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Biomedical subjects

K A Stevens

Publications and source records attributed to K A Stevens.

At least 19 recordsLinked to original sources
PubMed1996

Mice deficient for the amyloid precursor protein gene.

To understand the in vivo function of the amyloid precursor protein (APP) we generated an APP null mutation in mice by homologous recombination in embryonic stem (ES) cells. We show here that homozygous APP deficient mice were produced at expected frequencies. Neither APP mRNA nor protein could be detected in these animals. Yet the homozygous APP mutant mice are fertile and do not show overt abnormalities at up to 12 weeks of age. Neuroanatomical studies of the brain did not reveal significant differences in the knockout mice as compared to the wild-type controls. These results argue against an essential function of APP in mouse embryonic and early neuronal development.

Amyloid beta-Protein Precursor↗
PubMed1995

beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity.

In several pedigrees of early onset familial Alzheimer's disease (FAD), point mutations in the beta-amyloid precursor protein (APP) gene are genetically linked to the disease. This finding implicates APP in the pathogenesis of Alzheimer's disease in these individuals. To understand the in vivo function of APP and its processing, we have generated an APP-null mutation in mice. Homozygous APP-deficient mice were viable and fertile. However, the mutant animals weighed 15%-20% less than age-matched wild-type controls. Neurological evaluation showed that the APP-deficient mice exhibited a decreased locomotor activity and forelimb grip strength, indicating a compromised neuronal or muscular function. In addition, four out of six homozygous mice showed reactive gliosis at 14 weeks of age, suggesting an impaired neuronal function as a result of the APP-null mutation.

Amyloid beta-Protein Precursor↗
PubMed1995

Integration by association: combining three-dimensional cues to extrinsic surface shape.

Surface shape is visually derived from multiple sources of three-dimensional (3-D) information. The apparent unity of the percept creates an assumption that there are perceptual processes that resolve and combine the different channels of information within some common 3-D representation. However, integration by the explicit conversion of the information from different sources into a common representation is computationally difficult and unnecessary. An alternative, integration by association, is discussed and related to a variety of experimental results on 3-D-cue conflict.

Association↗
PubMed1994

Induction of increased levels of proteoglycan fragments in synovial fluid (SF) and increased levels of stromelysin in cartilage, synovium and SF by intraarticular injection of canine monocyte conditioned medium into dogs.

OBJECTIVE: To study the effects of the intraarticular injection of canine monocyte conditioned medium (cMCM) into dogs on proteoglycan fragment and stromelysin levels in the joint. METHODS: cMCM was injected intraarticularly into dogs, and the levels of proteoglycan fragments in synovial fluid (SF) as well as stromelysin levels in cartilage, synovium, and SF were assessed after 12 h. RESULTS: There was a 4-fold increase of proteoglycan fragment levels and a 6-fold increase in stromelysin levels in SF, and a 4.4-fold increase in stromelysin levels in cartilage extracts. Elevated mRNA levels were detected in both synovium and cartilage. By immunofluorescence staining, stromelysin was localized in chondrocytes throughout the cartilage and in synovial cells. CONCLUSION: Intraarticular injection of cMCM stimulated the expression of stromelysin mRNA and protein in cartilage and synovium and caused marked increases in stromelysin protein and proteoglycan fragment levels in SF.

Animals↗
PubMed1993

The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins.

Little is known about genes that govern the development of the definitive endoderm in mammals; this germ layer gives rise to the intestinal epithelium and various other cell types, such as hepatocytes, derived from the gut. The discovery that the rat hepatocyte transcription factor HNF3 is similar to the Drosophila forkhead gene, which plays a critical role in gut development in the fly, led us to isolate genes containing the HNF3/forkhead (HFH) domain that are expressed in mouse endoderm development. We recovered mouse HNF3 beta from an embryo cDNA library and found that the gene is first expressed in the anterior portion of the primitive streak at the onset of gastrulation, in a region where definitive endoderm first arises. Its expression persists in axial structures derived from the mouse equivalent of Hensen's node, namely definitive endoderm and notochord, and in the ventral region of the developing neural tube. Expression of the highly related gene, HNF3 alpha, appears to initiate later than HNF3 beta and is first seen in midline endoderm cells. Expression subsequently appears in notochord, ventral neural tube, and gut endoderm in patterns similar to HNF3 beta. Microscale DNA binding assays show that HNF3 proteins are detectable in the midgut at 9.5 days p.c. At later stages HNF3 mRNAs and protein are expressed strongly in endoderm-derived tissues such as the liver. HNF3 is also the only known hepatocyte-enriched transcription factor present in a highly de-differentiated liver cell line that retains the capacity to redifferentiate to the hepatic phenotype. Taken together, these studies suggest that HNF3 alpha and HNF3 beta are involved in both the initiation and maintenance of the endodermal lineage. We also discovered a novel HFH-containing gene, HFH-E5.1, that is expressed transiently in posterior ectoderm and mesoderm at the primitive streak stage, and later predominantly in the neural tube. HFH-E5.1 is highly similar in structure and expression profile to the Drosophila HFH gene FD4, suggesting that HFH family members have different, evolutionarily conserved roles in development.

Amino Acid Sequence↗
PubMed1993

Choosing a career: why not nursing for more high school seniors?

Using a descriptive design, 641 college-bound high school seniors (CBHSS) in the Washington, DC, metropolitan area were surveyed to determine why nursing is not selected more frequently as a career. The findings indicated that the decision to choose or not choose nursing was significantly influenced by demographic characteristics (age, ethnicity, and race), past experiences with nurses/illness, and characteristics preferred in a future career. Those respondents who selected nursing cited wanting to help people, to do important work, and to work with a variety of people as important reasons for their choice. Those not choosing nursing indicated dislike of dying people and the salary as the main reasons for choosing another career.

Adolescent↗
PubMed1993

Developing a perinatal education program.

The process of assessing learning needs and designing and implementing educational offerings for perinatal families is discussed. Common areas of evaluation are examined, and sample questions are presented. Through careful application of teaching principles in conjunction with the nursing process, nurses can effectively develop comprehensive perinatal education programs.

Curriculum↗
PubMed1992

Antimicrobial action of nisin against Salmonella typhimurium lipopolysaccharide mutants.

The antimicrobial activity of nisin against outer membrane lipopolysaccharide mutants of Salmonella typhimurium LT2 was investigated. Nisin sensitivity was associated with the extent of saccharide deletions from the outer membrane core oligosaccharide. The results indicated that the core oligosaccharide in lipopolysaccharide plays a role in nisin sensitivity.

Lipopolysaccharides↗
PubMed1992

Low density lipoprotein is protected from oxidation and the progression of atherosclerosis is slowed in cholesterol-fed rabbits by the antioxidant N,N'-diphenyl-phenylenediamine.

The oxidative modification of low density lipoprotein (LDL) may play an important role in atherosclerosis. We found that the antioxidant N,N'-diphenyl-1,4-phenylenediamine (DPPD) inhibits in vitro LDL oxidation at concentrations much lower than other reported antioxidants. To test whether DPPD could prevent atherosclerosis, New Zealand White rabbits were fed either a diet containing 0.5% cholesterol and 10% corn oil (control group) or the same diet also containing 1% DPPD (DPPD-fed group) for 10 wk. Plasma total cholesterol levels were not different between the two groups, but DPPD feeding increased the levels of triglyceride (73%, P = 0.007) and HDL cholesterol (26%, P = 0.045). Lipoproteins from DPPD-fed rabbits contained DPPD and were much more resistant to oxidation than control lipoproteins. After 10 wk, the DPPD-fed animals had less severe atherosclerosis than did the control animals: thoracic aorta lesion area was decreased by 71% (P = 0.0007), and aortic cholesterol content was decreased by 51% (P = 0.007). Although DPPD cannot be given to humans because it is a mutagen, our results indicate that orally active antioxidants can have antiatherosclerotic activity. This strongly supports the theory that oxidized LDL plays an important role in the pathogenesis of atherosclerosis.

Administration, Oral↗
PubMed1991

Symbolic grouping versus simple cell models.

The apparent line-like structure in dot patterns derives substantially from the orientation defined by pairings of adjacent dots. Two alternative models have been proposed for making these pairings, one in which the individual dots are treated as discrete grouping tokens, and the second in which the pairing orientation derives from spatial summation by simple cell receptive fields. Contradictory evidence has been found both directly in support of, and directly against, both models. Much of the debate about these two models has hinged on the degree of linearity of summation expected in the simple cell model. Recent neurophysiological evidence changes the balance of the debate, invalidating certain earlier arguments based on linearity and providing a model way of showing that simple cells do indeed play a major, but not necessarily exclusive, role in dot groupings.

Analysis of Variance↗
PubMed1991

Combining binocular and monocular curvature features.

A study is reported of the perception of visual surfaces in wire-frame stimuli generated by combinations of monocular surface contours and binocular disparity that provide differing information about 3-D relief. Observers vary considerably in the relative contribution made by the binocular and monocular cues to the perception of overall 3-D form. Without training, many observers may entirely fail to perceive surface curvature from the binocular disparity patterns, interpreting the form of the surface only according to the monocular information. For other observers, both cues contribute to the end percept, with the monocular interpretation dominating where the disparity information indicates planarity and with disparity dominating where disparity information suggests curvature and the monocular interpretation suggests planarity. Where stereo and monocular interpretations indicate inconsistent surface curvature features at a common location, more complex resolution strategies are suggested.

Cues↗
PubMed1991

Nisin treatment for inactivation of Salmonella species and other gram-negative bacteria.

Nisin, produced by Lactococcus lactis subsp. lactis, has a broad spectrum of activity against gram-positive bacteria and is generally recognized as safe in the United States for use in selected pasteurized cheese spreads to control the outgrowth and toxin production of Clostridium botulinum. This study evaluated the inhibitory activity of nisin in combination with a chelating agent, disodium EDTA, against several Salmonella species and other selected gram-negative bacteria. After a 1-h exposure to 50 micrograms of nisin per ml and 20 mM disodium EDTA at 37 degrees C, a 3.2- to 6.9-log-cycle reduction in population was observed with the species tested. Treatment with disodium EDTA or nisin alone produced no significant inhibition (less than 1-log-cycle reduction) of the Salmonella and other gram-negative species tested. These results demonstrated that nisin is bactericidal to Salmonella species and that the observed inactivation can be demonstrated in other gram-negative bacteria. Applications involving the simultaneous treatment with nisin and chelating agents that alter the outer membrane may be of value in controlling food-borne salmonellae and other gram-negative bacteria.

Edetic Acid↗
PubMed1990

Selection and analysis of galactose metabolic pathway variants of a mouse liver cell line.

To study the genetic expression and regulation of galactose-metabolizing enzymes, we mutagenized the mouse liver H2.35 cell line and selected for cell clones resistant to the toxic galactose analog, 2-deoxy-D-galactose (2-DOG). One cloned line, designated H12.10, was stably resistant to high levels of 2-DOG and was completely deficient in galactokinase activity. Galactokinase activity and growth sensitivity to 2-DOG could be restored by transfecting H12.10 cells with a plasmid containing the Escherichia coli galactokinase (galK) gene fused to a eucaryotic promoter; thus, the 2-DOG selection could be directed against transfected recombinant constructs in a liver cell line. We also found that H2.35 cells could not utilize galactose as a primary carbon source because of a deficiency in galactose-1-phosphate uridyltransferase; a variant line of H2.35 cells selected in galactose medium expressed higher levels of uridyltransferase activity. Finally, we found that in all mammalian cell lines tested, galactokinase expression was the same whether the medium contained glucose, galactose, or both sugars. These studies demonstrate differences between mammalian cells and yeast cells in the regulation of gal enzymes, and they define different schemes for obtaining altered expression of genes in the galactose metabolic pathway. The isogenic liver cell lines described here can also serve as model systems for studying galactosemias, which are inherited disorders of galactose metabolism in humans.

Animals↗
PubMed1989

Differential contributions of circular and elongated spatial filters to the Café Wall illusion.

The Café Wall illusion is induced in part by the spatial filtering properties of circular-symmetric receptive fields at the retina, and in part by cortical processes, presumably that have elongated receptive fields. Two experiments are reported that address these two contributions. The first shows a reversal effect that is consistent with brightness-induction and related theories. The second shows extinction of the effect in a manner predicted by recent observations of gating nonlinearity in cortical cells.

Corpus Striatum↗
PubMed1989

Binocular depth from surfaces versus volumes.

Subjects were asked to compare the relative depths of two binocular targets embedded in different random dot stereogram backgrounds. The disparities of the background points were either randomized, corresponding to a scattering of points within a volume, or arranged according to a sawtooth (triangle-wave) disparity profile (i.e., a set of slanted planar surfaces separated by sharp depth discontinuities). When the targets were embedded in the random volume, their depths were perceived in accordance with their relative disparities. But when the target points were embedded in the sawtooth surfaces their depths were systematically misperceived in a manner predicted by the incorrect depth interpretation of the background points. Rather than seeing a sawtooth pattern, the background points resembled a staircase in depth, and the targets, which appeared embedded in different steps, were misjudged in depth accordingly. The effect suggests a distinction between the depth processing of isolated binocular features and those associated with continuous surfaces.

Attention↗
PubMed1989

The analogy between stereo depth and brightness.

Apparent depth in stereograms exhibits various simultaneous-contrast and induction effects analogous to those reported in the luminance domain. This behavior suggests that stereo depth, like brightness, is reconstructed, ie recovered from higher-order spatial derivatives or differences of the original signal. The extent to which depth is analogous to brightness is examined. There are similarities in terms of contrast effects but dissimilarities in terms of the lateral inhibition effects traditionally attributed to underlying spatial-differentiation operators.

Color Perception↗