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PubMed1992

Airway response to electrical field stimulation in sensitized inbred mice. Passive transfer of increased responsiveness with peribronchial lymph nodes.

We have examined the effects of repeated exposure to antigen on airway responses to cholinergic stimulation in two inbred strains of mice that are similar in underlying cholinergic airway responsiveness, yet differ in their ability to produce IgE. Both BALB/c and SJL/J mice were repeatedly exposed to ovalbumin by inhalation for a 10-d period. While the BALB/c mice developed IgE antibody to this allergen, the SJL/J strain failed to mount an appreciable IgE response. In vitro assessments of the response of tracheal smooth muscle from saline exposed mice (controls) of both strains demonstrated responses to both methacholine and electrical field stimulation that were not significantly different between the strains. Following exposure to ovalbumin, the BALB/c strain developed a significant increase in their response to electrical field stimulation, while their response to methacholine was unaltered. In contrast, the in vitro responsiveness to these stimuli did not increase in SJL/J mice following similar exposure to inhaled nebulized ovalbumin. The passive transfer of cells from the peribronchial lymph nodes of ovalbumin-sensitized BALB/c mice into syngeneic nonimmune mice also led to increases in responsiveness of tracheal smooth muscle to electrical field stimulation. In contrast, transfer of cells from nonsensitized mice did not alter responsiveness. These results suggest that murine species capable of developing an IgE response to allergen also develop alterations in the neural control of their airways. Further, this alteration appears to be lymphocyte dependent, in that cells found within peribronchial lymph nodes following allergen exposure are capable of transferring this increase in responsiveness to nonimmune mice.

Animals↗
PubMed2000

Effects of acute tryptophan depletion on prepulse inhibition of the acoustic startle (eyeblink) response and the N1/P2 auditory evoked response in man.

Contraction of the orbicularis oculi muscle in response to a sudden loud sound (acoustic startle response) and the N1/P2 component of the auditory evoked potential are both attenuated when a brief low-intensity stimulus is presented 30-500 ms before the 'startle-eliciting' stimulus (prepulse inhibition). Here, we report the effect of acute tryptophan depletion on prepulse inhibition of these responses. Thirteen males (21-52 years) participated in two sessions separated by 7 days, in which they ingested a drink containing a mixture of amino-acids, which either included (+ TP) or did not include (- TP) tryptophan, according to a balanced double-blind design. Electromyographic (EMG) responses of the orbicularis oculi muscle and N1/P2 auditory evoked potentials were recorded in a 20-min session, 6 h after ingestion of the mixture. Subjects received 40 trials in which 1-kHz sounds were presented: (i) 40 ms, 115 dB ('pulse alone' trials) and (ii) 40 ms, 85 dB, followed after 120 ms by 40 ms, 115 dB ('prepulse/pulse' trials). Mean amplitudes of the EMG response and the N1/P2 potential were derived from the pulse-alone trials and, in each case, percentage prepulse inhibition was calculated. Plasma tryptophan levels were measured from blood samples taken before and 7 h after each treatment. Under the + TP condition, both the EMG response and the N1/P2 complex showed > 60% prepulse inhibition. The - TP condition was associated with (i) significant suppression of prepulse inhibition of the EMG response, with no significant change in response amplitude and (ii) reduction of the amplitude of the N1/P2 potential, with no significant change in prepulse inhibition of this response. Tryptophan levels rose by 90+/-15% under the + TP condition and fell by 81+/-3% under the - TP condition. The suppression of prepulse inhibition of the acoustic startle response under the - TP condition suggests that central 5-hydroxytryptaminergic mechanisms may be involved in regulating prepulse inhibition of this response. The lack of effect of tryptophan depletion on prepulse inhibition of the N1/P2 potential suggests that different mechanisms are involved in prepulse inhibition of the startle response and the N1/P2 complex.

Acoustic Stimulation↗
PubMed2003

Estrogen receptor-dependent genomic responses in the uterus mirror the biphasic physiological response to estrogen.

The physiological responses of the rodent uterus to acute estrogen (E) dosing can be divided into early and late events. Examples of early responses include increased RNA transcription, hyperemia, and water imbibition 2 and 6 h following E administration respectively, whereas later responses include cycles of DNA synthesis and mitosis of epithelial cells beginning 10 and 16 h after E. The development of estrogen receptor (ER) knockout (ERKO) mice, combined with microarray technology, has allowed us to design a genomic approach to study the acute response of the rodent reproductive tract to E. To determine whether early and late biological responses are correlated with altered regulation of a single set of genes or distinct sets of genes characteristic of early and late responses, uterine RNA was obtained from ovariectomized mice that were treated with vehicle or with estradiol for 2 h (early) or 24 h (late). Samples were also prepared from identically treated mice that lacked either ERalpha (alphaERKO) or ERbeta (betaERKO) to address the relative contributions of the ERs in the uterine responses. Microarray analysis of the relative expression of 8700 mouse cDNAs indicated distinct clusters of genes that were regulated both positively and negatively by E in the early or late phases as well as clusters of genes regulated at both times. Both early and late responses by the betaERKO samples were indistinguishable from those of WT samples, whereas the alphaERKO showed little change in gene expression in response to E, indicating the predominant role for ERalpha in the genomic response. Further studies indicated that the genomic responses in samples from intermediate time points (6 h, 12 h) fall within the early or late clusters, rather than showing unique clusters regulated in the intermediary period. The use of this genomic approach has illustrated how physiological responses are reflected in genomic patterns. Furthermore, the identification of functional gene families that are regulated by E in the uterus combined with the utilization of genetically altered experimental animal models can help to uncover and define novel mechanisms of E action.

Animals↗
PubMed2001

Partial response activation to masked primes is not dependent on response readiness.

Masked primes presented foveally prior to a target trigger an initial partial activation of their corresponding response, followed by an inhibition of the same response. The latter phase results in performance costs on compatible trials and performance benefits on incompatible trials relative to neutral trials (negative compatibility effect). The present study investigated whether this activation-follow-by-inhibition process depends on the overall or specific state of response readiness. In two masked priming experiments, response readiness was manipulated by varying the relative frequency of Go-trials in a Go/NoGo task (Exp. 1) and the relative frequency of left- and right-hand responses in a 2-alternative choice reaction time task (Exp. 2). In both experiments, mean reaction times were longer for infrequent responses than for frequent responses. However, negative compatibility effects were not affected by response frequency. This result indicates that neither the general ability of masked primes to elicit a partial motor activation nor the specific time course of this process is dependent on response readiness. It is concluded that response readiness affects the execution of an overt response rather than the initial activation of this response.

Adult↗
PubMed2002

Stimulus-response compatibility and psychological refractory period effects: implications for response selection.

The purpose of this paper was to provide insight into the nature of response selection by reviewing the literature on stimulus-response compatibility (SRC) effects and the psychological refractory period (PRP) effect individually and jointly. The empirical findings and theoretical explanations of SRC effects that have been studied within a single-task context suggest that there are two response-selection routes-automatic activation and intentional translation. In contrast, all major PRP models reviewed in this paper have treated response selection as a single processing stage. In particular, the response-selection bottleneck (RSB) model assumes that the processing of Task 1 and Task 2 comprises two separate streams and that the PRP effect is due to a bottleneck located at response selection. Yet, considerable evidence from studies of SRC in the PRP paradigm shows that the processing of the two tasks is more interactive than is suggested by the RSB model and by most other models of the PRP effect. The major implication drawn from the studies of SRC effects in the PRP context is that response activation is a distinct process from final response selection. Response activation is based on both long-term and short-term task-defined S-R associations and occurs automatically and in parallel for the two tasks. The final response selection is an intentional act required even for highly compatible and practiced tasks and is restricted to processing one task at a time. Investigations of SRC effects and response-selection variables in dual-task contexts should be conducted more systematically because they provide significant insight into the nature of response-selection mechanisms.

Association Learning↗
PubMed1997

Response force is sensitive to the temporal uncertainty of response stimuli.

Three experiments examined whether temporal uncertainty about the delivery of a response stimulus affects response force in a simple reaction time (RT) situation. All experiments manipulated the foreperiod; that is, the interval between a warning signal and the response stimulus. In the constant condition, foreperiod length was kept constant over a block of trials but changed from block to block. In the variable condition, foreperiod length varied randomly from trial to trial. A visual warning and response stimulus were used in Experiment 1; response force decreased with foreperiod length in the variable condition, but increased in the constant condition. This result is consistent with the hypothesis that responses are less forceful when the temporal occurrence of the response stimulus is predictable. In a second experiment with an auditory warning signal and a response stimulus, response force was less sensitive to foreperiod manipulations. The third experiment manipulated both the modality and the intensity of the response signal and employed a tactile warning signal. This experiment indicated that neither the modality nor the intensity of the response signal affects the relation between response force and foreperiod length. An extension of Näätänen's (1971) motor-readiness model accounts for the main results.

Acoustic Stimulation↗
PubMed2006

Regulatory T cell responses develop in parallel to Th responses and control the magnitude and phenotype of the Th effector population.

Host survival during schistosomiasis requires the development of a tightly regulated and Th2-polarized immune response against parasite egg Ags. In this system, Th1 response suppression has been thought to be enforced through the production of IL-10 by Th2 cells and natural T regulatory (Treg) cells. By comparing Th responses in schistosome egg-injected mice that lack IL-10, IL-4, and/or Treg cells, we have been able to build a detailed picture of the relative contributions of Treg cells, Th2 cells, and IL-10 to regulation of the egg-induced response. Our data indicate that eggs induce a marked Treg cell response, evident as the extensive proliferation of Foxp3(+) cells that is proportionally as great as the response occurring within the Th compartment. Furthermore, we show that Treg cells prevent Th1 response development and limit the magnitude of the Th2 response. Although Treg cells are able to produce IL-10 after egg injection, we found no evidence for a role for IL-10 in Treg-mediated suppression of Th cell responses, nor did we find evidence for an inhibitory effect of Th2 cells on Th1 response development. Thus, the magnitude and phenotype of the egg-induced effector Th response are controlled by a parallel response within the Treg population.

Animals↗
PubMed1992

[Effects of chronotropic responsive cardiac pacing on ventilatory response to exercise in patients with bradycardia].

To identify the effect of chronotropic responsive cardiac pacing on ventilatory responses to exercise, 9 patients with chronotropic incompetence underwent paired cardiopulmonary exercise tests with fixed demand rates (AAI, VVI) and chronotropic responsive (AAIR, VVIR, DDD) pacing modes. Compared with fixed rate pacing, chronotropic responsive pacing increased peak oxygen uptake and delayed the attainment of the anaerobic threshold (AT) with a higher level of oxygen consumption (p < 0.01). Dyspnea was a major symptom that limited exercise time in 7 patients with fixed rate pacing, which was prominent with chronotropic responsive pacing. Ventilation (VE) and the ratio of ventilation to CO2 production (VE/VCO2) were consistently higher with fixed rate pacing during exercise. To compare the responses between the 2 pacing modes with the same work loads under aerobic conditions, we measured ventilatory variables one min prior to the AT as obtained with fixed rate pacing. When switching the pacing mode from fixed rate pacing to chronotropic responsive pacing, VE and VE/VCO2 decreased significantly from 22.0 +/- 7.8 to 19.8 +/- 6.8 l/min, and from 37.4 +/- 5.4 to 33.6 +/- 5.2, respectively. Tidal volume did not change, but respiratory frequency decreased more with chronotropic responsive pacing (p < 0.05). Although peak VE did not differ between the 2 pacing modes, VE/VCO2 decreased more with chronotropic responsive pacing (p < 0.01). Respiratory frequency decreased and tidal volume increased more with chronotropic responsive pacing (p < 0.05). This study suggests that chronotropic responsive cardiac pacing attenuates exertional dyspnea by improving ventilatory responses to exercise as well as increasing the cardiac output in patients with chronotropic incompetence.

Adult↗
PubMed1987

Characterization of vasopressor response to sympathetic stimulation in the pithed rat: differential regulation of neuronally stimulated and blood-borne catecholamine-stimulated pressor responses in rats harboring pheochromocytoma.

The vasopressor response to sympathetic stimulation in the pithed rat was characterized both by analyzing the effects of chemical sympathectomy, adrenalectomy and selective antagonists on the vasopressor response and by measurement of changes in plasma concentrations of catecholamines. Stimulation of the spinal sympathetic outflow evoked a biphasic pressor response: an initial transient component was caused mainly by postganglionic sympathetic nerve stimulation (the direct response); a slowly developing secondary component was mediated predominantly by circulating catecholamines released from the adrenal medulla (the adrenal response). Parallel analysis of plasma catecholamines showed that the rise in epinephrine appeared to be closely related to this adrenal component. The pressor response in adrenalectomized rats was selectively blocked by prazosin but not by yohimbine; however, in sympathectomized rats, the pressor response was abolished by prazosin and yohimbine together but not by either drug given alone. These results suggest that the direct, neurogenic component is mediated mainly by alpha-1 adrenoceptors whereas the secondary, adrenally mediated response occurs by activation of both alpha-1 and alpha-2 adrenoceptors. Furthermore, the in vivo regulation of each component of the pressor response was studied in rats harboring pheochromocytoma (PHEO), a tumor causing marked elevations in endogenous catecholamine concentrations. In PHEO rats, the direct pressor response was found to be relatively intact but the adrenal response was blunted. Inasmuch as there was normal rise in plasma epinephrine to electrical stimulation in PHEO rats, the results suggest a differential regulation of neuronally stimulated and blood-borne catecholamine-mediated pressor responses in PHEO rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1985

Muscarinic responses and binding in a murine neuroblastoma clone (N1E-115). Mediation of separate responses by high affinity and low affinity agonist-receptor conformations.

Murine neuroblastoma cells (clone N1E-115) possess muscarinic receptors that mediate multiple responses, including the elevation of cyclic GMP levels and the inhibition of receptor-mediated increases in cyclic AMP. Evidence is presented showing that two muscarinic agonist-receptor conformations in N1E-115 cells each separately mediate a cyclic nucleotide response. Pirenzepine inhibited the [3H]cyclic GMP response to carbachol with a KD value of approximately 6 nM, whereas it inhibited the ability of carbachol to reduce prostaglandin E1-mediated elevations in [3H]cyclic AMP levels with a KD value of 93 nM, thus differentiating between two classes of receptors involved in these responses. Ten muscarinic agonists were studied for their ability to mediate the two cyclic nucleotide responses. Six were as effective as acetylcholine in the reduction of [3H]cyclic AMP levels, but only two were as effective as acetylcholine in elevating [3H]cyclic GMP levels. Four agonists (arecoline, pilocarpine, oxotremorine, and McN-A343) were ineffective in increasing [3H]cyclic GMP levels. These four agonists and bethanecol, which could increase [3H]cyclic GMP levels only 18% as well as acetylcholine, behaved as competitive antagonists in this response to carbachol. These partial agonists, in contrast to carbachol, bound to only one class of muscarinic sites in N1E-115 cells with equilibrium dissociation constants determined by competition binding assays which agreed well with their respective EC50 values for their effect on [3H]cyclic AMP levels. The equilibrium dissociation constants for the partial agonists determined by their inhibition of carbachol in the [3H] cyclic GMP response also agreed well with their respective EC50 values for mediating the [3H]cyclic AMP response. Thus, the partial agonists bound to the same receptors at which carbachol mediated [3H]cyclic GMP formation, but with KD values about the same as their respective EC50 values for inhibition of prostaglandin E1-mediated [3H]cyclic AMP increases. The full agonists acetylcholine and methacholine, like carbachol, bound to two sites in N1E-115 cells. For the six agonists able to stimulate both responses at least to some degree, the ratio of their potencies at each response correlated with their respective efficacies at each response but with much more dependence in the [3H]cyclic GMP response.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

The lipopolysaccharide polyclonal response is a function of the background response.

The aims of this report are: to investigate the kinetics of the E. coli lipopolysaccharide polyclonal response as a function of the background response, to test the capacity of lipopolysaccharide to activate presumably resting memory cells for IgM. Because mice do not produce a plaque-forming cell background against rat erythrocytes, the mouse-rat erythrocyte system was chosen. Random bred Swiss albino mice, aged 2-3 months, were inoculated with rat erythrocytes (5 X 10(5)/mouse) and the course of the plaque response was followed up; no response was detected on day 0, it rose sharply up to day 4, dropped abruptly between days 4 and 7 and trailed off afterwards to disappear by day 29. As to the lipopolysaccharide-triggered anti-rat erythrocyte response, lipopolysaccharide (100 micrograms/mouse) was inoculated on days--3, 1, 4, 7, 18 and 29. post-rat erythrocytes and the responses were measured 3 days after lipopolysaccharide inoculation. The curve paralleled that of the antigenic response, although at a higher level; thus, both the specific and the polyclonal responses followed the same kinetics. At one month post-rat erythrocyte priming, the animals displayed a background comparable to that of naive mice, although their IgM response to a booster (2 X 10(7) erythrocytes, iv) was faster and greater (p less than 0.01) than the primary response to the same dose; i.e., there was IgM memory. Nevertheless, lipopolysaccharide stimulation (100 micrograms/mouse, ip) of primed animals gave a response comparable (p greater than 0.10) to that of naive mice; i.e., lipopolysaccharide alone was unable to elicit a secondary-like response.

Animals↗
PubMed1981

LPS regulation of the immune response: suppression of immune responses to orally administered T-independent antigen.

The regulation of immune responses to gastrically administered TI antigens has been investigated, and the characterization of a regulatory cell population has been performed. Intragastric administration of TNP-haptenated homologous erythrocytes (TNP-MRBC) induced splenic IgM anti-TNP PFC responses in LPS nonresponsive C3H/HeJ mice that were higher than those in LPS-responsive C3H/HeN mice and similar to those noted in athymic (nu/nu) C3H/HeN animals. The simultaneous intragastric administration of LPS with TNP-MRBC augmented immune responses in a manner similar to that previously reported for parenterally administered LPS and antigen. Further, LPS-induced augmentation of TNP-MRBC responses was greater in athymic mice. These findings were substantiated using in vitro spleen cultures. Intragastric challenge with a 2nd TI antigen, TNP-LPS, induced approximately 8-fold higher splenic anti-TNP PFC responses in athymic C3H/HeN mice compared with those in euthymic littermates. By admixture of B and T cell populations, it was demonstrated that the host responsiveness to TNP-LPS was negatively regulated by suppressor cells. Suppressive activity resided in a Thy 1.2-bearing, irradiation-resistant, nylon wool-nonadherent cell population. These cells could be demonstrated in spleen and Peyer's patches from young or old LPS-responsive C3H/HeN mice, but not in tissues from LPS nonresponsive C3H/HeJ mice. The specificity of the regulator cells was not limited to TNP-LPS responses, since immune responsiveness to another TI antigen, TNP-dextran, was also under the control of this cell population. These studies confirm the TI nature of TNP-MRBC and indicate that immune responses to gastrically administered antigens such as TNP-LPS, TNP-dextran, and possibly TNP-MRBC are negatively regulated by a suppressor T cell population. A role for endogenous LPS in the generation of regulator cells and the effect of these cells on host responses to gut-derived antigens is discussed.

Administration, Oral↗
PubMed1983

IgA responses in xid mice: oral antigen primes Peyer's patch cells for in vitro immune responses and secretory antibody production.

Because the gut-associated lymphoreticular tissue (GALT), e.g., Peyer's patches (PP), of X-linked immunodeficient (xid) mice possesses a subpopulation of mature B cells, we have characterized the ability of xid mice to respond to the thymic-dependent antigen sheep erythrocytes (SRBC) given by the oral route. Gastric intubation of SRBC to xid (CBA/N X DBA/2) F1 male or CBA/N mice, followed by the in vitro culture of dissociated PP cells with SRBC, resulted in IgM, IgG1, IgG2, and high IgA anti-SRBC plaque-forming cell (PFC) responses. The addition of unprimed PP but not splenic T cells to splenic xid B cell cultures resulted in IgM anti-SRBC PFC responses, suggesting the importance of GALT T cells for support of the immune responses to SRBC by splenic B cells from xid mice. Furthermore, purified PP T cells from SRBC orally primed xid mice supported in vitro IgA anti-SRBC PFC responses in B cell cultures from either the PP or the spleens of nonprimed xid mice. Higher IgA responses, however, occurred in PP, when compared with splenic B cell cultures. Additional evidence that the GALT of xid mice contains functional IgA precursor cells was provided by the finding that cloned H-2k PP T helper cells (PP Th A) supported IgA responses in PP B cell cultures derived from (CBA/N X C3H/HeN) F1 male (xid) mice. On the other hand, splenic B cells from these xid mice, in the presence of PP Th A cells, did not support in vitro responses. These results suggest that unique subpopulations of T cells occur in the GALT of xid and normal mice; one T cell subpopulation may induce immature B cells to become precursor IgA cells in the PP. A separate GALT T cell subpopulation, e.g., isotype-specific helper T cells, effectively collaborates with mature IgA B cells for the induction of IgA responses to orally administered antigen. When xid mice were gastric intubated with SRBC, followed by i.p. injection of SRBC, good splenic IgA anti-SRBC PFC responses were seen. Salivary and serum IgA antibodies were also detected in these xid mice. Nevertheless, the magnitude of the anti-SRBC response in xid mice was lower than that seen in similarly treated normal mice. These studies indicate that the GALT of both xid and normal mice possess unique populations of T cells that support in vitro responses in xid B cell cultures from either the spleen or the PP, which direct the mature B cell populations present toward IgA isotype-specific responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Neuronal responses of the rabbit cerebellum during acquisition and performance of a classically conditioned nictitating membrane-eyelid response.

Neuronal activity was recorded from regions of the cerebellar cortex and dentate-interpositus nuclei during learning and/or performance of a classically conditioned nictitating membrane (NM-a third eyelid)/eyeblink response in the rabbit. It was found that neurons located within restricted portions of the ansiform lobule and anterior lobe cortical regions and of the dentate-interpositus nuclei respond in relation to the performance of the learned eyeblink response. Furthermore, chronic recordings from the dentate-interpositus nuclei revealed that these responses develop in close relation to the learning of the conditioned eyeblink response. Stimulation of the dentate-interpositus nuclei through the recording electrodes in some cases yielded eyelid closure and NM extension in both trained and untrained animals. Lesion of the axons of the dentate-interpositus nuclei (superior cerebellar peduncle), a manipulation which is known to abolish the learned eyeblink response, abolished the stimulation effect. We have previously reported that lesions of the dentate-interpositus nuclei cause abolition of the learned eyeblink response. In the present study, we report that lesions of the regions of cerebellar cortex projecting to the dentate-interpositus nuclei do not permanently abolish the conditioned response, although the amplitude-time course of the learned response could be affected. These results, together with results of other studies, demonstrate that the medial dentate and/or lateral interpositus nuclei are active during learning and performance of the conditioned eyeblink response, are capable of producing this learned response, and are essential for the learning and retention of the conditioned eyeblink response. Therefore, the medial dentate and/or lateral interpositus nuclei are a part of the essential neuronal circuit involved in the learning and production of the classically conditioned eyeblink response in the rabbit.

Acoustic Stimulation↗
PubMed1977

Lymphocyte responses to purified ragweed allergens in vitro. I. Proliferative responses in normal, newborn, agammaglobulinemic, and atopic subjects.

To evaluate cell-mediated immune responsiveness to pollen allergens in atopic subjects, we studied the deoxyribonucleic acid (DNA) synthetic responses of their cultured lymphocytes to purified ragweek antigens E, K, and Ra-3. Since lymphocytes from some highly ragweed-sensitive subjects gave poor proliferative responses when harvested on day 6, we undertook a series of dose-response and time-course studies in atopic and control subjects. Surprisingly, vigorous DNA synthetic responses to antigen E occurred with lymphocytes from all 45 subjects, including 19 highly ragweed-sensitive atopic and control subjects. Surprisingly, vigorous DNA synthetic responses to antigen E occurred with lymphocytes from all 45 subjects, including 19 highly ragweed-sensitive atop adults (8 immunotherapy treated, 11 untreated); 13 nonatopic controls; 4 newborns, and 9 agammaglobulinemic patients. The geometric mean of peak response counts per minute in all 45 subjects was 21,163 and in unstimulated cultures was 2,416 (p = less than 0.0001). The mean day on which the maximal responses occurred was 8.7, and the mean dose eliciting the maximum responses was 59 mug/ml. Statistical comparisons of the stimulated culture data revealed no significant intergroup differences. The finding of vigorous responsiveness to these purified pollen allergens by lymphocytes from nonatopic normal, newborn, and agammaglobulinemic subjects suggests that ragweed pollen antigens are either ubiquitous and lead to cell-mediated responsiveness in all subjects with intact cell-mediated inmunity, or that they may have miogenic properties in addition to their known antigenic properties.

Adult↗
PubMed2002

DNA damage response pathway in radioadaptive response.

Radioadaptive response is a biological defense mechanism in which low-dose ionizing irradiation elicits cellular resistance to the genotoxic effects of subsequent irradiation. However, its molecular mechanism remains largely unknown. We previously demonstrated that the dose recognition and adaptive response could be mediated by a feedback signaling pathway involving protein kinase C (PKC), p38 mitogen activated protein kinase (p38MAPK) and phospholipase C (PLC). Further, to elucidate the downstream effector pathway, we studied the X-ray-induced adaptive response in cultured mouse and human cells with different genetic background relevant to the DNA damage response pathway, such as deficiencies in TP53, DNA-PKcs, ATM and FANCA genes. The results showed that p53 protein played a key role in the adaptive response while DNA-PKcs, ATM and FANCA were not responsible. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), mimicked the priming irradiation in that the inhibitor alone rendered the cells resistant against the induction of chromosome aberrations and apoptosis by the subsequent X-ray irradiation. The adaptive response, whether it was afforded by low-dose X-rays or wortmannin, occurred in parallel with the reduction of apoptotic cell death by challenging doses. The inhibitor of p38MAPK which blocks the adaptive response did not suppress apoptosis. These observations indicate that the adaptive response and apoptotic cell death constitute a complementary defense system via life-or-death decisions. The p53 has a pivotal role in channeling the radiation-induced DNA double-strand breaks (DSBs) into an adaptive legitimate repair pathway, where the signals are integrated into p53 by a circuitous PKC-p38MAPK-PLC damage sensing pathway, and hence turning off the signals to an alternative pathway to illegitimate repair and apoptosis. A possible molecular mechanism of adaptive response to low-dose ionizing irradiation has been discussed in relation to the repair of DSBs and implicated to the current controversial observations on the expression of adaptive response.

Adaptation, Physiological↗
PubMed2004

Infant immune response to human rotavirus serotype G1 vaccine candidate reassortant WI79-9: different dose response patterns to virus surface proteins VP7 and VP4.

BACKGROUND: Rotavirus is the leading cause of morbidity from gastroenteritis in the developed world and the leading cause of mortality from viral gastroenteritis (estimated 600000 deaths) worldwide. G1 is the most prevalent human serotype. Reassortant rotavirus between simian rotavirus RRV or bovine rotavirus WC3 and human strain rotaviruses have been extensively tested as candidate vaccines. Rotavirus (RV) reassortant strain WI79-9 consists of a human (strain WI79) G1 serotype VP7 surface protein on a bovine (strain WC3) background. It is a key component of a pentavalent (G1, G2, G3, G4 and P1) WC3 reassortant vaccine candidate, RotaTeq, now being tested in Phase III clinical trials. METHODS: We studied 84 infants between the ages of 2 and 8 months who received 3 oral doses of WI79-9. Serum neutralizing antibody was measured to the human (WI79 serotype P1 G1) and bovine (WC3 serotype P7 G6) parent RV after each dose. A significant response was defined as a > or =3-fold rise in antibody titer between the predose and postdose sera. RESULTS: In two separate cohorts of vaccinees given three doses of WI79-9 reassortant rotavirus, 68 to 75% of infants demonstrated a significant response to WC3 (VP4, P7) after Dose 1, fewer (24 to 39%) responses were detected after Dose 2 and rare (0 to 4%) additional responses occurred after Dose 3. The cumulative response rate to WC3 after three doses was 95% in both trials. In contrast 23 to 37% had a significant response to WI79 (VP7, G1) after Dose 1, and 57 to 61% had a significant response after Dose 2. Additional significant responses after Dose 3 led to a cumulative response of 70 to 84%. CONCLUSION: Two doses of G1 reassortant WI79 were necessary to induce significant antibody responses to human G1 (VP7) antigen in >50% of infants. Three doses were required to achieve significant antibody responses to VP7 in >70% of infants.

Animals↗
PubMed1989

Activation of the serum response element and 12-O-tetradecanoylphorbol-13-acetate response element by the activated c-raf-1 protein in a manner independent of protein kinase C.

Transfection of the cDNA encoding the activated c-raf-1 protein or addition of 12-O-tetradecanoylphorbol-13-acetate (TPA) or dibutyryl cAMP to NIH/3T3 cells activated the c-fos gene enhancer linked to the chloramphenicol acetyltransferase or luciferase reporter gene. Prolonged treatment of NIH/3T3 cells with phorbol 12,13-dibutyrate caused down-regulation of protein kinase C. In these cells, addition of TPA did not stimulate the c-fos gene enhancer any more, but transfection of the c-raf-1 cDNA or addition of dibutyryl cAMP still stimulated the c-fos gene enhancer to the same extent as those induced in the control cells. Transfection of the c-raf-1 cDNA or addition of TPA to NIH/3T3 cells stimulated the serum response element and TPA response element but not the cAMP response element. In contrast, addition of dibutyryl cAMP to NIH/3T3 cells stimulated the cAMP response element but not the serum response element or TPA response element. These results indicate that the activated c-raf-1 protein stimulates the serum response element and TPA response element in a manner independent of protein kinase C and cAMP-dependent protein kinase. Since the c-fos gene enhancer has been shown to contain the serum response element and cAMP response element, it is most likely that the c-raf-1 protein is involved in the regulation of c-fos gene expression through the serum response element.

Animals↗