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Responses of neurons in the cat posteromedial lateral suprasylvian cortex to moving texture patterns.

The posteromedial lateral suprasylvian cortex represents a point of convergence between the geniculostriate and extrageniculostriate visual pathways. Given its purported role in motion analysis and the conflicting reports regarding the texture sensitivity of this area, we have investigated the response properties of cells in PMLS to moving texture patterns ("visual noise"). In contrast to previous reports, we have found that a large majority of cells (80.1%) responds to the motion of a texture pattern with sustained discharges. In general, responses to noise were more broadly tuned for direction compared to gratings; however, direction selectivity appeared more pronounced in response to noise. The majority of cells was selective for drift velocity of the noise pattern (mean optimal velocity: 26.7 degrees /s). Velocity tuning was comparable to that of its principal thalamic input, the lateral posterior pulvinar nucleus. In general, responsiveness of cells in the posteromedial lateral suprasylvian cortex increased with increasing texture element size, although some units were tuned to smaller element sizes than the largest presented. Finally, the magnitude of these noise responses was dependent on the area of the visual field stimulated. In general, a stimulus corresponding to roughly twice the size of the receptive field was required to elicit an equivalent half-maximal response to that for gratings. The results of this study indicate that the majority of cells in the posteromedial lateral suprasylvian cortex can be driven by the motion of a fine texture field, and highlight the importance of this area in motion analysis.

Animals↗

Response of generalized penicillin epilepsy in the cat to ethosuximide and diphenylhydantoin.

The effects of ethosuximide and diphenylhydantoin sodium on feline generalized penicillin epilepsy, a model of human generalized corticoreticular (centreccephalic) epilepsy, were significantly reduced following administration of ethosuximide with plasma levels of 60 mug per milliliter, and there was a linear correlation between the plasma level and antiephilepileptic effect (p less than 0.01). Diphenylhydantoin produced a lesser reduction in epileptic activity, and there was no correlation between the plasma level and effect. Four cats that received both drugs successively responded well to ethosuximide, while only two responded to diphenylhdantoin. The good response to ethosuximide is in accord with clinical experience in human generalized corticoreticular epilepsy.

Animals↗

Use of cholinesterase activity in monitoring organophosphate pesticide exposure of cattle produced in tropical areas.

The use of cholinesterase activity as a biochemical method for monitoring organophosphate pesticide exposure in cattle is described herein. Determination of cholinesterase activity of whole blood, erythrocyte, and plasma was carried out according to the Ellman modified kinetic method. The mean baseline acetylcholinesterase activities of 9.549 +/- 3.619 IU/mL in whole blood, 9.444 +/- 3.006 IU/mL in erythrocytes, and 0.149 +/- 0.063 IU/mL in plasma were estimated for steers from the control group. Results of multivariate analysis showed that the general responses between the control and experimental groups (in vivo, monitoring and case studies) treated with Coumaphos and Fenthion were statistically different, and the general responses of these experimental groups were statistically different over time as well. Among the fractions that were analyzed, the erythrocyte acetylcholinesterase activity could be adequate for the diagnosis of exposure or acute poisoning in cattle as it showed a good within-run and between-run precision with CVs <10% better than those in plasma.

Acetylcholinesterase↗

Serotonin transporter gene promoter polymorphism predicts SSRI response in generalized social anxiety disorder.

OBJECTIVES: To determine whether variation in the serotonin transporter gene promoter (5HTTLPR) influences the efficacy of selective serotonin reuptake inhibitors (SSRIs) in generalized social anxiety disorder (GSAD). METHODS: Consecutive series of N=32 patients with DSM-IV GSAD for whom DNA and standardized outcome data from a 12-week SSRI trial were available. After ensuring that neither clinical response [clinical global impression of change scale (CGI-C)] nor 5HTTLPR genotype was confounded by ethnicity or sex, we determined whether the number of copies (0, 1, or 2) of hi-risk alleles using either the diallelic L-S system or the triallelic La-Lg-S system, predicted response and change in Liebowitz social anxiety scale (LSAS) and brief social phobia scale (BSPS) scores during SSRI treatment. RESULTS: Twenty-one patients (66%) were responders to SSRI (i.e., CGI-C much or very much improved). A trend was seen for a linear association between 5HTTLPR genotype and likelihood of response to SSRI: diallelic classification L/L 7/8 (88%), L/S 12/18 (67%), S/S 2/6 (33%), p=0.051; triallelic classification L'/L' 4/5 (80%), L'/S' 14/19 (74%), S'/S' 3/8 (38%), p=0.093. Reduction in LSAS (and BSPS) scores during SSRI treatment was significantly (p<0.02) associated with 5HTTLPR genotype using either the diallelic or triallelic classification. CONCLUSIONS: Variation in a functional polymorphism known to influence serotonin reuptake is associated with SSRI response in patients with GSAD. Independent replication in larger samples is required before the predictive utility of this information can be confirmed and generalized to clinical settings.

Adult↗

Strain-specific differences in mouse hepatic wound healing are mediated by divergent T helper cytokine responses.

Hepatic fibrosis represents the generalized response of the liver to injury and is characterized by excessive deposition of extracellular matrix. The cellular basis of this process is complex and involves interplay of many factors, of which cytokines are prominent. We have identified divergent fibrosing responses to injury among mouse strains and taken advantage of these differences to examine and contrast T helper (Th)-derived cytokines during fibrogenesis. Liver injury was induced with carbon tetrachloride, fibrosis was quantitated, and Th1/Th2 cytokine mRNAs measured. Liver injury in BALB/c mice resulted in severe fibrosis, whereas C57BL/6 mice developed comparatively minimal fibrosis. Fibrogenesis was significantly modified in T and B cell-deficient BALB/c and C57BL/6 severe combined immunodeficient (SCID) mice compared with wild-type counterparts, suggesting a role of Th subsets. Fibrogenic BALB/c mice exhibited a Th2 response during the wounding response, whereas C57BL/6 mice displayed a Th1 response, suggesting that hepatic fibrosis is influenced by different T helper subsets. Moreover, mice lacking interferon gamma, which default to the Th2 cytokine pathway, exhibited more pronounced fibrotic lesions than did wild-type animals. Finally, shifting of the Th2 response toward a Th1 response by treatment with neutralizing anti-interleukin 4 or with interferon gamma itself ameliorated fibrosis in BALB/c mice. These data support a role for immune modulation of hepatic fibrosis and suggest that Th cytokine subsets can modulate the fibrotic response to injury.

Animals↗

The CssRS two-component regulatory system controls a general secretion stress response in Bacillus subtilis.

Bacillus species are valuable producers of industrial enzymes and biopharmaceuticals, because they can secrete large quantities of high-quality proteins directly into the growth medium. This requires the concerted action of quality control factors, such as folding catalysts and 'cleaning proteases'. The expression of two important cleaning proteases, HtrA and HtrB, of Bacillus subtilis is controlled by the CssRS two-component regulatory system. The induced CssRS-dependent expression of htrA and htrB has been defined as a protein secretion stress response, because it can be triggered by high-level production of secreted alpha-amylases. It was not known whether translocation of these alpha-amylases across the membrane is required to trigger a secretion stress response or whether other secretory proteins can also activate this response. These studies show for the first time that the CssRS-dependent response is a general secretion stress response which can be triggered by both homologous and heterologous secretory proteins. As demonstrated by high-level production of a nontranslocated variant of the alpha-amylase, AmyQ, membrane translocation of secretory proteins is required to elicit this general protein secretion stress response. Studies with two other secretory reporter proteins, lipase A of B. subtilis and human interleukin-3, show that the intensity of the protein secretion stress response only partly reflects the production levels of the respective proteins. Importantly, degradation of human interleukin-3 by extracellular proteases has a major impact on the production level, but only a minor effect on the intensity of the secretion stress response.

Bacillus subtilis↗

Serotonergic receptor antagonists alter responses to general anaesthetics in rats.

Serotonergic neurotransmission is involved in controlling arousal levels in humans and other animals. Here, the effects of serotonergic receptor antagonists on the induction and depth of anaesthesia produced by three different general anaesthetics were investigated. Rats were pretreated (i.p.) with either methiothepin (1.5 mg kg(-1)), mianserin (5 mg kg(-1)), ketanserin (7 mg kg(-1)) or saline. Subsequently, successive, cumulative doses (i.p.) of either ketamine (final, cumulative dose of 350 mg kg(-1)), sodium pentobarbital (final dose 77 mg kg(-1)), or chloral hydrate (final dose 600 mg kg(-1)) were administered. The response to the anaesthetics was measured using a behavioural test battery assessing nocifensive reflexes and hypnotic state. Pre-treatment with methiothepin enhanced responses to all three anaesthetics; mianserin enhanced responses to chloral hydrate. These results show that some serotonergic receptor antagonists change anaesthetic requirements, resulting in enhanced anaesthesia to hypnotics with different mechanisms of action.

Anesthetics, General↗

Response of general practitioners to computer-generated critiques of hypertension therapy.

We recently have shown that a computer system, known as HyperCritic, can successfully audit general practitioners' treatment of hypertension by analyzing computer-based patient records. HyperCritic reviews the electronic medical records and offers unsolicited advice. To determine which unsolicited advice might be perceived as inappropriate, builders of programs such as HyperCritic need insight into providers' responses to computer-generated critique of their patient care. Twenty medical charts, describing in total 243 visits of patients with hypertension, were audited by 8 human reviewers and by the critiquing-system HyperCritic. A panel of 14 general practitioners subsequently judged the relevance of those critiques on a five-point scale ranging from relevant critique to erroneous or harmful critique. The panel judged reviewers' comments to be either relevant or somewhat relevant in 61 to 68% of cases, and either erroneous or possibly erroneous in 15 to 18%; the panel judged HyperCritic's comments to be either relevant or somewhat relevant in 65% of cases, and either erroneous or possibly erroneous in 16%. Comparison of individual members of the panel showed large differences; for example, the portion of HyperCritic's comments judged relevant ranged from 0 to 82%. We conclude that, from the perspective of general practitioners, critiques generated by the critiquing system HyperCritic are perceived equally beneficial as critiques generated by human reviewers. Different general practitioners, however, judge the critiques differently. Before auditing systems based on computer-based patient records that are acceptable to practitioners can be introduced, additional studies are needed to evaluate the reasons a physician may have for judging critiques to be irrelevant, and to evaluate the effect of critiques on physician behavior.

Artificial Intelligence↗

Challenge response predictors. General principles.

Environmental challenges offer a potential method for predicting hypertension. They could be nutritional (eg, an increased salt load), behavioral (eg, a mental arithmetic task), or physical (eg, an exercise test) in nature. An ideal challenge test should be simple to administer, easily standardized, and with a response that can be precisely quantified. The response is best expressed as a change score from the baseline level, and should be reproducible over time. For the prediction of hypertension, blood pressure is the usual response measure, although others, such as heart rate, are possible. The response should have predictive value independently of other known predictors, including the baseline level. The dependent variables might be future blood pressure, target organ damage, or morbid events.

Behavior↗

Heat-shock and general stress response in Bacillus subtilis.

The induction of stress proteins is an important component of the adaptional network of a non-growing cell of Bacillus subtilis. A diverse range of stresses such as heat shock, salt stress, ethanol, starvation for oxygen or nutrients etc. induce the same set of proteins, called general stress proteins. Although the adaptive functions of these proteins are largely unknown, they are proposed to provide general and rather non-specific protection of the cell under these adverse conditions. In addition to these non-specific general stress proteins, all extracellular signals induce a set of specific stress proteins that may confer specific protection against a particular stress factor. In B. subtilis at least three different classes of heat-inducible genes can be defined by their common regulatory characteristics: Class I genes, as exemplified by the dnaK and groE operons, are most efficiently induced by heat stress. Their expression involves a sigma A-dependent promoter, an inverted repeat (called the CIRCE element) highly conserved among eubacteria, and probably a repressor interacting with the CIRCE element. The majority of general stress genes (class II, more than 40) are induced at sigma B-dependent promoters by different growth-inhibiting conditions. The activation of sigma B by stress or starvation is the crucial event in the induction of this large stress regulon. Only a few genes, including Ion, clpC, clpP, and ftsH, can respond to different stress factors independently of sigma B or CIRCE (class III). Stress induction of these genes occurs at promoters presumably recognized by sigma A and probably involves additional regulatory elements which remain to be defined.

Bacillus subtilis↗

Rewarding safety belt usage at an industrial setting: Tests of treatment generality and response maintenance.

An incentive program to motivate seat belt use was implemented at a large munitions plant. Seat belt usage was assessed daily at an entrance/exit gate of the industrial complex when employees arrived for work in the morning and departed in the afternoon. During treatment incentive fliers, which prompted seat belt usage and gave belt wearers opportunities to win prizes, were distributed only in the afternoon. Seat belt wearing increased from baseline means of 20.4% and 17.3% during the morning and afternoon, respectively, to averages of 55.5% during afternoon departures and 31.1% during morning arrivals. During follow-up, mean belt use dropped almost to baseline levels. Categorizing vehicles according to driver sex and license plate number enabled a study of belt wearing practices of individuals, and revealed that the incentive program influenced some drivers to wear their seat belts during morning arrival when incentives were not distributed (i.e., treatment generalization) and during a follow-up period after the incentives were withdrawn (i.e., response maintenance).

Journal Article↗

[The influence of buprenorphine and tramadol on the postoperative CO2 response after general anaesthesia (author's transl)].

The degree of respiratory depression caused by buprenorphine and tramadol were studied in two groups of 25 patients each by means of Read's re-breathing technique. The estimations were made during the immediate postoperative stage in order to include potential residual effects of the general anaesthesia. The slope of the CO2 curve as a measure of respiratory depression decreased by 27 per cent after administration of 0.3 mg of buprenorphine, a reduction which equals that produced by potent morphine-type analgesics. The response to 50 mg of tramadol was a non-significant decrease by 3 per cent. At doses mentioned buprenorphine produced reliable pain relief, whereas with tramadol the failure rate was 28 per cent. There was no difference between the two drugs in respect of circulatory reactions and side-effects. Despite its depressing effect on the respiration (an action it shares with all potent analgesics) buprenorphine is a very useful analgesic because it provides excellent pain relief, has no or only minimal addictive properties and is not subject to the Dangerous Drugs Act.

Analgesia↗

Generalization in response to mate recognition signals.

Females usually exhibit strong and unequivocal recognition of conspecific mating signals and reject those of other sympatric heterospecifics. However, most species are allopatric with one another, and the degree to which females recognize mating signals of allopatric species is more varied. Such mating signals are often rejected but are sometimes falsely recognized as conspecific. We studied the dynamics of mate recognition in female túngara frogs (Physalaemus pustulosus) in response to a series of calls that were intermediate between the conspecific and each of five allopatric-heterospecific calls: two that elicited recognition from females in previous studies and three that did not. This study shows that females perceive variation in allopatric mating signals in acontinuous manner with no evidence of perceptual category formation. The strength of recognition is predicted by how different the target stimulus is from the conspecific call within a series of calls. But the differences in recognition responses among call series are not predicted by the similarity of the call series to the conspecific call. The latter result suggests that the strength of recognition of allopatric signals might be influenced by processes of stimulus generalization and past evolutionary history.

Acoustic Stimulation↗

The stress response in critical illness.

Under normal, unstressed conditions, the body maintains a dynamic equilibrium known as homeostasis--a complex interplay balancing the conflicting demands presented by many internal and external forces. In the face of threatened or actual disruptions (i.e., stress), molecular, cellular, physiologic, and behavioral responses act to restore homeostasis. These responses can be specific to a particular stressor and relatively circumscribed (e.g., secretion of insulin in response to an increase in blood glucose), or can be generalized and relatively nonspecific (e.g., behavioral manifestations of severe anxiety). Typically, more nonspecific and generalized responses occur in the setting of severe and threatening disruptions in homeostasis, and taken together, these responses are known as the "general adaptation or stress syndrome". We will describe the elements and organization of the generalized stress response with particular attention to the hypothalamic-pituitary-adrenal axis as it interacts with the immune system, and we will review what is known about this interactive network in the setting of critical illness.

Animals↗

Assessing pain responses during general anesthesia.

Major technical and pharmacological achievements in recent years have greatly influenced the practice of anesthesia. Clinical signs related to the main aspects of anesthesia, i.e., hypnosis, analgesia, and muscular relaxation, are increasingly obtainable from variables supplied by the monitoring equipment. It is not known, however, to what extent more indirect, patient-associated clinical signs of pain/depth of anesthesia are still considered of importance and relied on in the intraoperative management of surgical patients. The aims of the present study were to assess what clinical signs, indirect as well as monitor-derived, are considered indicative of intraoperative pain or depth of anesthesia by nurse anesthetists during general anesthesia. In connection with anesthetic management of surgical patients, Swedish nurse anesthetists (N = 40) were interviewed about clinical signs that they routinely assessed and were asked if the observed signs were considered indicative mainly of intraoperative pain or depth of anesthesia. It was found that skin-associated responses (temperature, color, moisture/stickiness) were commonly considered to indicate intraoperative pain rather than depth of anesthesia. Respiratory movements, eye reactions, and circulatory responses were considered to be indicative of either pain or insufficient depth of anesthesia. The present data indicate that indirect physiological signs are still considered of major importance by anesthesia nurses during the anesthetic management of surgical patients.

Anesthesia, General↗

Human B lymphocyte colony responses. I. General characteristics and modulation by monocytes.

The present study investigated the ability of human B cell-enriched subpopulations to focally proliferate and form colonies in semisolid cultures after stimulation with staph protein A (SpA). After 6 days of incubation, cultures of B-enriched populations exhibited distinct colonies, the number being dependent on the concentration of SpA and the cell density. Optimal colony responses were 1.6 x 10(3) per 1 x 10(6) B lymphocytes, and greater than 83% of the colony-forming cells expressed surface immunoglobulin (sIg). The depletion of adherent monocytes from the B cell-enriched preparations decreased the colony responses approximately 3-fold compared with the nondepleted B cell populations. Adding optimal numbers of adherent monocytes to the monocyte-depleted B cells restored the colony responses; however, less augmentation was observed in single-layer co-cultures containing greater than optimal numbers of monocytes. Identical experiments in double-layer semisolid cultures revealed that relatively greater numbers of monocytes were required to enhance B cell colony responses. Thus, progressively higher ratios of monocytes to B cells resulted in increasing numbers of colonies and failed to demonstrate the diminished colony responses observed in the single-layer system. These studies demonstrate that human B cells form distinct colonies when activated by SpA and that normal adherent monocytes modulate the magnitude of colony responses. Although monocytes predominately enhance B cell clonal differentiation, the evidence presented also suggests that, to a lesser extent, soluble inhibitory materials are elaborated.

B-Lymphocytes↗