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Biomedical subjects

D Somers

Publications and source records attributed to D Somers.

13 recordsLinked to original sources
PubMed1996

Subthreshold facilitation and suppression in primary visual cortex revealed by intrinsic signal imaging.

Neurons in primary visual cortex (area 17) respond vigorously to oriented stimuli within their receptive fields; however, stimuli presented outside the suprathreshold receptive field can also influence their responses. Here we describe a fundamental feature of the spatial interaction between suprathreshold center and subthreshold surround. By optical imaging of intrinsic signals in area 17 in response to a stimulus border, we show that a given stimulus generates activity primarily in iso-orientation domains, which extend for several millimeters across the cortical surface in a manner consistent with the architecture of long-range horizontal connections in area 17. By mapping the receptive fields of single neurons and imaging responses from the same cortex to stimuli that include or exclude the aggregate suprathreshold receptive field, we show that intrinsic signals strongly reveal the subthreshold surround contribution. Optical imaging and single-unit recording both demonstrate that the relative contrast of center and surround stimuli regulates whether surround interactions are facilitative or suppressive: the same surround stimulus facilitates responses when center contrast is low, but suppresses responses when center contrast is high. Such spatial interactions in area 17 are ideally suited to contribute to phenomena commonly regarded as part of "higher-level" visual processing, such as perceptual "popout" and "filling-in."

Animals↗
PubMed1995

Anti-phase solutions in relaxation oscillators coupled through excitatory interactions.

Relaxation oscillators interacting via models of excitatory chemical synapses with sharp thresholds can have stable anti-phase as well as in-phase solutions. The mechanism for anti-phase demonstrated in this paper relies on the fact that, in a large class of neural models, excitatory input slows down the receiving oscillator over a portion of its trajectory. We analyze the effect of this "virtual delay" in an abstract model, and then show that the hypotheses of that model hold for widely used descriptions of bursting neurons.

Animals↗
PubMed1995

Effects of contact sensitizers neomycin sulfate, benzocaine and 2,4-dinitrobenzene 1-sulfonate, sodium salt on viability, membrane integrity and IL-1 alpha mRNA expression of cultured normal human keratinocytes.

The toxic effect of three potential contact sensitization chemicals [the aminoglycosidic antibiotic neomycin sulfate, the local anaesthetic benzocaine and the primary sensitizer 2,4-dinitrobenzene 1-sulfonate, sodium salt (DNBS)], on cultured human keratinocytes was examined. The three chemicals were compared with respect to their cytotoxic potential (determined by crystal violet staining assay), their membrane disruptive potential ([3H]arachidonic acid release assay), and their effects on interleukin 1 alpha (IL-1 alpha) mRNA expression [reverse transcription-polymerase chain reaction (RT-PCR)]. At the concentrations used, neomycin sulfate (0.004-0.32%) and benzocaine (0.0165-0.165%) did not show relevant cytotoxicity or membrane perturbation. On the other hand, DNBS (0.001-1%) caused a significant dose-dependent cytotoxic response at concentrations higher than 0.1%, while the [3H]arachidonic acid release assay indicated absence of membrane perturbation activity in all the range of DNBS concentrations examined. The effects of the three sensitizers on IL-1 alpha mRNA expression were varied; neomycin sulfate caused a dose-dependent induction of IL-1 alpha mRNA, benzocaine did not significantly affect its signal, and DNBS suppressed IL-1 alpha gene expression.

Arachidonic Acid↗
PubMed1995

High resolution structures of HIV-1 RT from four RT-inhibitor complexes.

We have determined the structures of four complexes of HIV-1 reverse transcriptase with non-nucleoside inhibitors, three fully refined at high resolution. The highest resolution structure is of the RT-nevirapine complex which has an R-factor of 0.186 and a root-mean-square bond length deviation of 0.015 A for all data to 2.2 A. The structures reveal a common mode of binding for these chemically diverse compounds. The common features of binding are largely hydrophobic interactions and arise from induced shape complementarity achieved by conformational rearrangement of the enzyme and conformational/configurational rearrangement of the compounds.

Amino Acid Sequence↗
PubMed1993

Rapid synchronization through fast threshold modulation.

Synchronization properties of locally coupled neural oscillators were investigated analytically and by computer simulation. When coupled in a manner that mimics excitatory chemical synapses, oscillators having more than one time scale (relaxation oscillators) are shown to approach synchrony using mechanisms very different from that of oscillators with a more sinusoidal waveform. The relaxation oscillators make critical use of fast modulations of their thresholds, leading to a rate of synchronization relatively independent of coupling strength within some basin of attraction; this rate is faster for oscillators that have conductance-based features than for neural caricatures such as the FitzHugh-Nagumo equations that lack such features. Computer simulations of one-dimensional arrays show that oscillators in the relaxation regime synchronize much more rapidly than oscillators with the same equations whose parameters have been modulated to yield a more sinusoidal waveform. We present a heuristic explanation of this effect based on properties of the coupling mechanisms that can affect the way the synchronization scales with array length. These results suggest that the emergent synchronization behavior of oscillating neural networks can be dramatically influenced by the intrinsic properties of the network components. Possible implications for perceptual feature binding and attention are discussed.

Computer Simulation↗
PubMed1991

Action of gold sodium thiomalate on experimental thrombosis in vivo.

In order to study the effect of gold compounds on the action of thrombin in vivo, experiments were performed to measure platelet survival and the weight of thrombus formation in experimental models of intra-aortic thrombosis by two indwelling aortic catheter methods. We have called these the long and short catheter methods. Platelet survival was reduced in all gold-treated and control animals which had indwelling aortic catheters. In the long catheter model, New Zealand White male rabbits were treated with one of the following: gold sodium thiomalate, sterile water, gold thioglucose, gold sodium thiosulfate, disodium thiomalate. Gold sodium thiomalate-treated rabbits had a reduced weight of experimentally induced intra-aortic thrombi compared with animals treated with sterile water or equimolar concentrations of gold thioglucose, gold sodium thiosulfate, or disodium thiomalate. This reduction in thrombus weight in the animals treated with gold sodium thiomalate was not reflected by changes in platelet survival or fibrinolysis. The serum gold levels achieved in these in vivo experiments was in the range of 5.0 X 10(-5) to 1.0 X 10(-4) M. These values are comparable to levels which can be achieved in human subjects immediately after a gold injection. In the short catheter model, New Zealand White male rabbits were treated with either gold sodium thiomalate, gold thioglucose, disodium thiomalate, or auranofin. Controls were given either water or 0.05% chlorocresol. Water-treated and gold sodium thiomalate-treated animals were also given 51Cr-labeled platelets and 125I-fibrinogen before insertion of the catheter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The relation among vessel injury, thrombus formation, and platelet survival in rabbits.

Continuous or repeated injury of rabbit aortae by indwelling vascular catheters caused the deposition of platelets on the injured vessels and the formation of thrombi rich in platelets and fibrin at sites where flow was most disturbed and injury was most extensive. Incorporation of 51Cr platelets into the thrombi reached a maximum between 3 and 24 hr. The platelet-fibrin-rich thrombi remained reactive to circulating platelets for at least 14 days. Continuing reactivity of thrombi and the turnover of platelets in the thrombi were accompanied by an increase in the proportion of platelets that separated in the least dense fraction on Stractan density gradients. Platelet survival was also shortened (43.5 +/- 5.9 hr in animals with catheters, compared with 62.6 +/- 4.5 hr in animals with a sham operation), indicating that some platelets that had taken part in thrombus formation or had interacted with the injured vessel wall were rapidly cleared from the circulation. Platelets from rabbits that had had indwelling aortic catheters in place for 3 or 6 days survived significantly longer than those from animals with a sham operation upon injection of the platelets into normal animals; thus, continuous turnover of platelets on injured vessels and thrombi, and the clearance of altered platelets, leads to a population of younger platelets that survive longer. The continuing reactivity of thrombi may in part account for repeated occlusive episodes in vascular disease. The contribution of thrombin generation and fibrin formation to the platelet-rich thrombi is substantial and warrants the ongoing evaluation of treatment with a combination of anticoagulant and antiplatelet agents in arterial thrombosis and in thrombus formation on vascular catheters.

Animals↗
PubMed1989

Disposition of 2,4-dichlorophenoxyacetic acid dimethylamine by Fischer 344 rats dosed orally and dermally.

The dimethylamine salt of 14C-ring-labeled 2,4-D was administered to Fischer 344 rats orally (1 and 0.4 mg/kg body weight) and dermally (10 mg/kg body weight). Absorption, distribution, and elimination were determined from 14C-labeled 2,4-D in blood, tissues, and excreta. Quantitatively, most of the orally administered dose (94-96%) became systemically available within 6 h. Following dermal administration 10% of the dose became systemically available over 72 h. However, peak concentrations in blood and kidneys were achieved within 30 min of dosing by either route. By 1.5 h after dosing, 2,4-D concentrations in blood, muscle, liver, and kidneys had decreased in both the orally dosed and dermally dosed animals. Between 2 and 8 h, the blood, muscle, liver and kidney concentrations in dermally dosed animals maintained a plateau while urinary excretion increased, presumably due to continued absorption of 2,4-D from the skin. The concentrations in orally dosed animals continued to decrease. Following 7 h of dermal exposure, skin cleansing removed about 63% of the applied dose; about 17% of the applied dose remained at the site of dermal dosing. At 8 h, 2,4-D concentrations in blood, muscle, liver, and kidneys of dermally dosed animals began to decrease, most likely a result of the removal of the reservoir on the skin. However, 2,4-D continued to be absorbed from skin site, resulting in a slower decline of the 2,4-D concentrations in these tissues over remainder of the 72-h study period. By comparison, in animals that had been orally dosed, the absorbed dose was almost completely excreted within 24 h.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1985

Fine-needle aspiration biopsy in the management of solid breast tumors.

Fine-needle aspiration biopsy (FNA) is a cost-effective and clinically reliable tool in the management of palpable solid breast lesions. Review of 369 FNA biopsy specimens revealed an accuracy of 92%. The sensitivity was 78% and the specificity was 100%. There were no false-positive results. Positive predictive value was 100%, and negative predictive value was 78%. A positive FNA biopsy result, which confirms a clinical (physical examination and mammography) impression of carcinoma, can be the basis for planning and performing a definitive procedure. Despite the absence of false-positive results, we have not proceeded with a definitive surgical procedure if an FNA biopsy result disagreed with our clinical impression. Fine-needle aspiration biopsy may be used to reassure and support both the patient's and the surgeon's decision not to perform a biopsy of "subsuspicious lesions." A negative FNA biopsy result does not exonerate the clinically suspicious lesion.

Biopsy, Needle↗
PubMed1984

Heterogeneity of neurons in the subnucleus interpolaris of the cat.

Fluorescent dyes were used to determine if neurons in the feline subnucleus interpolaris of the spinal trigeminal nucleus project to more than one target via axon collaterals. Either Fast Blue or True Blue was injected into the ventrobasal thalamus while Nuclear Yellow later was deposited into either the principal trigeminal nucleus or the cerebellum. In general, numerous neurons in the subnucleus interpolaris were labeled by a single dye after these injections, but only a few were labeled with two dyes, and the latter only after the combination of injections were into the thalamus and the principal nucleus on the opposite side. These data suggest that independent populations of neurons in the subnucleus interpolaris project to these targets.

Animals↗
PubMed1983

Effect of aspirin and sodium salicylate on thrombosis, fibrinolysis, prothrombin time, and platelet survival In rabbits with indwelling aortic catheters.

We have studied the effect of different doses of aspirin on platelet function, PGI2 formation, platelet survival, thrombosis, fibrinolysis, and prothrombin time in rabbits with indwelling aortic catheters. The thrombi formed around indwelling aortic catheters were found to have a large fibrin component, and their formation was inhibited by heparin administration. Thus, in these experiments we examined the effect of aspirin (a weak inhibitor of thrombin-mediated platelet aggregation) under conditions in which thrombin was a major factor in the initiation and growth of the thrombi. Only very high doses of aspirin tended to inhibit thrombus formation over the 5-day period of observation, and a statistically significant inhibition of thrombus formation was produced by equivalent concentrations of sodium salicylate. The failure of high doses of aspirin to achieve a significant inhibition of thrombosis under the conditions of these experiments (whereas an equivalent dose of sodium salicylate was inhibitory) could be due to aspirin inhibition of PGI2 formation. Shortened platelet survival was not affected by aspirin treatment or the dose sodium salicylate that inhibited thrombus formation. The tendency to inhibit thrombus formation appeared to be unrelated to an effect on platelets but was associated with prolongation of the one-stage prothrombin time and increased whole blood fibrinolytic activity; doses of aspirin that inhibited platelet aggregation in response to sodium arachidonate or collagen, and PGI2 formation by the vessel wall, did not have a significant effect on the amount of thrombus present at 5 days. However, the high doses of aspirin that inhibited PGI2 formation were associated with a tendency to increased thrombus formation during the first 3 hr after insertion of the catheter. The results of these experiments show that when thrombin is an important factor in the formation of thrombi, aspirin is a weak inhibitor of thrombosis unless doses are used that provide sufficient salicylate to interfere with blood coagulation and promote whole blood fibrinolytic activity. These results also show that thrombus formation can be inhibited without an apparent change in platelet survival.

Animals↗
PubMedDate not supplied

Platelet survival and thrombosis.

This study examined the relation among platelet survival, thrombosis, and repeated vessel injury. With the use of 51Cr-labeled platelets, indwelling aortic catheters were shown to reduce platelet survival in rabbits and rats. In rabbits, thrombi were observed mainly at the aortic bifurcation and at the tip of the catheter. The amount of thrombus that formed in rabbits with short and long catheters was similar, but platelet survival was shortened only in rabbits with short and long catheters was similar, but platelet survival was shortened only in rabbits with long indwelling aortic catheters. In rats, the aortic catheters did not cause thrombosis, and platelet survival was shortened significantly in rats with both short and long catheters, but was more pronounced in animals with longer catheters. In both rabbits and rats, long aortic catheters caused more extensive vessel injury than the short catheters and this was associated with greater platelet interaction with the vessel wall. Platelet survival cannot be used as an estimate of thrombus formation, but may reflect the extent and frequency of vessel wall injury. thus, shortened platelet survival may represent increased platelet interaction with the damaged arterial wall and increased platelet consumption.

Animals↗