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Biomedical subjects

D B Wilson

Publications and source records attributed to D B Wilson.

At least 289 records · Page 16Linked to original sources

Studies of the MHC-linked "CT" alloantigenic system in rats. II. Evidence for more than one locus and several different determinants.

Previous studies have defined a novel, MHC-linked alloantigenic system in the rat (CT) detectable with cytotoxic T cells (CTL) generated by alloimmunization and restimulation using strain combinations thought to be RT1-compatible, for instance, Lewis and Fischer 344. CTLs generated in this way are able to lyse targets from a variety of different strains without any evidence of MHC-restricted interactions, and yet these CT determinants possess properties unlike conventional class I and class II MHC gene products. The present studies employ cold target competition assays to derive a minimal estimate of the number of different CT determinants detected with Lewis anti-Fischer 344 CTLs, the number of loci involved in their expression, and their strain distribution. The results indicate that Lewis anti-Fischer CTLs define at least four different determinants encoded by at least two different loci.

Animals↗

Fine structure of somatotrophs and mammotrophs in the pituitary pars distalis of the little (lit) mutant mouse.

The cellular pathology and postnatal differentiation of somatotrophs and mammotrophs in the pars distalis of little (lit/lit) and normal (+/+; lit/+) mice were studied by means of electron microscopy. The results indicate that in little the pituitary at birth contains recognizable somatotrophs and mammotrophs; however, between 14 and 24 days of age a contrast between little and normal becomes conspicuous with respect to the somatotrophs. Little somatotrophs are less heavily populated with granules, have granules of smaller size, and show less developed organelles than do normal somatotrophs at comparable stages. Beyond 24 days the little somatotrophs become more difficult to locate, and those that do occur show a minimal increase in complexity from that present at 14 days. In contrast, the mammotrophs in little are similar in appearance to normal mammotrophs and show increasing complexity as development proceeds, often sending forth cellular processes between neighboring cells, as do normal mammotrophs.

Animals↗

The cell cycle during closure of the neural folds in the C57BL mouse.

An analysis of cellular kinetics during closure of the cranial neural folds in the C57BL mouse at 8 and 9 days gestations was obtained by means of tritiated thymidine autoradiography. At 8 days the short generation time (7.5 h) and high labeling index (61.4%) are evidence of intensive proliferative activity occurring concurrently with significant changes in cell shape and movement during neural fold elevation and approximation.

Animals↗

Incorporation of tritiated thymidine in the hypophysis of the rhesus monkey (Macaca mulatta) embryo.

Proliferation and growth in the neurohypophysis and adenohypophysis, including the pars distalis, pars intermedia and pars tuberalis, were studied in a series of rhesus monkey embryos of stages 13 to 21 (from 26 to 41 days of gestation) and labelled for one hour with a single intrachorionic injection of 3H-thymidine. As early as stage 13 the anlage of the neurohypophysis is foreshadowed in the floor of the diencephalon by a relatively low level of proliferation, with a labelling index (LI) of 35.1% as compared with an LI of 66.7% in the lateral walls of the diencephalon and an LI of 59.5% in the hypophyseal pouch. By stage 16 the neurohypophyseal anlage consists of a well-defined infundibulum, most of whose cells are unlabelled, (LI = 2.8%), in contrast with the more heavily labelled hypophyseal pouch (lateral walls = 45.3%; dorsal wall = 40.3%; ventral wall = 41.0%). The wall of the anlage of the adenohypophysis is in close apposition with the wall of the neurohypophysis until stage 21 when mesenchymal cells can be seen penetrating between the two. Near the communication of the hypophyseal pouch with the stomodeum the ventral walls of the hypophyseal pouch show a drastic reduction in labelling (LI = 8.0%) at stage 16. Although the pouch loses its contact with the stomodeum at stage 18, well-defined remnants of its earlier connection can still be seen as an irregular strand of cells at stage 21.

Animals↗

Fine structure of somatotrophs and mammotrophs during development of the dwarf (dw) mutant mouse.

The differentiation of somatotrophs and mammotrophs in the pars distalis of dwarf (dw/dw) and normal (+/+; dw/+) litter mates was studied by means of electron microscopy from the day of birth to 24 days, as well as in adults at 3-4 months of age. On the basis of a combination of growth measurements, including weight, total body length, and tail length, dwarfs were identifiable with certainty as early as 5 days in litters from heterozygous matings (dw/+ x dw/+). Newborn dwarfs were obtained from homozygous matings (dw/dw x dw/dw) of adult dwarfs which had been brought to sexual maturity by hormone supplementation. The results indicate that the dwarf pituitary is already abnormal at birth. In contrast to the pars distalis in the normal newborn mouse, somatotrophs and mammotrophs cannot be distinguished from one another nor can they be distinguished as a group from other cell types in the dwarf. However, as development progresses, the dwarfs show a large population of an ambiguous somatotroph-mammotroph-like cell with fine structural characteristics of both somatotrophs and mammotrophs; these ambiguous cells also occur in the 3-4 months old adult.

Aging↗

Cellular proliferation in the exencephalic brain of the mouse embryo.

Autoradiographic studies were conducted on the midbrain and cerebral hemispheres of abnormal (Lp/Lp) exencephalic embryos and normal littermates at 12--18 days of gestation. At 12 days of gestation the percentage of cells labeled (labeling index, LI) in the abnormal brains was similar to that in the normals; however, by 14 and 16 days, the LI had decreased in the normal brains but remained the same in the abnormals. Although an accurate labeling index could not be determined in the 18-day abnormals because of the necrosis and severe histological distortion, incorporation of tritiated thymidine continued to occur, but at an apparently reduced level from earlier stages. On the basis of differences in the LI at 14--16 days of gestation, it appears that cells in the abnormal brains retain their ability to proliferate for longer periods of development than is the case in normal brains.

Animals↗

Monoclonal rat anti-major histocompatibility complex antibodies display specificity for rat, mouse, and human target cells.

24 monoclonal rat antibodies are described that are reactive with determinants encoded by the major histocompatibility complex (MHC) of the rat. These hybridoma antibodies were derived by fusing mutant mouse myeloma cells to spleen cells from Lewis rats immunized with allogeneic Brown Norway cells. All 24 antibodies are cytotoxic for both Brown Norway target cells and target cells from the appropriate MHC congenic rats. Pattern of cytotoxicity and hemagglutination strongly suggest reactivity against class I (K or D equivalent) rat MHC determinants. Cytotoxic cross-reactivity patterns were generated for each monoclonal antibody on a panel of rat and mouse lymphoid cells and human peripheral T lymphocytes. A high degree of interspecies cross-reactivity was noted with approximately one-half of the antibodies positive on human and/or mouse target cells. 11 antibodies recognized polymorphic determinants in the mouse, and, by using target cells from MHC congenic mouse strains, it was shown that these determinants are encoded by genes within the H-2 complex. Finally, by considering the overall reactivity patterns of these monclonal antibodies on all target cells, one can show that these 24 antibodies represent a minimum of 14 antibody specificities.

Animals↗

Early development of the brain and spinal cord in dysraphic mice: a transmission electron microscopic study.

The hindbrain and spinal cord were studied by transmission electron microscopy with and without lanthanum nitrate treatment in nine-day embryos of the loop-tail (Lp) mutant mouse. Homozygous (Lp/Lp) individuals exhibit dysraphism from the hindbrain caudally throughout the embryo; in +/+ and Lp/+ individuals, the brains and spinal cords are normal. In contrast, the ventricular cells in the abnormal hindbrain and spinal cord showed increased amounts of intercellular space in an area intermediate between the luminal border and basal zone, and a flattening which occurs variably in their luminal surfaces. A most striking difference occurred in the frequency of gap junctional vesicles, circular structures bounded by a double membrane and containing ribosome-like material. A quantitative analysis of the distribution of these organelles revealed that they are more numerous in the dysraphic hindbrain and lumbosacral spinal cord of the abnormal animals than in comparable regions of the normal; however, in the cervicothoracic spinal cord, the frequency of these vesicles is similar. In specimens treated with lanthanum, the tracer freely penetrated the luminal junctional complexes in both normal and abnormal animals, but was not present between the membranes of the gap junctional vesicles. The developmental significance of gap junctional vesicles frequently located in juxtaluminal regions of mitotic cells, but also found deeply in dividing cells, is not known; they may relate to cell-to-cell attachment and/or communication. In any event, further study of them may prove valuable in understanding normal and abnormal development of the neural tube.

Animals↗

Postnatal development of somatotrophs and mammotrophs in the pars distalis of the C57BL mouse.

The pars distalis of the pituitary gland of the C57BL mouse was studied by means of electron microscopy during postnatal stages of males ranging in age from newborn through 24 days, with particular emphasis on the somatotrophs and mammotrophs. During this period, growth curves were plotted in order to correlate postnatal growth patterns with the state of differentiation of the somatotrophs in the pars distalis. In the newborn, the somatotrophs show well developed organelles, including rough endoplasmic reticulum and Golgi complexes. These cells are not as densely packed with granules as the adult somatotrophs; however, from days 5 through 24, they show a progressive accumulation of granules. Although mammotrophs are scarce in the newborn, they are readily distinguishable in the pars distalis at 5 days. Male mice in small litters show a progressive increase in body weight between birth and 11-12 days, at which time the rate slackens until 18-19 days when the rate again increases. Growth curves for mice from large litters are similar to those from smaller litters, except that the transitory decrease in rate is more prominent.

Animals↗

Changes in serum enzyme levels following ketamine infusions.

The levels of four serum enzymes, known to be elevated in toxic hepatitis, were measured preoperatively and on the 3-4th and 13-15th postoperative days in patients anaesthetised with ketamine infusions (54) or with a standard technique (64). Significant elevations in enzyme levels were considered to have occurred when the postoperative levels were outside the accepted normal range and had increased by more than 3 X SD from controls. About half the patients in each group had minor gynaecological operations and 2/20 in the ketamine series had postoperative elevation of enzyme levels, with no changes in the non-ketamine group. Following intermediate operations 14/34 anaesthetised with ketamine showed abnormal enzyme levels compared with 7/34 who had standard operations. None of the latter had more than one abnormal test as compared with six in the ketamine series. The causes and significance of these findings are not known.

Adult↗

Amnesic action of midazolam.

Midazolam 5 mg, a water-soluble benzidiazepine, given intravenously to adults had a maximum effect of impairing memory for postcards shown between 2 and 5 min after injection. This effect has mainly passed off in 20 min.

Adult↗