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Biomedical subjects

D S Mitchell

Publications and source records attributed to D S Mitchell.

At least 19 recordsLinked to original sources

Single nucleotide polymorphism in prohibitin 3' untranslated region and breast-cancer susceptibility.

The RNA encoded by the 3' untranslated region of the prohibitin gene arrests cell proliferation by blocking the transition between the G1 and S phases of the cell cycle. The product of a variant allele (T allele) is inactive. We did a case-control study of prohibitin genotype in 205 women with breast cancer and 1046 healthy controls. The results showed an association between the T allele and breast cancer in women who reported a first-degree relative with the disease (odds ratio 2.5, p=0.005). An even stronger association was found in a subset of women diagnosed at or before age 50 years (4.8, p=0.003). These data suggest that prohibitin genotyping has value in assessing risk of breast cancer in women aged 50 years or younger with at least one first-degree relative with the disease.

Adult↗

Case report of a newborn with a posterior thoracic midline congenital hemangiopericytoma of the back.

The posterior thoracic midline location is an unusual site for a congenital hemangiopericytoma. The authors report such a case that caused near fatal exsanguination of a newborn after vaginal delivery. Magnetic resonance imaging (MRI) studies of the mass were completed after hemostasis. These studies showed a well-defined border between the tumor and underlying trapezius muscle. The mass was removed successfully surgically and presumed initially to be a teratoma. Pathological diagnosis of the tumor was hemangiopericytoma with low malignant potential. After a 9-day hospital course, the patient was discharged with recovering hepatic and renal function.

Back↗

PET hydroxyephedrine imaging of neuroblastoma.

UNLABELLED: The goals of this investigation were to characterize the uptake of 11C-hydroxyephedrine (HED) in neuroblastoma and to determine the feasibility and potential advantages of utilizing this compound as a tumor imaging agent. METHODS: Seven patients with known or subsequently proven neuroblastoma were studied. Each patient underwent PET scanning with 11C-HED. Six of seven patients underwent scintigraphy with [123I]meta-iodobenzylguanidine (MIBG), and two patients were also studied with [18F]FDG PET. For six patients, CT or MR images were available for comparison. RESULTS: Neuroblastomas were located by PET scanning with 11C-HED in all seven patients. The uptake of HED into neuroblastomas was rapid; tumors were evident on images within 5 min postintravenous injection. Those lesions in the field of view of the PET camera were also identified on [123I]MIBG scintigraphic images. In two patients, tumor deposits in the abdomen were better visualized with MIBG scintigraphy due to relatively less hepatic accumulation of MIBG than HED. CONCLUSION: PET scanning with HED for neuroblastoma results in high quality functional images of the tumors that can be obtained within minutes following injection.

3-Iodobenzylguanidine↗

Neoplasms in a pediatric population: 2-[F-18]-fluoro-2-deoxy-D-glucose PET studies.

PURPOSE: To assess the uptake of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) in common and uncommon tumors in children and to develop a method for performing positron emission tomography (PET) studies in children with malignant neoplasms. MATERIALS AND METHODS: Twenty-two pediatric patients with known or suspected malignancies (27 scans) underwent FDG PET. Tumor uptake of FDG was measured on PET scans. RESULTS: Tumor uptake of FDG was detected in 17 of 21 patients with malignant disease. Neuroblastomas and their metastases (including those that did not absorb metaiodobenzylguanidine) intensely accumulated FDG. In a patient with Ewing sarcoma, FDG PET showed two foci of metastatic disease not evident on bone scans. In two patients, PET showed that large areas of the tumor were necrotic. CONCLUSION: FDG PET is feasible, is useful in the study of tumors in children, and may provide unique, clinically important information.

Adolescent↗

SAS, a gene amplified in human sarcomas, encodes a new member of the transmembrane 4 superfamily of proteins.

Amplification of 12q13-14 occurs in a subset of human sarcomas including malignant fibrous histiocytoma and liposarcoma. This chromosomal region has previously been found to include a number of growth-related genes including the GLI proto-oncogene and the p53-associated protein, MDM2. We now report the characterization of SAS (sarcoma amplified sequence), a novel transcript found in this region. Sequence analysis demonstrates that SAS is a novel member of a transmembrane protein family (transmembrane 4 superfamily or TM4SF) thought to be involved in growth-related cellular processes. This observation adds a TM4SF protein to the cluster of genes at 12q13-14 frequently amplified in human sarcomas.

Amino Acid Sequence↗

Salt taste preference in baboons.

Dietary salt (NaCl) has been implicated in the etiology of hypertension and atherosclerosis, although its role remains controversial. The human preference for salted foods is well-known and many investigators believe the taste for salt is acquired. An experiment we conducted suggests that the baboon does not have an acquired taste for salt. A sample of 36 baboons from a population of 70 baboons of known sire, sex, and dietary history was used; each had been raised since birth on a diet of fixed salt content in a study of dietary salt and blood pressure. Given this unique group of animals, we decided to test whether baboons raised on one dietary salt level (low, medium, or high) would prefer a different level. After baseline consumption was measured for 9 days, we offered each animal equal amounts of all 3 diets simultaneously in a counterbalanced randomized sequence for 9 days, controlling for tray position preference and color preference. We measured consumption of each diet by weighing the amount of food remaining. Our statistical analyses indicated an overwhelming preference for the lowest dietary salt level, regardless of which diet the animal had been fed since birth (p less than 0.0001).

Animals↗

Ia-positive macrophages bind and internalize viable lymphocytes in murine thymus.

Macrophages have been shown to be present in thymus throughout its development. In the present study monoclonal and polyclonal antimacrophage reagents were used to identify, quantitate, and determine the distribution of thymic macrophages. Those studies demonstrated that significant numbers of macrophages were evenly distributed throughout the cortex and medulla, and that macrophages account for most, if not all, Ia positivity in murine thymus. Suspensions of thymic cells prepared by enzyme digestion contained 2-4% macrophage antigen-positive cells, over 95% of which were I-Ak positive in double-labeling studies. Removal of lymphocytes and macrophages left only epithelial cells and those failed to label for Ia. Subsequent to mild enzymatic digestion, up to 80% of the thymic macrophages were in the form of lymphocyte/macrophage rosettes. Morphologic evaluation of the thymocyte rosettes revealed that some of the macrophages contained internalized lymphocytes. The proportion of macrophages with internalized lymphocytes generally was less than 10%, but during the first 4 weeks of life values often approached 30%. Nurse cells, which were shown through double labeling to express both Ia and macrophage-associated antigen, were included in the population of rosetted cells which had internalized lymphocytes. The results demonstrated that there is a high level of interaction between lymphocytes and Ia-positive macrophages in the thymus which is greatest during the immediate postnatal period.

Age Factors↗

Estrus-related odors in body fluids of dairy cows.

Six experiments were to test for estrus-associated odors in 1) swabs of the vulva and vestibule, 2) fluids from deep in the vagina, 3) naturally voided urine, 4) urine obtained from the bladder by catheter, 5) milk, and 6) blood plasma. Tests were with dogs trained to identify vaginal fluids from estrous cows. In the tests, dogs were walked along lines of seven sample bottles consisting of samples from two estrous cows, two luteal-phase cows, one vaginal swab from estrous cows used as a standard, and two blank sample bottles. Correct responses to fluids from estrous cows averaged 97, 86, 96, 97, 99, and 94% for the six fluids listed. Incorrect responses to fluids from luteal-phase cows were 2, 1, 1, 1, 1, and 8%. Responses to blank samples were usually zero. Results indicate that odors associated with estrus are spread throughout the cow's body fluid.

Animals↗

Flavor preferences, food intake, and weight gain in baboons (Papio sp.).

To evaluate the influence of flavor on ad lib consumption and on associated changes in body weight, female baboons, 7-15 years of age, served in two experiments with seven monkey chows which were identical except for flavor: lemon, orange, apple, sugar, fruit punch, chocolate, and unflavored. In the first experiment, two groups of animals (n=7 and 4) received five of the seven flavors, presented in daily pair-wise combinations. Analysis of quantities consumed demonstrated marked and consistent flavor preferences in individual baboons. Although specific preference varied between animals, total amounts consumed of the various flavors differed significantly, with rank ordering clearly evident. Overall food intake and body weights increased significantly over baseline values obtained with a standard, unflavored chow. In the second experiment, three baboons received chow of a preferred flavor for nine weeks. Amounts consumed and body weights increased significantly over baseline. These results indicate that flavored chows may be useful for producing a nonhuman primate behavioral model of obesity and for inducing animals to eat otherwise unpalatable diets.

Animals↗

Estrus-related odors in cows: time of occurrence.

One Catahoula Leopard Cowdog and three German Shepherd dogs, previously trained to detect odors characteristic of estrus in cows, were used in three experiments to determine when estrus-related odor first appears, how long it persists, and when it disappears in relation to time of estrus. Samples were swabs of reproductive tract fluids taken from vaginas of cycling cows on the day of estrus, at diestrus (8 to 10 days after estrus), and at daily intervals before and after estrus. Estrous odor emerges slowly during the 3 days before estrus, reaches a definite peak in intensity on the day of estrus, and disappears within 1 day thereafter.

Animals↗

Noninvasive oscillometric measurement of blood pressure in baboons (Papio cynocephalus).

The accuracy and reliability of noninvasive measurement of blood pressure in the forearms of baboons by means of an automated oscillometric method were evaluated. Comparisons of 255 oscillometric determinations of systolic, diastolic and mean arterial pressure in eight anesthetized animals with simultaneously taken direct radial artery pressure measurements revealed average differences and standard deviations of +0.14 (+/- 9.05), +4.34 (+/- 6.75), and -1.01 (+/- 5.84) Torr, respectively. Computation of statistical error bounds indicated that any single oscillometric reading could be expected to fall within 9.6%, 11.0% nd 7.4% of directly measured systolic, diastolic, and mean blood pressure with a probability of 0.90. The oscillometric determinations accurately tracked rapid changes in pressure caused by intravenous infusion of pressor and depressor drugs. The method provided fast, reliable readings of arterial pressure without the use of microphones or other transducers that require precise placement and low-noise environments.

Animals↗