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Enhanced glycemic responsiveness to epinephrine in insulin-dependent diabetes mellitus is the result of the inability to secrete insulin. Augmented insulin secretion normally limits the glycemic, but not the lipolytic or ketogenic, response to epinephrine in humans.

To determine if the enhanced glycemic response to epinephrine in patients with insulin-dependent diabetes mellitus (IDDM) is the result of increased adrenergic sensitivity per se, increased glucagon secretion, decreased insulin secretion, or a combination of these, plasma epinephrine concentration-response curves were determined in insulin-infused (initially euglycemic) patients with IDDM and nondiabetic subjects on two occasions: once when insulin and glucagon were free to change (control study), and again when insulin and glucagon were held constant (islet clamp study). During the control study, plasma C-peptide doubled, and glucagon did not change in the nondiabetic subjects, whereas plasma C-peptide did not change but glucagon increased in the patients. The patients with IDDM exhibited threefold greater increments in plasma glucose, largely the result of greater increments in glucose production. This enhanced glycemic response was apparent with 30-min increments in epinephrine to plasma concentrations as low as 100-200 pg/ml, levels that occur commonly under physiologic conditions. During the islet clamp study (somatostatin infusion with insulin and glucagon replacement at fixed rates), the heightened glycemic response was unaltered in the patients with IDDM, but the nondiabetic subjects exhibited an enhanced glycemic response to epinephrine indistinguishable from that of patients with IDDM. In contrast, the FFA, glycerol, and beta-hydroxybutyrate responses were unaltered. Thus, we conclude the following: Short, physiologic increments in plasma epinephrine cause greater increments in plasma glucose in patients with IDDM than in nondiabetic subjects, a finding likely to be relevant to glycemic control during the daily lives of such patients as well as during the stress of intercurrent illness. Enhanced glycemic responsiveness of patients with IDDM to epinephrine is not the result of increased sensitivity of adrenergic receptor-effector mechanisms per se nor of their increased glucagon secretory response; rather, it is the result of their inability to augment insulin secretion. Augmented insulin secretion, albeit restrained, normally limits the glycemic response, but not the lipolytic or ketogenic responses, to epinephrine in humans.

Adult↗

Molecular characterization and differential expression of cytokinin-responsive type-A response regulators in rice (Oryza sativa).

BACKGROUND: The response regulators represent the elements of bacterial two-component system and have been characterized from dicot plants like Arabidopsis but little information is available on the monocots, including the cereal crops. The aim of this study was to characterize type-A response regulator genes from rice, and to investigate their expression in various organs as well as in response to different hormones, including cytokinin, and environmental stimuli. RESULTS: By analysis of the whole genome sequence of rice, we have identified ten genes encoding type-A response regulators based upon their high sequence identity within the receiver domain. The exon-intron organization, intron-phasing as well as chromosomal location of all the RT-PCR amplified rice (Oryza sativa) response regulator (OsRR) genes have been analyzed. The transcripts of OsRR genes could be detected by real-time PCR in all organs of the light- and dark-grown rice seedlings/plants, although there were quantitative differences. The steady-state transcript levels of most of the OsRR genes increased rapidly (within 15 min) on exogenous cytokinin application even in the presence of cycloheximide. Moreover, the expression of the OsRR6 gene was enhanced in rice seedlings exposed to salinity, dehydration and low temperature stress. CONCLUSION: Ten type-A response regulator genes identified in rice, the model monocot plant, show overlapping/differential expression patterns in various organs and in response to light. The induction of OsRR genes by cytokinin even in the absence of de novo protein synthesis qualifies them to be primary cytokinin response genes. The induction of OsRR6 in response to different environmental stimuli indicates its role in cross-talk between abiotic stress and cytokinin signaling. These results provide a foundation for further investigations on specific as well as overlapping cellular functions of type-A response regulators in rice.

Amino Acid Sequence↗

Mechanisms of pulse response and differential response of bacteriorhodopsin and their relations.

Bacteriorhodopsin (BR) films are oriented and deposited on indium tin oxide conductive glass by using electrophoretic sedimentation and Langmuir-Blodgett methods to construct sandwich-type photocells, respectively. The pulse response photoelectric signal of the BR photocell under pulsed laser and the differential response photoelectric signal under irradiation of interval light are measured. The origins of these two types of photoelectric responses and their correlations are analyzed. The pulse response signal initiates from the ultrafast charge separation of the retinal and the proton translocation followed by the deprotonation and reprotonation of the Schiff base and its surrounding amino acids. This is a quick response and is the preceding reaction of the differential response. The differential response signal is caused by the charging and discharging of the continuous proton current of the BR light-driven proton pump at light-on and light-off, which is a slow process. The differential response is related to not only the construction of the BR photocell but also the coupling mode of measurement. To observe the differential response signal, the BR photocell must have large enough B3 and B3' components in its pulse response as well as an alternative coupling mode to measure it.

Bacteriorhodopsins↗

Discrimination of response-reinforcer and response-stimulus contingencies in pigeons.

For three pigeons (Experiment 1), the presentation of a red response key ended with a food presentation either following two responses separated by at least 10 seconds (a DRL contingency) or following a 10-second response-free period (a DRO contingency). For three other birds (Experiment 2), a brief stimulus presentation terminated the DRL and DRO contingencies. A white side key was presented next and ended with response-dependent food following one contingency and a timeout following the other. Since the contingency on the red key was unsignaled, differential responding on the white side key could indicate that the two response-reinforcer relations had been discriminated. In Experiment 1, the red-key duration and number of responses influenced white-key responding following the contingency that predicted the timeout. A response-initiated DRO was instated, and the influence of red-key duration and response number on white-key responding was diminished. In both experiments, the 10-second time criterion in both contingencies was varied from 0.34 second to 10 seconds. Even at short time intervals the DRO and DRL contingencies were readily discriminated. Pigeons tended to class the two contingencies according to a rule that did not involve simply stimulus duration, numbers of responses, or even the time between a response and its consequence.

Animals↗

The operant conditioning of response variability: Free-operant versus discrete-response procedures.

The operant conditioning of response variability under free-operant and discrete-response procedures was investigated. Two pigeons received food only if their pattern of four pecks on two response keys differed from the patterns emitted on the two immediately preceding trials. Under the free-operant procedure, the keys remained illuminated and operative throughout each trial. There was little variability in the response patterns that resulted, and the pigeons received fewer than one third of the available reinforcers. Under the discrete-response procedure, a brief timeout period followed each response. Variability increased under this procedure, and the pigeons obtained three fourths of the available reinforcers. Previous successes and failures to produce response variability may have been due to the use or failure to use, respectively, a discrete-response procedure. Respondent effects inherent in the free-operant procedure may encourage the development of response stereotypy and, in turn, prevent the development of response variability.

Journal Article↗

The effects of diazepam and triazolam on repeated acquisition and performance of response sequences with an observing response.

Drugs often disrupt the acquisition of new response sequences at doses that fail to disrupt the performance of a previously acquired response sequence. This selective drug effect may result from differences in the control exerted by the stimuli presented after each response in the acquisition and performance sequences. To examine the function of these stimuli, an observing procedure was incorporated into a multiple schedule of repeated acquisition and performance of response sequences, in which stimulus presentations were contingent upon an observing response. Three experiments were conducted with humans. Experiment 1 compared responding with and without the observing contingency. No difference was found in the overall percentage of errors across the two conditions. Within the observing condition, observing behaviour was maintained in the acquisition component as long as errors occurred, but was not maintained in the performance component. Experiment 2 examined whether a contingency that increased errors also would increase observing in both the acquisition and performance components. Specifically, reinforcer delivery in each component was contingent upon emitting 10 correct responses and one, two, or four errors. Observing responses increased in the acquisition component as the error requirement increased, whereas observing responses in the performance component increased only when the error requirement was four. Experiment 3 assessed the effects of diazepam (0, 7.5, 15, and 30 mg/70 kg, p.o.) and triazolam (0, 0.375, and 0.75 mg/70 kg, p.o.) on repeated acquisition and performance baselines with the observing contingency. Selective drug effects were obtained in this modified procedure; that is, the percentage of errors in the acquisition component increased at doses that failed to affect the percentage of errors in the performance components. Importantly, drug effects were selective, even though observing responses were not emitted in the performance component and, hence, the stimulus presentations did not occur in that component. These findings suggest that alternative explanations for these differential effects are needed; in that regard, a response-unit account of the selective drug effects is discussed.

Adult↗

Effect of drugs on response-duration differentiation VII: response-force requirements.

Rats were trained to press a lever for at least 1 s but for less than 1.3 s. The force required to press the lever was then increased or decreased by 10, 15, or 20 g. Increases in the force requirements for lever pressing decreased timing accuracy, but decreases in the force requirement had the opposite effect. Accuracy decreases at increasing force requirements were characterized by an increase in the relative frequency of responses that were too short to meet the reinforcement criterion. In contrast, increases in accuracy when the force requirements were decreased were characterized by increases in response durations that met the reinforcement criterion and decreases in the relative frequency of responses that were too short to produce the reinforcer. Phencyclidine (PCP) and methamphetamine produced dose-dependent decreases in accuracy that were associated primarily with increases in the relative frequency of short response durations, although methamphetamine also produced increases in long response durations at some doses. When the effects of PCP were determined with the force requirement increased by 10 g or decreased by 15 g, the cumulative response-duration distribution shifted toward even shorter response durations. When the effects of methamphetamine were determined with the force requirement on the lever increased by 10 g, the cumulative frequency distribution was shifted toward shorter response durations to about the same extent as it had been before force requirements increased; however, when the force required to press the lever was decreased by 15 g, these shifts toward shorter response durations almost completely disappeared. These results show that increases and decreases in the force requirements for lever pressing have different effects on the accuracy of temporal response differentiation.

Animals↗

Auditory brainstem responses of the cat: on- and off-responses.

The auditory brainstem on- and off-responses evoked by tone and noise bursts have been studied in the cat. The number and amplitude of the off-response waves are proportional to the frequency specificity of the on-response, being greatest for the 4-kHz tone burst and smallest for the noise burst. The threshold of the 0.5-kHz off-response is lower than that of the on-response, but the amplitude of the former does not increase at higher stimulus levels. Derived-band studies show that at 4 kHz the on-and off-responses have identical frequency content, the 0.5-kHz off-response is restricted to the 2- to 8-kHz frequency band, while the noise burst off-response is entirely high frequency. The off-response is an on-response and is evoked by acoustic transients from the loudspeaker transducer.

Acoustic Stimulation↗

Reduction in aortic smooth muscle beta-adrenergic responsiveness results in enhanced norepinephrine responsiveness in the Dahl salt-sensitive rat.

In an earlier report we observed alterations in aortic smooth muscle alpha- and beta-adrenergic responsiveness in the Dahl rat. The present study was designed to define the time course of these changes and further characterize the alterations in this model of hypertension. Four-week-old male Dahl salt-sensitive (DS) rats were placed on either a normal (DSN) or high salt diet (8% NaCl; DSH). Aortic smooth muscle responsiveness was studied at 3 and 6 weeks of the dietary treatment. No differences were seen between the 2 groups in either the contractile response to KCl or the relaxation responses to sodium nitrite and acetylcholine. Isoproterenol-induced relaxation was significantly attenuated and contractile response to norepinephrine (NE) were enhanced at 3 weeks of treatment in DSH rats, however, no differences were seen between the 2 groups at 6 weeks. Since alterations were seen only at 3 weeks of treatment, aortic smooth muscle responsiveness to the specific alpha-agonists phenylephrine (alpha 1), guanfacine (alpha 2) and contractile responses to NE in the presence of propranolol were evaluated at three weeks. No differences were observed between the 2 groups with any of these treatments. Thus, it appears that the increased NE responsiveness seen in aortic smooth muscle of DSH rats during the developmental stage of the hypertension is the result of a decrease in beta-adrenergic responsiveness and not an increase in alpha-adrenergic responsiveness.

Animals↗

Response-response compatibility during bimanual movements: evidence for the conceptual coding of action.

The present study investigated response-response (R-R) compatibility in a bimanual keypressing task. Numeric and spatial stimuli were used to cue responses for each hand. Two groups of participants differed in terms of the stimulus-response mappings for the numeric stimuli. For one group, the numeric stimuli were mapped so that the same number for each hand indicated responses that were anatomically compatible (e.g., index finger of both hands). For the other group, the same number for each hand indicated responses that were left-right compatible (e.g., leftmost finger of both hands). The spatial stimuli were mapped in a spatially compatible manner to the responses for both groups. For numeric stimuli, reaction times (RTs) were faster when the same number indicated the response for each hand, regardless of the mapping. For the spatial stimuli, RTs were determined not only by the pairing of stimuli or responses, but also by how the responses were indicated by numeric stimuli. The results indicate that R-R compatibility effects are mediated by abstract codes that reflect individuals' conceptualizations of their actions.

Adolescent↗

Prevention of allergen-specific, Th2-biased immune responses in vivo: role of increased IL-12 and IL-18 responsiveness.

The factors that control development of adaptive responses to exogenous Ag remain incompletely understood. An ability to selectively direct immunity toward a specific phenotype would be of clinical benefit in numerous immunological disorders. Administration of chemically modified allergen glutaraldehyde-polymerized OVA (OA-POL) leads to >90% reductions in murine IgE and >500-fold increases in IgG2c responses that develop upon subsequent immunization with native Ag. In the present study, we examine the mechanisms underlying this reorientation of the type 2 dominant response that would normally develop. Lack of endogenous IL-12 or IFN-gamma results in markedly reduced induction of IgG2c responses following OA-POL treatment, but only IFN-gamma(-/-) mice demonstrate reduced capacity to prevent IgE induction. This indicates that while both IL-12 and IFN-gamma are critical promoters of type 1 immunity, only IFN-gamma is required to maximally inhibit development of type 2 immune responses. Compared with OVA-immunized mice, CD69(+) T cells from OA-POL-immunized mice demonstrate elevated IL-12Rbeta(2), IL-18Ralpha, and IL-18Rbeta mRNA levels, as well as increased IFN-gamma production in response to rIL-12 or rIL-18 stimulation. Collectively, these data indicate that preventing induction of type 2 immune responses is critically dependent on altered T cell responsiveness to these cytokines. The finding that targeted, Ag-specific manipulation of IL-12 and IL-18 responsiveness can be used to shape the phenotype of the dominant immune response that develops suggests that specifically targeting IL-12 and IL-18 receptor expression may offer clinical options for clinical prophylaxis or intervention.

Allergens↗

Adjuvant action of capsular polysaccharide of Klebsiella pneumoniae on antibody response. IV. The roles of antigen and adjuvant for induction of primary and secondary antibody responses and for development of immunological memory to bovine serum albumin.

A study was performed to clarify the roles of primary and secondary injections of antigen and adjuvant (capsular polysaccharide of Klebsiella pneumoniae, CPS-K) in induction of antibody responses and in the development of immunological memory in mice to bovine serum albumin (BSA). A primary injection of BSA alone neither induced significant primary antibody response nor increased immunological memory for a secondary antibody response but, if primary injections of BSA and CPS-K were performed simultaneously, high antibody responses were induced. Moreover, a prior injection of BSA alone or CPS-K alone decreased the level of primary antibody response and the degree of increase in memory following the subsequent injection of BSA mixed with CPS-K. In contrast, a secondary injection of BSA alone into mice once primed with a mixture of BSA and CPS-K elicited very high secondary type antibody response and increased secondarily the memory for a tertiary antibody response. Injection of CPS-K simultaneously with or shortly before or after the secondary injection of BSA did not increase the level of the secondary antibody response and the degree of the secondary increase in memory. Augmentation of the secondary antibody response was elicited by simultaneous injection of CPS-K only when the secondary response was induced inadequately by a suboptimum or supraoptimum dose of antigen.

Adjuvants, Immunologic↗

Lipopolysaccharide responsiveness is an important factor in the generation of optimal antigen-specific T cell responses during infection with gram-negative bacteria.

We previously have found that the endotoxin (LPS) of Gram-negative bacteria is a major determinant of macrophage Ia induction during infection with these organisms. Specifically, i.p. injection of Gram-negative bacteria elicits a striking macrophage Ia response in LPS-responder mice but virtually no response in LPS-low-responder mice. As an extension of these findings, in this report we have tested the hypothesis that the inability of LPS-low responder mice to mount an Ia response during Gram-negative infection may in turn impair their capacity for generation of appropriate antibacterial T cell responses. Our results demonstrate that for a variety Gram-negative organisms (Salmonella typhimurium, Salmonella minnesota, and Escherichia coli), both macrophage Ia induction and the generation of Ag-specific T cell responses are controlled by the lps gene. We also have asked whether the expression of additional toxins (other than LPS) by infecting Gram-negative organisms can "override" this lps gene control of macrophage and T cell responses. We have found that infection of LPS-low-responder mice with an E. coli strain that expresses a hemolytic exotoxin (Hly) leads to the induction of macrophage Ia expression as well as the generation of T cell responses to both the Hly molecule and to other E. coli-associated Ag, whereas no responses are generated during infection with a Hly- strain. This result suggests that LPS-low responder mice have no inherent defect in T cell responsiveness to Gram-negative bacterial Ag but rather that these mice fail to receive an LPS-mediated signal required for the induction of Ia expression and subsequent generation of peritoneal T cell immunity. These findings, when taken together with results presented in the accompanying paper, strengthen the argument that bacterial toxin production (and the ability of the host to respond to the toxin) can represent a critical determinant of the induction of macrophage Ia expression and in turn, of Ag-specific T cell responses during bacterial infection.

Animals↗

[Suggestion to physiological role of the frog tongue off-response to continuous tactile stimulation, from the viewpoint of the response figures].

The responses of the bullfrog lingual surface to continuous tactile flow stimulation for 3 minutes were characterized by a presence of conspicuous off-response. At that time the on-responses of the lingual surface were uniform in shape. The off-responses in the same situation were not uniform but multiform against expectation. These multiform off-responses could be roughly classified into two groups; one was high slender triangular shape resembling phasic response and slightly static response, and the other was low isosceles or ladder shape. The difference of the shape probably indicates the difference in the time series of centripetal input signalling. The tactile off-response on the whole tongue surface could be reconstructed by summing up the off-response on the lingual apex region and that of the radix region. This was one possibility to explain the multiform lingual tactile off-response pattern.

Animals↗

Intramural nerve-mediated inotropic responses of left atria of rats and guinea pigs: demonstration of alpha adrenergic and nonadrenergic noncholinergic responses in guinea pigs.

The effects of transmural nerve stimulation (TNS) on contractile responses of rat and guinea pig atria were analyzed pharmacologically. Isolated left atria were electrically driven through AgAgCl field electrodes and TNS was performed by brief introduction of defined stimulation patterns through the same electrodes. Step elevations in stimulating voltage induced biphasic inotropic responses in the left atria of both species: an initial negative component which was usually overwhelmed by a subsequent positive one. The transient negative inotropic response was induced by parasympathetic cholinergic nerve excitation, inasmuch as it was abolished by atropine. In the left atrium of the rat, the TNS-induced positive inotropic response was due exclusively to adrenergic nerve excitation through activation of beta-1 adrenoceptors. In contrast, analysis of the time course of responses in guinea pig left atria after nerve stimulation at 10 Hz revealed a positive inotropic response consisting of two phases; rapid and delayed phases were superimposed upon each other. The rapid phase was reduced by atenolol, a beta-1 antagonist, and attenuated further by prazosin, an alpha-1 antagonist. In the presence of both atenolol and prazosin, TNS of guinea pig left atria still induced a positive inotropic response but it had a slow onset and decay. This is termed the delayed phase response. TNS induced a similar delayed inotropic response in atria from surgically sympathectomized or reserpine-pretreated guinea pigs, from which catecholamine-fluorescence nerves and responses to tyramine were absent. These results demonstrate that TNS excitated adrenergic, cholinergic and nonadrenergic noncholinergic nerves in guinea pig left atria.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Cytotoxic T lymphocyte response to minor H-43a alloantigen in H-43b mice. Privileged H-2Kb restriction to the response is not due to immunodominance or epistatic effect but due to Ir gene function of H-2Kb itself.

Previous study demonstrated that anti-H-43a cytotoxic T lymphocyte (CTL) response of H-43b CWB (H-2b) stain carrying non-major histocompatability complex (MHC) genes of C3H and F1 strains raised by crossing CWB with various H-43b strains was restricted exclusively by self H-2Kb (Kb). In the present study, newly produced C3W strain (H-2k, H-43b), which is H-43-congenic to C3H/HeN (H-2k, H-43a), was used as H-43b mice, and possibility of immunodominance of Kb was examined. No anti-H-43a CTL response could be induced in C3W strain and F1 strains raised by crossing C3W with other H-43b strains not carrying Kb. Thus, the possibility of immunodominance of Kb over the other MHC class I alleles could not be supported. We also examined possibility of epistatic effect of I region genes and non-MHC genes on the Kb restriction. (C3W x C57BL/6)F1(I-Ak/b) and (C3W x B6.CH-2bm12)F1(I-Ak/bm12)mice showed equally anti-H-43a CTL response restricted exclusively by self Kb, and (C3W x B10.MBR)F1(Ik/k) mice also showed anti-H-43a CTL response restricted solely by self Kb. Cold target competition experiments demonstrated that H-43b C57BL/10 or A.BY mice, which do not have non-MHC genes of C3H mounted anti-H-43a CTL response restricted solely by self Kb. Thus, no relation of I region genes or non-MHC genes to the Kb restriction was shown. All the results indicate that H-43b mouse strains, including F1, can not achieve anti-H-43a CTL response unless they carry Kb allele. Notably, (C3W x C57BL/6)F1 mice mounted self Kb-restricted anti-H-43a CTL response, whereas (C3W x B6.CH-2bm1)F1 mice carrying mutated Kb could not mount anti-H-43a CTL response at all. These findings indicate strongly that Kb itself is classical Ir gene of anti-H-43a CTL response and directs self Kb restriction of the response.

Animals↗

Limitations of thermodilution ejection fraction: degradation of frequency response by catheter mounting of fast-response thermistors.

The present study examined whether catheter-mounting of a fast-response thermistor impaired the thermistor's ability to measure rapid temperature changes during thermodilution measurement of ejection fraction (EF). The response to a square-wave temperature change of six fast-response thermistors mounted on commercially available, pulmonary artery balloon-flotation catheters was compared to the response of a similar but unmounted fast-response thermistor. The response of the catheter-mounted fast-response thermistors recorded only 82% to 92% of a step-temperature change at 0.5 sec, and 88% to 96% of the step change at 1.0 sec. In contrast, the unmounted fast-response thermistor responded to 100% of the step change in 125 msec. The response of the catheter-mounted fast-response thermistors demonstrated an important slow component (second time constant) introduced by the catheter body, so that equilibration to a temperature change was not complete for about 6 sec. This slow equilibration lowered EF measured by thermodilution below true EF.

Cardiac Output↗

Ageing and immunity in outbred NMRI mice: lack of correlation between age-related decline of the response to T cell mitogens, the antibody response to a T-dependent antigen and lifespan in outbred NMRI mice.

Responses to different mitogens and the primary in vitro antibody response to a T-dependent antigen (SRBC) were tested in individual mice of various ages from an outbred strain (NMRI). Comparing mean values, an age-related decrease was found only for the responses to Con A and PHA but not for LPS nor for the primary in vitro antibody response to SRBC. The magnitude of the responses obtained in individual mice of the same age varied greatly. Some of the young as well as aged animals could respond very well to antigen, mitogen or both and there was a complete lack of correlation between the magnitude of individual responses to mitogen and the number of PFC produced in the in vitro antibody response to SRBC. Additionally, we investigated whether the magnitude of the immune responses measured in individual mice had any influence on their lifespan. The mitogen response and the in vitro PFC production of spleen cells from individual semi-splenectomized mice were therefore compared with their lifespan. The lifespan did not appear to be influenced by any of the immune responses measured.

Aging↗