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Biomedical subjects

E N Johnson

Publications and source records attributed to E N Johnson.

10 recordsLinked to original sources
PubMed2001

Role of 'platelet-type' 12-lipoxygenase in skin carcinogenesis.

Murine and human skin express an abundance of lipoxygenase isoforms whose functions are not understood. Substantial data have implicated a role for the 'platelet-type' 12-lipoxygenase (P-12LO) metabolite, 12(S)-hydroxy-eicosatetraenoic acid (12-HETE), in a variety of tumor functions. Using P-12LO deficient mice, we sought to examine the role of the P-12LO pathway in tumor initiation and progression. Two distinct genetic strains of P-12LO deficient and wild-type mice, B6/129 Sv and SENCAR, were evaluated in two-stage carcinogenesis experiments. Carcinoma incidence was significantly reduced in the P-12LO deficient mice of the B6/129 Sv background but not the SENCAR-backcrossed mice. In contrast, papilloma incidence was reduced on the SENCAR background but not in the B6/129 Sv strain mice. A separate experiment employing a complete carcinogenesis protocol failed to find any difference in papilloma or carcinoma incidence. Overall, these data suggest that the P-12LO pathway may contribute to tumor incidence and progression in two-stage, but not complete, carcinogenesis, depending on the genetic background.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

The spatial transformation of color in the primary visual cortex of the macaque monkey.

Perceptually, color is used to discriminate objects by hue and to identify color boundaries. The primate retina and the lateral geniculate nucleus (LGN) have cell populations sensitive to color modulation, but the role of the primary visual cortex (V1) in color signal processing is uncertain. We re-evaluated color processing in V1 by studying single-neuron responses to luminance and to equiluminant color patterns equated for cone contrast. Many neurons respond robustly to both equiluminant color and luminance modulation (color-luminance cells). Also, there are neurons that prefer luminance (luminance cells), and a few neurons that prefer color (color cells). Surprisingly, most color-luminance cells are spatial-frequency tuned, with approximately equal selectivity for chromatic and achromatic patterns. Therefore, V1 retains the color sensitivity provided by the LGN, and adds spatial selectivity for color boundaries.

Action Potentials↗
PubMed1999

Basal transepidermal water loss is increased in platelet-type 12-lipoxygenase deficient mice.

The roles of fatty acids in the skin have been under investigation since early reports of the phenotypic abnormalities of mice fed a diet deficient in essential fatty acids. Little is known about the functional significance of fatty acid metabolism by lipoxygenases in epidermis. Here, we have examined the role of platelet-type 12-lipoxygenase which converts arachidonic acid to the oxygenated metabolite 12-hydroperoxyeicosatetraenoic acid, in the skin using platelet-type 12-lipoxygenase-deficient mice generated by gene targeting. Platelet-type 12-lipoxygenase in wild-type mice was localized to the stratum granulosum by immunohistochemical analysis. Platelet-type 12-lipoxygenase-deficient mice lacked immunodetectable platelet-type 12-lipoxygenase in platelets and epidermis, appeared grossly normal, and exhibited an increase in basal transepidermal water loss without alteration in basal mitotic activity. Water loss and mitotic activity in mice with an acetone-disrupted membrane barrier were normal. No defect in ultrastructural properties or content of major fatty acids in dorsal skin or ear inflammation response was apparent in platelet-type 12-lipoxygenase-deficient mice. These results indicate that the platelet-type 12-lipoxygenase pathway in mice is partly responsible for normal permeability barrier function but the mechanism awaits further elucidation.

Animals↗
PubMed1999

High-frequency steering maneuvers mediated by tactile cues: antennal wall-following in the cockroach.

Cockroaches (Periplaneta americana) use their antennae to detect a wall and to maintain a constant distance from it as they walk or run along it. The faster they run, the closer they position themselves to the wall. They also use their antennae to detect and follow multiple accordion-like projections in the wall. They can make up to 25 body turns s-1 for short periods during rapid running to follow such wall projections. Each turn apparently involves a change in stepping direction. These turns help to avoid collisions with the outward projections, while keeping the body close to the wall. Sensory inputs from the flagellum of the antenna, and not from its base, appear to evoke the turns in response to wall projections. These flagellar inputs appear to report the position along the antenna of its contact with the wall and/or the position of the consequent antennal bend. This flagellar information constitutes a one-dimensional sensory map, with location along the map indicating the distance to the wall.

Animals↗
PubMed1998

Increased platelet sensitivity to ADP in mice lacking platelet-type 12-lipoxygenase.

Arachidonic acid metabolism is one of several mechanisms culminating in the production of an agonist for platelet activation and recruitment. Although the proaggregatory role of thromboxane A2, a product of the aspirin-inhibitable cyclooxygenase, is well established, relatively little is known regarding the biological importance of arachidonic acid metabolism via the 12-lipoxygenase (P-12LO) pathway to 12-hydro(pero)xyeicosatetraenoic acid. We observed that platelets obtained from mice in which the P-12LO gene has been disrupted by gene targeting (P-12LO-/-) exhibit a selective hypersensitivity to ADP, manifested as a marked increase in slope and percent aggregation in ex vivo assays and increased mortality in an ADP-induced mouse model of thromboembolism. The hyperresponsiveness to ADP is independent of dense granule release, cyclooxygenase-derived eicosanoid synthesis, and protein kinase C activity. The addition of 12-hydroxyeicosatetraenoic acid to P-12LO-/- platelet-rich plasma rescues the hyperresponsive phenotype resulting in a diminished ADP-induced aggregation profile. The enhanced ADP sensitivity of P-12LO-/- mice appears to reveal a mechanism by which a product of the P-12LO pathway suppresses platelet activation by ADP.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1994

Role of leukotrienes revealed by targeted disruption of the 5-lipoxygenase gene.

Leukotrienes constitute a class of potent biological mediators of inflammation and anaphylaxis (for reviews see refs 1 and 2). Their biosynthesis derives from 5-lipoxygenase-catalysed oxygenation of arachidonic acid in granulocytes, macrophages and mast cells. To examine the physiological importance of leukotrienes, we have disrupted the 5-lipoxygenase gene by homologous recombination in embryonic stem cells. 5-Lipoxygenase-deficient (5LX-/-) mice develop normally and are healthy. They show a selective opposition to certain inflammatory insults. Although there is no difference in their reaction to endotoxin shock, the 5LX-/- animals resist the lethal effects of shock induced by platelet-activating factor. Reaction to ear inflammation induced by phorbol ester is normal, whereas inflammation induced by arachidonic acid is markedly reduced. Contrasts were also found in two models of leukocyte chemotaxis in vivo. The phenotype of 5LX-/- mice under injurious insult identifies the role for leukotrienes in the pathophysiology of select inflammatory states.

Anaphylaxis↗
PubMed1978

Sixth graders can take blood pressures.

A curriculum guide entitled "Heart Health Curriculum Guide" was developed with and by teachers in Peabody Public Schools under a Massachusetts Public Health grant to the American Heart Association. The 67-page manual describes the format of the 12-hour teacher workshop, background physiology of heart/circulatory system, hypertension risk factors, a set of 20 lessons, and evaluating procedures. (Copies may be obtained for $3.00 by writing the corresponding author.) As a result of teaching this unit, sixth grade students in each school ran a Blood Pressure Screening Clinic for their parents and school staff.

Blood Pressure Determination↗