor between dominance and pregnancy success. These results do not support the hypothesis that in species in which females are aggressive and readily commit infanticide, unfamiliar females should cause other females to terminate early-stage pregnancies.

Abortion, Spontaneous

Treatment of advanced breast cancer with mitomycin C combined with vinblastine or vindesine.

Mitomycin C together with either vindesine or vinblastine was given to 48 patients with previously treated advanced breast cancer. Thirteen (35%) of the 37 evaluable patients had a complete (one patient) or partial (12 patients) response. Overall median duration of response was 189 days (range, 90-700 days). Fifteen patients received mitomycin C and vindesine with six responses (40%) and a median response duration of 247 days (range, 162-700 days). Twenty-two patients received mitomycin C and vinblastine with seven responses (32%) and median response duration of 164 days (range, 90-330 days). Response duration for patients treated with mitomycin C plus vindesine was longer than that associated with mitomycin C plus vinblastine (p = 0.09). Significant toxicity included myelosuppression and neurologic symptoms, but was uncommon (less than 10% of patients). Therefore, the combination of mitomycin C and a vinca alkaloid appears to be useful in far-advanced refractory breast cancer.

Adult