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Biomedical subjects

B A Williams

Publications and source records attributed to B A Williams.

At least 37 records · Page 2Linked to original sources
PubMed2001

Intercessory prayer and cardiovascular disease progression in a coronary care unit population: a randomized controlled trial.

OBJECTIVE: To determine the effect of intercessory prayer, a widely practiced complementary therapy, on cardiovascular disease progression after hospital discharge. PATIENTS AND METHODS: In this randomized controlled trial conducted between 1997 and 1999, a total of 799 coronary care unit patients were randomized at hospital discharge to the intercessory prayer group or to the control group. Intercessory prayer, ie, prayer by 1 or more persons on behalf of another, was administered at least once a week for 26 weeks by 5 intercessors per patient. The primary end point after 26 weeks was any of the following: death, cardiac arrest, rehospitalization for cardiovascular disease, coronary revascularization, or an emergency department visit for cardiovascular disease. Patients were divided into a high-risk group based on the presence of any of 5 risk factors (age = or >70 years, diabetes mellitus, prior myocardial infarction, cerebrovascular disease, or peripheral vascular disease) or a low-risk group (absence of risk factors) for subsequent primary events. RESULTS: At 26 weeks, a primary end point had occurred in 25.6% of the intercessory prayer group and 29.3% of the control group (odds ratio [OR], 0.83 [95% confidence interval (CI), 0.60-1.14]; P=.25). Among high-risk patients, 31.0% in the prayer group vs 33.3% in the control group (OR, 0.90 [95% CI, 0.60-1.34]; P=.60) experienced a primary end point. Among low-risk patients, a primary end point occurred in 17.0% in the prayer group vs 24.1% in the control group (OR, 0.65 [95% CI, 0.20-1.36]; P=.12). CONCLUSIONS: As delivered in this study, intercessory prayer had no significant effect on medical outcomes after hospitalization in a coronary care unit.

Age Factors↗
PubMed2000

An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemoreceptor cells.

The biophysical and pharmacological properties of an oxygen-sensitive background K+ current in rat carotid body type-I cells were investigated and compared with those of recently cloned two pore domain K+ channels. Under symmetrical K+ conditions the oxygen-sensitive whole cell K+ current had a linear dependence on voltage indicating a lack of intrinsic voltage sensitivity. Single channel recordings identified a K+ channel, open at resting membrane potentials, that was inhibited by hypoxia. This channel had a single channel conductance of 14 pS, flickery kinetics and showed little voltage sensitivity except at extreme positive potentials. Oxygen-sensitive current was inhibited by 10 mM barium (57% inhibition), 200 microM zinc (53% inhibition), 200 microM bupivacaine (55% inhibition) and 1 mM quinidine (105 % inhibition). The general anaesthetic halothane (1.5%) increased the oxygen-sensitive K+ current (by 176%). Halothane (3 mM) also stimulated single channel activity in inside-out patches (by 240%). Chloroform had no effect on background K+ channel activity. Acidosis (pH 6.4) inhibited the oxygen-sensitive background K+ current (by 56%) and depolarised type-I cells. The pharmacological and biophysical properties of the background K+ channel are, therefore, analogous to those of the cloned channel TASK-1. Using in situ hybridisation TASK-1 mRNA was found to be expressed in type-I cells. We conclude that the oxygen- and acid-sensitive background K+ channel of carotid body type-I cells is likely to be an endogenous TASK-1-like channel.

Acidosis↗
PubMed2000

Estimating the extent of degradation of ruminant feeds from a description of their gas production profiles observed in vitro: comparison of models.

An evaluation of general models that describe gas production profiles is presented. The models are derived from first principles by considering a simple three-pool scheme and permit the extent of ruminal degradation to be calculated, as described in the companion paper. The models evaluated were the generalized Mitscherlich, simple Mitscherlich, generalized Michaelis-Menten, simple Michaelis-Menten, Gompertz, and logistic. Five sets of gas production data consisting of 216 curves, obtained using a wide range of feeds (including straw, hay, silage, grain and various byproducts), were analysed to study the performance of these gas production models. Application of the non-sigmoidal models (simple Mitscherlich and Michaelis-Menten) to the data resulted in convergence problems and these models were found to be inadequate in many cases. Based on results of a pairwise comparison between models (variance ratio test), ranking of residual mean squares, lack-of-fit test, and of analyses of residuals, the generalized Mitscherlich and the generalized Michaelis-Menten models seemed particularly suited because of their flexibility to encompass sigmoidal and non-sigmoidal shapes of gas production profiles, whether symmetrical or not.

Animal Feed↗
PubMed2000

Process analysis in outpatient knee surgery: effects of regional and general anesthesia on anesthesia-controlled time.

BACKGROUND: The performance of anesthetic procedures before operating room entry (e.g., with either general or regional anesthesia [RA] induction rooms) should decrease anesthesia-controlled time in the operating room. The authors retrospectively studied the associations between anesthesia techniques and anesthesia-controlled time, evaluating one surgeon performing a single procedure over a 3-yr period. The authors hypothesized that, using the anesthesia care team model, RA would be associated with reduced anesthesia-controlled time compared with general anesthesia (GA) alone or combined general-regional anesthesia (GA-RA). METHODS: The authors queried an institutional database for 369 consecutive patients undergoing the same procedure (anterior cruciate ligament reconstruction) performed by one surgeon over a 3-yr period (July 1995 through June 1998). Throughout the period of study, anesthesia staffing consisted of an attending anesthesiologist medically directing two nurse anesthetists in two operating rooms. Anesthesia-controlled time values were compared based on anesthesia techniques (GA, RA, or GA-RA) using one-way analysis of variance, general linear modeling using time-series and seasonal adjustments, and chi-square tests when appropriate. P < 0. 05 was considered significant. RESULTS: RA was associated with the lowest anesthesia-controlled time (11.4 +/- 1.3 min, mean +/- 2 SEM). GA-RA (15.7 +/- 1.0 min) was associated with lower anesthesia-controlled time than GA used alone (20.3 +/- 1.2 min). CONCLUSIONS: When compared with GA without an induction room for outpatients undergoing anterior cruciate ligament reconstruction, RA with an induction room was associated with the lowest anesthesia- controlled time. Managers must weigh the costs and time required for anesthesiologists and additional personnel to place nerve blocks or induce GA preoperatively in such a staffing model.

Adult↗
PubMed2000

Fate restriction in limb muscle precursor cells precedes high-level expression of MyoD family member genes.

The mechanisms by which pluripotent embryonic cells generate unipotent tissue progenitor cells during development are unknown. Molecular/genetic experiments in cultured cells have led to the hypothesis that the product of a single member of the MyoD gene family (MDF) is necessary and sufficient to establish the positive aspects of the determined state of myogenic precursor cells: i.e., the ability to initiate and maintain the differentiated state (Weintraub, H., Davis, R., Tapscott, S., Thayer, M., Krause, M., Benezra, R., Blackwell, T. K., Turner, D., Rupp, R., Hollenberg, S. et al. (1991) Science 251, 761-766). Embryonic cell type determination also involves negative regulation, such as the restriction of developmental potential for alternative cell types, that is not directly addressed by the MDF model. In the experiments reported here, phenotypic restriction in myogenic precursor cells is assayed by an in vivo 'notochord challenge' to evaluate their potential to 'choose' between two alternative cell fate endpoints: cartilage and muscle (Williams, B. A. and Ordahl, C. P. (1997) Development 124, 4983-4997). Two separate myogenic precursor cell populations were found to be phenotypically restricted while expressing the Pax3 gene and prior to MDF gene activation. Therefore, while MDF family members act positively during myogenic differentiation, phenotypic restriction, the negative aspect of cell specification, requires cellular and molecular events and interactions that precede MDF expression in myogenic precursor cells. The qualities of muscle formed by the determined myogenic precursor cells in these experiments further indicate that their developmental potential is intermediate between that of myoblastic stem cells taken from fetal or adult tissue (which lack mitotic and morphogenetic potential when tested in vivo) and embryonic stem cells (which are multipotent). We hypothesize that such embryonic myogenic progenitor cells represent a distinct class of determined embryonic cell, one that is responsible for both tissue growth and tissue morphogenesis.

Animals↗
PubMed1999

S.T.E.P.S.: a comprehensive program for controlling and monitoring access to thalidomide.

In July 1998, the US Food and Drug Administration approved the marketing of thalidomide for the treatment of cutaneous manifestations of erythema nodosum leprosum. To ensure that fetal exposure to this teratogenic agent does not occur, the manufacturer has instituted a comprehensive program to control prescribing, dispensing, and use of the drug. This program, known as the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S. [Celgene Corporation, Warren, New Jersey]), is based in part on experience gained with other drugs--specifically isotretinoin and clozapine--that offer important clinical benefits but carry the potential for serious harm. To achieve its goal of the lowest possible incidence of drug-associated teratogenicity, the S.T.E.P.S. program uses a three-pronged approach: (1) controlling access to the drug; (2) educating prescribers, pharmacists, and patients; and (3) monitoring compliance. Clinicians who wish to prescribe thalidomide must be registered in the S.T.E.P.S. Prescriber Registry and agree to prescribe the drug in accordance with S.T.E.P.S. patient eligibility criteria and monitoring procedures. Pharmacies must also register and agree to comply with patient identification and monitoring criteria. Finally, patients receive visual aids, including a videotape, written material, and verbal counseling about the benefits and risks of thalidomide therapy, the importance of not becoming pregnant during therapy, and the types of contraception required (including emergency contraception) and their availability. Women of childbearing potential must agree to undergo pregnancy testing before starting therapy and on a regular schedule during therapy. All patients must agree to complete a confidential survey about their compliance with contraception, testing, and drug therapy. The manufacturer is monitoring survey results and outcome data and is prepared to make whatever modifications to the S.T.E.P.S. program are necessary to ensure its effectiveness. In addition to minimizing the potential risk for fetal harm associated with thalidomide therapy, the S.T.E.P.S. program may provide a model for future cases in which a drug offers compelling benefits but poses profound risks unless its distribution is carefully controlled.

Dermatologic Agents↗
PubMed1999

Kinetics of rate-dependent shortening of action potential duration in guinea-pig ventricle; effects of IK1 and IKr blockade.

1. The kinetics of shortening of action potential duration (APD) following an increase in pacing rate, from 2 to 3.3 Hz, was characterized in guinea-pig ventricular preparations. Terikalant (RP62719), an inhibitor of the inwardly rectifying K+ current (IK1), and dofetilide, a specific inhibitor of the rapidly activating delayed-rectifier current (IKr), were applied to determine the effect of inhibition of these ion currents on slow APD shortening. 2. Action potentials were recorded from isolated guinea-pig ventricular myocytes using the perforated-patch patch-clamp technique, and monophasic action potentials were recorded from Langendorff-perfused guinea-pig ventricles using a contact epicardial probe. 3. Under control conditions, after an increase in pacing rate, APD immediately decreased, and then shortened slowly with an exponential time course. In ventricular myocytes, the time constant of this exponential shortening was 28+/-4 s and the amount of slow shortening was 21.9+/-0.9 ms (n=8) for an increase in rate from 2 to 3.3 Hz. Similar values were observed in Langendorff-perfused ventricles. 4. Terikalant dose-dependently increased APD and the increase was enhanced by rapid pacing ('positive' rate-dependence). The drug dose-dependently decreased the time constant of shortening and amount of slow APD shortening. In contrast, dofetilide, an inhibitor of IKr, which shows 'reverse' rate-dependent APD widening, had no significant effect on the time constant or amount of slow shortening. 5. These observations suggest that IK1 plays a role in rate-dependent shortening of APD. The results appear to support the hypothesis that 'reverse' rate-dependent effects of IKr blockers are due to these drugs not affecting the ion current(s) mediating intrinsic rate-dependent slow shortening of APD.

Action Potentials↗
PubMed1999

Value transmission in discrimination learning involving stimulus chains.

Rats learned a series of reversals of a positional discrimination in which responses to one lever led to delayed food and responses to a second lever led to no food. Interpolated within the delays leading to the different outcomes were two-link stimulus chains. The pairing of each stimulus element with the delayed outcome of food or no food varied across reversals. Either stimulus element could have the same correlation with outcome as occurred on the preceding reversal or the opposite correlation as on the preceding reversal. New reversals were acquired more quickly when both stimulus elements had the same status as during the preceding reversal, and were acquired most slowly when both stimulus elements had the opposite status as that of the preceding reversal. The rate of learning was intermediate when only one of the stimulus elements had the same status as that during the preceding reversal. All of the data are compatible with an interpretation in terms of backward chaining of stimulus value.

Animals↗
PubMed1999

Associative competition in operant conditioning: blocking the response-reinforcer association.

Naive rats were trained to leverpress with a 30-sec delay-of-reinforcement contingency from the start of training. In Experiment 1, the delay interval for different groups of subjects included a signal in the first 5 sec, a signal in the last 5 sec, or no signal at any time. Rats with the signal at the start of the delay interval learned most rapidly. Rats with the signal at the end of the delay failed to learn. In Experiment 2, a choice procedure was used, in which each of two levers was associated with its own 30-sec delay of reinforcement. The delay for one lever included a 5-sec signal at the end of the delay. The delay for the second lever had no signal in its 30-sec delay. Preference was in favor of the lever without the signal in the delay interval. The results demonstrate that the acquisition of new response can be blocked in a manner analogous to the blocking of Pavlovian conditioning.

Animals↗
PubMed1998

Knowing chops from chuck: roasting myoD redundancy.

The myf5 and myoD genes are implicated in the specification of vertebrate skeletal muscle. These genes have been thought to be functionally redundant because neonatal mice bearing homozygous null mutations in either gene show grossly normal muscle development. By analyzing the early embryonic development of the mutants, Michael Rudnicki and coworkers show that trunk muscle development is retarded in embryos bearing myf5 null mutations, while early limb and branchial arch muscle development is retarded by myoD null mutations. These results indicate that the myoD and myf5 genes are not redundant but that each controls the early specification of distinct muscle cell lineages.

Animals↗
PubMed1998

Benchmarking the perioperative process: II. Introducing anesthesia clinical pathways to improve processes and outcomes and to reduce nursing labor intensity in ambulatory orthopedic surgery.

STUDY OBJECTIVES: (1) To introduce anesthesia clinical pathways as a management tool to improve the quality of care; (2) to use the Procedural Times Glossary published by the Association of Anesthesia Clinical Directors (AACD) as a template for data collection and analysis; and (3) to determine the effects of anesthesia clinical pathways on surgical processes, outcomes, and costs in common ambulatory orthopedic surgery. DESIGN: Hospital database and patient chart review of consecutive patients undergoing anterior cruciate ligament reconstruction (ACLR) during academic years (AY) 1995-1996 and 1996-1997. Patient data from AY 1995-1996, during which no intraoperative anesthesia clinical pathways existed, served as historical controls. Data from AY 1996-1997, during which intraoperative anesthesia clinical pathways were used, served as the treatment group. Regional anesthesia options were routinely offered to patients in the clinical pathway. SETTING: Ambulatory surgery center in a teaching hospital. MEASUREMENTS AND MAIN RESULTS: The records of 503 ASA physical status I and II patients were reviewed. 1996-1997 patients underwent clinical pathway anesthesia care in which the intraoperative and postoperative anesthesia process was standardized with respect to symptom management, drugs, and equipment used. 1995-1996 patients did not have a standardized intraoperative and postoperative anesthetic course with respect to the management of common symptoms or to specific drugs and supplies used. Intervals described in the AACD Procedural Times Glossary, anesthesia drug and supply costs, and patient outcome variables (postoperative nursing interventions required and unexpected admissions), as influenced by the use of the anesthesia clinical pathway, were measured. Clinical pathway anesthesia care of ACLR in 1996-1997, which actively incorporated regional anesthesia options, reduced pharmacy and materials cost variability; slightly increased turnover time; improved intraoperative anesthesia and surgical efficiency, recovery times, and unexpected admission rates; and decreased the number of required nursing interventions for common postoperative symptoms. CONCLUSIONS: Clinical pathway patient management systems in anesthesia care are likely to produce useful outcome data of current practice patterns when compared with historical controls. This management tool may be useful in simultaneously containing costs and improving process efficiency and patient outcomes.

Adult↗
PubMed1998

Benchmarking the perioperative process: III. Effects of regional anesthesia clinical pathway techniques on process efficiency and recovery profiles in ambulatory orthopedic surgery.

STUDY OBJECTIVES: (1) To incorporate regional anesthesia options for common outpatient orthopedic surgery into clinical pathways; (2) to use the clinical pathway format and the Procedural Times Glossary published by the Association of Anesthesia Clinical Directors (AACD) as management tools to measure postoperative same-day surgery processes and discharge outcomes; and (3) to determine the effects of general, regional, and combined general-regional anesthesia on these processes and outcomes. DESIGN: Hospital database and patient chart review of consecutive patients undergoing anterior cruciate ligament reconstruction (ACLR) during academic years (AY) 1995-1996 and 1996-1997. Patient data from AY 1995-1996, during which no intraoperative anesthesia clinical pathway existed, served as historical controls. Data from AY 1996-1997, during which intraoperative anesthesia clinical pathways were used, served as the treatment group. SETTING: Ambulatory surgery center in a teaching hospital. MEASUREMENTS AND MAIN RESULTS: The records of 503 ASA physical status I and II patients were reviewed. 1996-1997 patients selected general anesthesia (+/- femoral nerve block) or epidural anesthesia, after which the remainder of the perioperative anesthesia process was standardized with respect to the drugs and equipment used. 1995-1996 patients did not necessarily have a choice in anesthesia technique and did not have a standardized perioperative anesthetic course with respect to specific drugs and supplies. Intervals described in the AACD Procedural Times Glossary, anesthesia drug and supply costs, and patient outcome variables (postoperative nursing interventions required and unexpected admissions), as influenced by anesthesia technique used, were measured. Combined general-regional anesthesia care for ACLR in 1996-1997, when compared with general anesthesia alone, led to increased pharmacy and materials costs and increased turnover time. However, patients with the combined technique showed improved recovery profiles and lower unexpected admission rates, and they required fewer nursing interventions for common postoperative symptoms. Patients receiving epidural anesthesia showed discharge outcomes similar to those patients receiving general anesthesia with femoral nerve block. Postanesthesia care unit bypass (fast-tracking) was more likely in clinical pathway regional anesthesia patients, when compared with the clinical pathway general anesthesia used. CONCLUSIONS: Clinical pathway regional anesthesia care for outpatient orthopedics may have a significant role in simultaneously containing costs and improving both process efficiency and patient outcomes.

Adult↗
PubMed1998

Z/I and A-band lattice spacings in frog skeletal muscle: effects of contraction and osmolarity.

A-band and Z-line/I-band lattice spacings were measured by small-angle X-ray diffraction from relaxed and isometrically-contracting whole frog sartorius muscles with lattice spacings reduced or swollen by changing the osmolarity of the bathing solution. A-band spacing increased by approximately 3% upon isometric contraction at reduced lattice spacings (245-356 mOsm) and decreased by approximately 1% at swollen spacings (172 mOsm), similarly to the behaviour of skinned muscles upon changing from the relaxed state to rigor. The Z/I lattice underwent a significant lattice expansion (3-8%) upon isometric contraction at all osmolarities, in qualitative agreement (but quantitative disagreement) with results from electron microscopy on mammalian skeletal muscle. Lattice areas calculated for the Z/I and A-band lattices indicate a barrel-shaped sarcomere in the resting state, which may provide a partial explanation for how longitudinal forces produced in the A-band can produce a radial expansive force in the Z-line during contraction. The radial component of cross-bridge stiffness was calculated from the A-band data for contracting muscle, using a lattice stability model incorporating structural, osmotic and electrostatic forces. The calculations gave a radial cross-bridge stiffness during contraction of about 9 x 10(5) N m-2, and outward radial force per thick filament in normal Ringer's solution of 6 x 10(-9) N, corresponding to a radial force per cross-bridge of 10(-11) N.

Animals↗
PubMed1998

The use of cumulative gas and volatile fatty acid production to predict in vitro fermentation kinetics of Italian ryegrass leaf cell walls and contents at various time intervals.

Differences between the fermentation characteristics of cell contents (CC) and protease-treated cell walls (CW) of young leaves of Italian ryegrass (Lolium multiflorum Lam.) cultivar Multimo (tetraploid), were studied in vitro. Gas and volatile fatty acid (VFA) production rates were measured at regular intervals, as was the degradability of organic matter (OM) of CW. The measured VFA were used to predict the gas production and fermentable OM using stoichiometric calculations. For CW the volume and kinetics of measured gas production were the same as those predicted from the VFA formed. In contrast, the measured gas production for CC was consistently less than predicted, indicating that the stoichiometric equations were not valid for rapidly fermenting substrates. For both CC and CW, the relative rate of acetic acid production levelled off more slowly than for other VFA, resulting in an increasing gas yield (in ml/g fermentable OM) after 12 (CW)-24 (CC) h incubation. Consequently, the fermentation of OM was not linearly related to gas production kinetics. For CW, the kinetics of decline of degradable OM and fermentable OM were the same, after correction for a constant 'lost fraction' of degradable OM of 205 g/kg OM. This work indicates the value of detailed studies of fermentation processes to evaluate herbage quality. In particular, the role of CC and the difference between degradation and fermentation require further attention.

Cell Wall↗
PubMed1997

Treatment of the P815 murine mastocytoma with cisplatin or etoposide up-regulates cell-surface Fas (CD95) expression and increases sensitivity to anti-Fas antibody-mediated cytotoxicity and to lysis by anti-CD3-activated killer-T cells.

We have investigated the effect of pre-treatment with the anti-cancer drugs cisplatin and etoposide on the susceptibility of P815 murine mastocytoma cells to lysis by murine spleen-derived anti-CD3-activated killer-T (AK-T) cells. A 20 hr pre-treatment with cisplatin (0.2-2 microg/ml) or etoposide (0.01-1 microg/ml) rendered P815 cells significantly more sensitive to AK-T cell-mediated lysis in a 4 hr 51Cr-release assay than untreated control tumor cells. At lower concentrations, pre-treatment with cisplatin or etoposide had no direct cytotoxic effects on P815 tumor cells, as measured by the MTT assay. AK-T cell-mediated killing of P815 tumor cells pre-treated with 2 microg/ml cisplatin or 1 microg/ml etoposide was only partially inhibitable by the Ca2+ chelator EGTA, suggesting that the Ca2+-independent Fas (CD95)/Fas ligand cytolytic pathway of AK-T cells contributes to cytotoxicity. In comparison to untreated control P815 cells, 2 microg/ml cisplatin- or 1 microg/ml etoposide-treated P815 cells exhibited increased expression of Fas mRNA and cell-surface Fas, which correlated with increased sensitivity to lysis by AK-T cells. In addition, pre-treatment with cisplatin or etoposide caused P815 tumor cells to become sensitive to the cytotoxic effects of anti-Fas antibody in a 4 hr 51Cr-release assay. Taken together, our results demonstrate that short-term exposure to concentrations of cisplatin and etoposide in the low cytotoxic range and below up-regulates Fas expression by P815 tumor cells, thereby facilitating cytotoxicity mediated through the Fas/Fas ligand cytolytic pathway.

Animals↗
PubMed1997

2-chloroadenosine stimulates granule exocytosis from mouse natural killer cells: evidence for signal transduction through a novel extracellular receptor.

The effect of 2-chloroadenosine (2CA), an adenosine receptor agonist, on the activation status of mouse natural killer (NK) cells was determined. Splenic lymphocytes incubated with 2CA exocytosed an NK cell-associated granzyme with N alpha-CBZ-L-lysine thiobenzyl ester (BLT) esterase activity in a dose- and time-dependent manner. Selective depletion of NK cells by anti-asialoGM1 antibody plus complement pretreatment confirmed that NK cells were the source of the BLT esterase activity. 2CA-induced granule exocytosis was not reduced in the presence of the nucleoside uptake blockers NBTI, dilazep, or dipyridamole, indicating the involvement of an extracellular receptor. However, adenosine or other A1, A2, or A3 cell-surface adenosine receptor agonists failed to trigger the exocytotic process. Furthermore, the nonselective adenosine receptor antagonist theophylline, as well as the selective A1 receptor antagonist DPCPX and the selective A2 receptor antagonist DMPX, did not interfere with 2CA-induced BLT esterase secretion. These data suggest that 2CA acts on NK cells via a novel (non-A1/A2/A3) cell-surface receptor. Genistein, a protein tyrosine kinase inhibitor, and calphostin C, a protein kinase C inhibitor, both interfered with 2CA-induced granule exocytosis. Pertussis toxin, an ADP-ribosylating toxin to which certain GTP-binding proteins are sensitive, also inhibited 2CA-stimulated BLT esterase release. In addition, 2CA-induced granule exocytosis was reduced in the presence of cyclosporin A, an inhibitor of Ca(2+)-dependent signaling pathways, and the Ca(2+)-chelating agent EGTA. We conclude that 2CA, acting through a novel extracellular receptor on mouse NK cells, triggers granule exocytosis via a Ca(2+)-dependent signal transduction pathway that is coupled to GTP-binding proteins and involves protein tyrosine kinase and protein kinase C activation.

2-Chloroadenosine↗