Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “rapid response”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1999

Time-resolved monitoring of electrogenic Na+-Ca2+ exchange in the isolated cardiac sarcolemma vesicles by using a rapid-response fluorescent probe.

As a major Ca exit system in myocytes, the electrogenic Na+-Ca2+ exchange is exposed to rapid changes of regulatory factors (e.g., cytosolic Ca) during the excitation-contraction coupling. The dynamic aspects of the exchanger response to regulatory factors have not been resolved in the past due to technical limitations. Here, we describe stopped-flow protocols for monitoring the electrogenic activity of Na+-Ca2+ exchange in cardiac sarcolemma vesicles by using a rapid-response voltage-sensitive dye Merocyanine-540 (M540). The M540 signal of Nao-dependent Ca efflux is generated by mixing the Ca-loaded vesicles with Na buffer, yielding 160 mM extravesicular Na and 6 microM Cafree. This signal is inhibited by a cyclic peptide blocker (FRCRCFa), by a Ca ionophore (ionomycin), or by an electrogenic uncoupler (valinomycin or FCCP). The M540 signal of Nao-dependent Ca efflux shows a rapid pre-steady-state burst (210 s-1), followed by slow steady-state phase (</=5 s-1). Extravesicular (cytosolic) Ni inhibits both phases with an IC50 of 0.80 +/- 0.24 mM. At an extravesicular pH of 6.0, the Nao-dependent Ca efflux is able to generate the M540 signal, thereby supporting the idea that the stoichiometry of Na+-Ca2+ exchange is not altered at low pH [Khanashvili, D., et al. (1995) Biochemistry 34, 10290-10297]. The M540 signal of Nao-dependent Ca efflux is lost when the extravesicular Cafree concentration drops to 0.2 microM. This effect cannot be explained by a lack of Ca access to extravesicular (cytosolic) transport sites, because the reaction of Nao-dependent Ca efflux utilizes intravesicular Ca as a substrate. These data suggest that in sarcolemma vesicles a regulatory cytosolic Ca site controls the exchanger activity. The properties of this putative regulatory site do not resemble the properties of the "slow" Ca regulatory mode, observed in electrophysiological studies. Under saturating ionic conditions, the Nao-dependent Ca efflux generates the initial rates of 21 mV/ms in the vesicles with a diameter of 3000-5000 A. If a site density of 300-400 exchangers/micrometer2 and a vesicular surface of 0.5 micrometer2 are assumed, each vesicle may contain 150-200 exchanger molecules with a maximal turnover rate of 4000-5000 s-1. This upper limit for turnover (no matter what the site density is) may put considerable restrictions on the exchanger capacity to mediate Ca entry in the cell under physiologically related conditions.

Aniline Compounds↗
PubMed2005

The bisphosphonate acute phase response: rapid and copious production of proinflammatory cytokines by peripheral blood gd T cells in response to aminobisphosphonates is inhibited by statins.

The bisphosphonates are a novel class of drug that have been registered for various clinical applications worldwide. Bisphosphonates, and in particular the aminobisphosphonates (nBPs), are known to have a number of side-effects including a rise in body temperature and accompanying flu-like symptoms that resemble a typical acute phase response. The mechanism for this response has been partially elucidated and appears to be associated with the release of tumour necrosis factor (TNF)alpha and interleukin (IL)6, although the effector cells that release these cytokines and the mechanism of action remain enigmatic. Here, we show that the nBP-induced acute phase response differs from the typical acute phase response in that CD14+ cells such as monocytes and macrophages are not the primary cytokine producing cells. We show that by inhibiting the mevalonate pathway, nBPs induce rapid and copious production of TNFalpha and IL6 by peripheral blood gammadelta T cells. Prior treatment with statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, blocks nBP-induced production of these proinflammatory cytokines by gammadelta T cells and may offer a means of avoiding the associated acute phase response. In addition, our findings provide a further mechanism for the anti-inflammatory effects attributed to inhibitors of HMG CoA reductase.

Acute-Phase Reaction↗
PubMed1986

Squamous cell carcinoma of the thymus: a case report of rapid response to cyclophosphamide, doxorubicin, cisplatin, and prednisone.

A woman with unresectable squamous cell carcinoma of the thymus was treated with combination chemotherapy consisting of cyclophosphamide, adriamycin, cisplatin, and prednisone. Rapid tumor response and hyperuricemia occurred within 10 days after the first course of chemotherapy. Mediastinal irradiation was given after two courses of chemotherapy. Chemotherapy was continued until the total dose of adriamycin reached 450 mg/m2. The patient is alive and well in remission more than 111 weeks after therapy was begun and more than 63 weeks after treatment was discontinued. Further study of this chemotherapeutic regimen in squamous cell carcinoma of the thymus is needed. Monitoring of serum uric acid levels may be required.

Amiloride↗
PubMed1976

A rapid response system for out-of-hospital cardiac emergencies.

We have reviewed several aspects of our initial 5 years' experience with an out-of-hospital emergency medical care system. This system is stratified and provides for rapid primary response and, when indicated, secondary response by specially trained paramedical personnel. Patient care is physician-supervised and closely monitored. Although considerable attention has been directed to acute complications of ischemic heart disease, particularly the problem of sudden cardiac death, the system is broadly based and responds to all medical emergencies. We are impressed with the ability of nonphysicians to acquire certain medical skills and judgment. Indeed, the effectiveness of this system is largely dependent on paramedical personnel. Such systems of prehospital emergency medical care will probably have an impact greater than that of hospital coronary care units in reducing the mortality from ischemic heart disease.

Coronary Care Units↗
PubMed2004

Integrating rapid responses to 1,25-dihydroxyvitamin D3 with transcriptional changes in osteoblasts: Ca2+ regulated pathways to the nucleus.

It is well established that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment of target cells including osteoblasts activates both membrane-initiated rapid Ca2+ responses linked to influx through voltage sensitive Ca2+ channels (VSCCs) and longer term nuclear receptor-mediated changes in gene expression. We recently reported use of a cDNA microarray strategy to identify transcriptional changes after 3 and 24h of treatment with 1,25(OH)2D3 and with an analog of 1,25(OH)2D3 (25(OH)-16ene-23yne-D3 [AT]) that activates Ca2+ influx without binding to the nuclear receptor. Among 5000 different clones on the array filters, we identified families of genes in osteoblasts that were altered two-fold or greater following treatment with 1,25(OH)2D3 or analog AT for 3h. Cluster analysis further revealed complex patterns of changes in gene expression, indicative of multiple pathways to the nucleus. Evidenced by changes in target gene expression, activation of a Ca2+/CaMK/CREB/CRE pathway clearly occurs and modulates expression of a variety of genes associated with changes in protein secretion including those involved in paracrine regulation of bone resorption, RANKL and osteoprotegerin (OPG). The changes in gene expression can be inhibited by L-type VSCC channel blockers, confirming the role of Ca2+ entry in pathway activation. These findings provide clear evidence of rapid changes in gene expression associated with Ca2+ influx after treatment with 1,25(OH)2D3, and open the door to novel nuclear receptor-independent signaling pathways that affect gene transcription.

Animals↗
PubMed2001

Rapid response of severe refractory metastatic Crohn's disease to infliximab.

A case is described of a middle-aged female who developed an aggressive form of biopsy-proven metastatic Crohn's disease involving the inguinal, perineal and submammary areas. Her condition had been unresponsive to topical and systemic corticosteroids, antibiotics, immunosuppressives, and repeated surgical debridement. Administration of infliximab resulted in a rapid clinical response with subjective improvements in pain and general well-being, and an objective decline in exudate, erythema and size of the lesions. Infliximab may be a suitable therapeutic option in patients with metastatic Crohn's disease.

Antibodies, Monoclonal↗
PubMed1995

Rapid Response of the Yield Threshold and Turgor Regulation during Adjustment of Root Growth to Water Stress in Zea mays.

Responses of cortical cell turgor (P) following rapid changes in osmotic pressure ([pi]m) were measured throughout the elongation zone of maize (Zea mays L.) roots using a cell pressure probe and compared with simultaneously measured root elongation to evaluate: yield threshold (Y) (minimum P for growth), wall extensibility, growth-zone radial hydraulic conductivity (K), and turgor recovery rate. Small increases in [pi]m (0.1 MPa) temporarily decreased P and growth, which recovered fully in 5 to 10 min. Under stronger [pi]m (up to 0.6 MPa), elongation stopped for up to 30 min and then resumed at lower rates. Recoveries in P through solute accumulation and lowering of Y enabled growth under water stress. P recovery was as much as 0.3 MPa at [pi]m = 0.6 MPa, but recovery rate declined as water stress increased, suggesting turgor-sensitive solute transport into the growth zone. Under strong [pi]m, P did not recover in the basal part of the growth zone, in conjunction with a 30% shortening of the growth zone. Time courses showed Y beginning to decrease within several minutes after stress imposition, from about 0.65 MPa to a minimum of about 0.3 MPa in about 15 min. The data concerning Y were not confounded significantly by elastic shrinkage. K was high (1.3 x 10-10 m2 s-1 MPa-1), suggesting very small growth-induced water potential gradients.

Journal Article↗
PubMed1993

Does the rapid response to cisplatin-based chemotherapy justify its use as primary treatment for intracranial germ-cell tumours?

We reviewed presentation, diagnostic problems and outcome of eight cases of primary intracranial germ-cell tumour (4 germinoma, 4 teratoma) treated with Cisplatin-based chemotherapy at our centre over the last ten years. Three patients received primary chemotherapy with Cisplatin-based regimens followed by radiotherapy for subsequent relapse, two were treated with a combination of chemotherapy and external radiotherapy, and three received chemotherapy for relapse after radiotherapy. The response to Cisplatin-based chemotherapy was rapid, with some patents exhibiting symptomatic improvement within 24 h. Four patients achieved complete remission within 21 days, and three of these have remained progression-free. Four patients in total have survived for 32 to 128+ months. Six of seven patients tested pre-treatment had central diabetes insipidus and five had partial anterior pituitary failure. The endocrine deficit progressed in two, with no recovery in any patient. It is arguable that chemotherapy should be the primary therapy in all such cases diagnosed on the basis of tumour markers and imaging, with surgery and/or radiotherapy as later options. As these tumours are rare, such questions can only be answered by collaboration studies.

Adolescent↗
PubMed1985

A case of herpes zoster associated encephalitis with rapid response to acyclovir.

A case of herpes zoster encephalitis which responded very rapidly to acyclovir is presented. The differential serum: cerebrospinal fluid antibody response was followed and its value in making the diagnosis is discussed. The penetration of acyclovir into the cerebrospinal fluid was measured, and found to be in agreement with predicted values.

Acyclovir↗
PubMed2000

Abnormal myocardial mechanics in Kawasaki disease: rapid response to gamma-globulin.

BACKGROUND: The time course and rate of recovery of myocardial dysfunction in association with Kawasaki disease in response to intravenous gamma-globulin is unknown and may provide mechanistic clues. METHODS AND RESULTS: The acute changes in myocardial contractility in 25 patients with Kawasaki disease were evaluated by noninvasive stress-shortening and stress-velocity analysis. Echocardiograms were performed before and then daily for 4 days during which the patients received gamma-globulin 1.6 to 2 g/kg. Before treatment, contractility was abnormally low (<2 SD) in 14 patients (56%). Contractility increased significantly (2 SD increase) in 17 (68%), including 13 of 14 with depressed contractility and 4 whose initial contractility fell within normal limits. Of the 14 patients with depressed contractility, 8 (57%) normalized within 24 hours and a further 5 (35.7%) normalized within 6 months. A clinical response to treatment (fall in C-reactive protein by 50% and/or resolution of fever within 4 days) was seen in 22 patients (88%). Contractility increased in 17 of the 22 clinical responders and was normal before therapy in the other 5. The 3 patients who did not respond clinically also had no change in contractility with gamma-globulin therapy. Long-term (more than 12 months) follow-up was available in 19 patients. All patients had normal contractility at late follow-up. CONCLUSIONS: More than half the patients with Kawasaki disease have abnormal contractility at presentation. Myocardial response to gamma-globulin therapy is associated with rapid improvement in myocardial mechanics, with a high concordance between the clinical and myocardial response to therapy. The speed of recovery suggests that depressed contractility in patients with Kawasaki disease is caused by a rapidly reversible process such as circulating toxins or activated cytokines. Long-term outcome is good even in those patients with slow recovery of myocardial function.

Child, Preschool↗
PubMed1989

Rapid response to Con A by CD4+CD45R- rat memory lymphocytes as compared to CD4+CD45R+ lymphocytes.

Functionally distinct subpopulations within the CD4+ subset of T lymphocytes have been described in man, rat, and mouse. In the rat different functions have been assigned to CD45R+ and CD45R- T helper cells. The CD45R+ in contrast to the CD45R- T helper cells have been reported to produce IL-2 and to proliferate well in response both to Con A and in MLR. In the present investigation the kinetics of the response to Con A by the CD45R+ and CD45R- rat T helper subsets have been analyzed. We confirm a strong proliferative response to Con A by CD4+CD45R+ rat T lymphocytes and also that they are the best IL-2 producers. We further demonstrate that CD4+CD45R- cells also produce IL-2, although in order to appreciate this production quantitatively by assays of the culture supernatants it was necessary to block IL-2 absorption by IL-2 receptor (IL-2R) antibodies. This blockage was of importance also in comparisons of the two subsets, since they showed different kinetics of IL-2R appearance. It is demonstrated that the CD4+CD45R- cells respond more rapidly to Con A than the CD4+CD45R+ cells as reflected by phenotypic conversion, IL-2 production, and proliferation. The fast response of the CD4+CD45R- T subset shown in the present study of rat cells and analogous studies of human cells suggests that the memory compartment of T cells besides other characteristics also has the capacity for a more rapid response than naive lymphocytes.

Animals↗
PubMed2006

A 40-basepair VNTR polymorphism in the dopamine transporter (DAT1) gene and the rapid response to antidepressant treatment.

Finding predictors of the response to antidepressant therapy is a major goal of molecular psychiatry. The genes encoding the serotonin (SERT) and dopamine (DAT1) transporters are among the possible candidate genes modulating an individual's antidepressant response. In a naturalistic prospective cohort study with a total of 190 fully assessed patients, improvement of depression symptoms during the 3 weeks following initiation of antidepressant therapy was recorded using the 21-item Hamilton Depression Rating Scale (HDRS). The SLC6A3 3' UTR 40-bp variable number of tandem repeats (VNTR) and the SLC6A4 5' 44-bp insertion/deletion polymorphism were analyzed by polymerase chain reaction. There was a significantly smaller number of rapid responders among homozygous carriers of the DAT1 9-repeat allele (9/9) than among heterozygous (9/10) and homozygous (10/10) carriers of the 10-repeat allele (19 versus 37 versus 52%, respectively, P=0.0037). Median decline in HDRS score was 35, 40, and 52% in patients with the 9/9, 9/10, and 10/10 genotypes, respectively (P=0.013). The effect was found in all classes of medications (selective serotonin reuptake inhibitors (SSRIs), tricyclics, mirtazapine, venlafaxine) and statistically significant also within the subgroup of patients having received SSRIs. The serotonin promoter insertion/deletion genotype had no effect in the entire study group, but there was an insignificant trend of better response in the l/l and l/s carriers who received SSRIs or mirtazapine. In conclusion, the dopamine transporter VNTR polymorphism influenced rapid response to antidepressant therapy. Compared with homozygous carriers of the 10-repeat allele, carriers of the 9/10 genotype had an odds ratio (OR) calculated by logistic regression analysis of 1.6 (95% CI 0.8-3.2) and carriers of the 9/9 genotype had an OR of 6.0 (1.5-24.4) for no or poor response. Further studies are required to confirm this clinical association and to elucidate the underlying mechanisms.

Adult↗
PubMed2003

Rapid responses to high temperature and desiccation but not to low temperature in the freeze tolerant sub-Antarctic caterpillar Pringleophaga marioni (Lepidoptera, Tineidae).

A broad definition of rapid cold hardening (RCH) is that it is the process whereby insects increase their survival of a sub-zero temperature after a brief (h) pre-exposure to a less severe low temperature. The effects of various pre-treatments on survival of two h at -7.9 degrees C were investigated in the freeze tolerant sub-Antarctic caterpillar Pringleophaga marioni (Lepidoptera: Tineidae), the first time RCH has been investigated in a freeze tolerant arthropod. All caterpillars froze when exposed to -7.9 degrees C, and none of the low temperature pre-treatments (-5, 0, 5 and 15 degrees C, as well as -5 degrees C and 0 degrees C with a delay before freezing) nor slow cooling (0.1 degrees C/min) elicited any improvement in survival of -7.9 degrees C as compared to controls. However, high temperature treatments (25, 30 and 35 degrees C), desiccation and acclimation for 5 days at 0 degrees C did result in significant increases in survival of the test temperature, possibly as a result of heat shock protein production. Haemolymph osmolality was elevated only by the 35 degrees C pre-treatment. It is suggested that the unpredictable environment of Marion Island means that P. marioni must always be physiologically prepared to survive cold snaps, and that this year-round cold hardiness therefore supersedes a rapid cold hardening response.

Acclimatization↗
PubMedDate not supplied

Ligands for the vitamin D endocrine system: different shapes function as agonists and antagonists for genomic and rapid response receptors or as a ligand for the plasma vitamin D binding protein.

The integrated operation of the vitamin D endocrine system which produces the steroid hormone 1alpha,25(OH)(2)-vitamin D(3) (1alpha,25(OH)(2)D(3)) is dependent on four classes of proteins each of which have inherent in their secondary and tertiary structure a ligand binding domain (LBD) that allows the stereospecific binding of 1alpha,25(OH)(2)D(3) or related analogs as a substrate or ligand. These LBDs include: (a) the cytochrome P450 enzymes in the liver, kidney, and other tissues which metabolize vitamin D(3) into biologically active metabolites; (b) the plasma vitamin D binding protein (DBP) which selectively transports these hydrophobic molecules to the various target organs of the vitamin D endocrine system; (c) the nuclear receptor VDR(nuc) that is involved in regulation of gene transcription in over 30 cell types which possess this receptor; and (d) a plasma membrane receptor, VDR(mem), that is involved in initiation of signal transduction pathways which generate rapid biological responses. This article reviews the evidence that supports the conclusions that the LBD of the DBP, VDR(mem) and VDR(nuc) each select as their preferred ligand a unique shape of the conformationally flexible 1alpha,25(OH)(2)D(3). Two critical aspects of the conformationally flexible 1alpha,25(OH)(2)D(3) molecule which defines the optimum ligand shape are (a) the orientation and relative rigidity of the flexible 8 carbon side chain and (b) the position of the A ring in relation to the C/D rings as determined by the extent of rotation around the 6,7 single carbon bond of the seco B ring. These conclusions are based on consideration of structure-function studies of over 300 analogs of 1alpha,25(OH)(2)D(3), of these, 22 analogs are highlighted in this presentation.

Animals↗
PubMed1987

Induction of a rapidly responsive hepatic gene product by thyroid hormone requires ongoing protein synthesis.

The regulation of a gene, designated spot 14, which is rapidly induced in rat liver in response to 3,5,3'-triiodo-L-thyronine (T3) was studied as a model for exploring the molecular basis of thyroid hormone action. The time course of induction of the nuclear precursor to spot 14 mRNA after intramuscular injection of T3 displayed a very short lag period of between 10 and 20 min. The rapidity of this effect suggests that the induction in gene expression occurs as a primary response to the hormone-receptor interaction. The protein synthesis inhibitor cycloheximide injected 15 min before T3 completely blocked the accumulation of nuclear precursor RNA 30 min after T3 treatment. Emetine, an inhibitor of protein synthesis which acts by a different mechanism than cycloheximide, also blocked the induction of the spot 14 nuclear precursor RNA. The increased rate of spot 14 gene transcription observed after T3 treatment, as measured by nuclear run-on assay, was similarly completely abolished in the presence of cycloheximide. In addition, ongoing protein synthesis was required for maintaining spot 14 nuclear precursor RNA at induced levels in animals previously treated with T3. On the other hand, cycloheximide had no effect on T3 uptake or binding to the nuclear receptor during the 45-min time frame studied. The paradox of the rapid kinetics of induction and the requirement of ongoing protein synthesis may be explained by a protein with an extremely short half-life which is necessary for T3 induction of the spot 14 gene.

Animals↗
PubMed2002

Non-genomic convergent and divergent signalling of rapid responses to aldosterone and estradiol in mammalian colon.

Studies from our laboratory have demonstrated rapid ( < 1 min) non-genomic activation of Na(+)-H(+) exchange, K(+) recycling, PKC activity and a PKC-dependent Ca(2+) entry through L-type Ca(2+) channels specifically by mineralocorticoids in distal colon. Aldosterone directly stimulates the activity of the PKC alpha isoform (but not PKC delta, PKC epsilon and PKC zeta) in a cell-free assay system containing only purified commercially available enzyme, appropriate substrate peptide, co-factors and lipid vesicles. The primary ion transport target of the non-genomic signal transduction cascade elicited by aldosterone in epithelia is the Na(+)-H(+) exchanger. In isolated colonic crypts, aldosterone produced a PKC alpha sensitive intracellular alkalinisation within 1 min of hormone addition. Intracellular alkalinisation upregulates an ATP-dependent K(+) channel, which is involved in K(+) recycling to maintain the electrical driving force for Na(+) absorption, while inhibiting a Ca(2+) -dependent K(+) channel, which generates the charge balance for Cl(-) secretion. The non-genomic response to aldosterone in distal colon appears to enhance the capacity for absorption while down-regulating the potential for secretion. We have also demonstrated rapid (< 1 min) non-genomic activation of Na(+)-H(+) exchange, K(+) recycling, PKC alpha activity, and a PKC delta- and PKA-dependent Ca(2+) entry through di-hydropyridine-blockable Ca(2+) channels specifically by 17beta-estradiol in distal colon. These rapid effects are female gender specific and are insensitive to inhibitors of the classical estrogen receptor (ER). 17 beta-Estradiol directly stimulated the activity of both PKC delta and PKC alpha (but not PKC epsilon or PKC zeta) in a cell-free assay system. E2 rapidly inhibited basolateral K(Ca) channel activity which would be expected to result in an acute inhibition of Cl(-) secretion. Physiological concentrations of E2 (0.1-10 nM) reduced both basal and secretagogue-induced Cl(-) secretion. This anti-secretory effect of E2 is sensitive to PKC inhibition, intracellular Ca(2+) chelation, and is female gender specific and insensitive to inhibitors of the classical ER. These observations link rapid non-genomic activation of second messengers with a rapid gender-specific physiological effect in the whole tissue. Aldosterone and E2 differ in their protein kinase signal transduction and both hormones stimulate specific PKC isoforms indicating both common and divergent signalling systems for salt-retaining steroid hormones. The physiological function of non-genomic effects of aldosterone and estradiol is to shift the balance from net secretion to net absorption in a pluripotential epithelium.

Aldosterone↗
PubMed2005

Rapid response to alefacept given to patients with steroid resistant or steroid dependent acute graft-versus-host disease: a preliminary report.

We evaluated the effect of alefacept (Amevive), a novel dimeric fusion protein, in steroid resistant/dependent acute graft-versus-host-disease (aGVHD). Seven patients were treated in eight aGVHD episodes. GVHD grade at treatment initiation and at peak ranged 2-4 (median 2.5) and 2-4 (median 4), respectively. System involvement at GVHD peak included skin (n=7), gastrointestinal tract (n=5) and liver (n=3). All patients responded. However, one patient with skin GVHD and two with gastrointestinal GVHD featuring an early initial response (IR) exacerbated and CR was not achieved. Skin GVHD responded rapidly with a median of 1 day to IR and 7 days to CR. Intestinal response was slower with median 7.5 days to IR. Of the four patients that achieved IR, CR was achieved in only one (40 days to CR). None of the patients had significant hepatic GVHD before treatment so no hepatic effect of alefacept could be determined. No immediate alefacept-related side effects were observed. Late side effects included infections (aspergillus sinusitis, pneumonia, bacteremia, pharyngeal thrush), pancytopenia and hemorrhagic cystitis. Three patients had CMV reactivation while on alefacept. We conclude that alefacept may have a beneficial effect in controlling aGVHD. Further investigations in larger cohorts of patients and controlled studies are warranted.

Acute Disease↗