Search PubMed⌕ Search

Biomedical subjects

R Payne

Publications and source records attributed to R Payne.

At least 91 records · Page 5Linked to original sources
PubMed1994

The light response of Drosophila photoreceptors is accompanied by an increase in cellular calcium: effects of specific mutations.

Photoreceptors of dissociated Drosophila retinae were loaded with the fluorescent Ca2+ indicators, fluo-3 and Calcium Green-5N. In fluo-3-loaded, wild-type photoreceptors, a rapid increase in fluorescence (Ca2+ signal) accompanied the light-evoked inward current. Removal of extracellular Ca2+ greatly reduced the Ca2+ signal, indicating Ca2+ influx as its major cause. In Calcium Green-5N-loaded trp mutants, which lack a large fraction of the Ca2+ permeability underlying the light-evoked inward current, the Ca2+ signal was smaller relative to wild-type photoreceptors. Fluo-3-loaded norpA mutant photoreceptors, which lack a light-activated phospholipase C, generated no light-evoked inward current and no Ca2+ signal. The phosphoinositide pathway therefore appears necessary for both excitation and changes in cytosolic free Ca2+ concentration.

Aniline Compounds↗
PubMed1994

Neurochemical basis of interleukin 2-modified discrimination behaviour.

We trained one group of rats to discriminate 0.8 mg/kg intraperitoneal (i.p.) d-amphetamine from 1 ml/kg saline and the other to discriminate 0.3 mg/kg i.p. (+/-)-ethylketocyclazocine (EKC) from saline. Recombinant human interleukin 2 (rIL-2), 2 x 10(6) U/kg (or 8.2 nmol/kg) given i.p. 1 h prior to tests, potentiated responses elicited by 0.4 mg/kg d-amphetamine. This potentiation of d-amphetamine responses was suppressed by the opioid receptor antagonist naloxone (1 mg/kg) when administered i.p. together with IL-2. IL-2 (4 x 10(6) U/kg) alone produced EKC-like responses in the EKC-trained animals. The cytokine also potentiated 0.1 mg/kg EKC responses at 2 x 10(6) U/kg, an action that was suppressed by 1 mg/kg naloxone. Data from the present study show that IL-2 exerts the same neurochemical action as that previously observed with IFN-alpha for both d-amphetamine and EKC discrimination in rats.

Animals↗
PubMed1994

Facilitation of the responses to injections of inositol 1,4,5-trisphosphate analogs in Limulus ventral photoreceptors.

Injection of inositol 1,4,5-trisphosphate and its metabolically resistant analogs InsP3S3 and L-chiro-2,3,5-InsP3 into the ventral photoreceptors of Limulus results in the release of calcium from internal stores and in a current flow into the cells. We show here that the dependence of the current response on the amount of analog injected is supralinear. The injections also facilitate the responses to subsequent injections. We analyze the kinetics of the responses either by very slow application of the analogs directly into the lobe that is sensitive to InsP3 and light or by delivering a pulse into the nonsensitive lobe of the cell, in both cases creating a ramp of rising concentration in the sensitive region. Typically, a long latent period was followed by a strong brief inward current. The ratio between the latency and the duration of the response, defined as twice the time from half-amplitude to the peak of the response, reaches values greater than 10. Our analysis shows that this value cannot be attained within realistic models whose only nonlinearity is the cooperative binding of the ligand to its receptor. The observed ratio, however, can be achieved with a positive feedback model. Treatments that lead to partial depletion of calcium stores reversibly increase the latency of the response. We conclude that the mechanisms of the response of Limulus ventral eye to the metabolically resistant analogs of InsP3 probably involves a positive feedback mechanism and that the carrier of the feedback is likely to be Ca2+.

Animals↗
PubMed1994

The opioid mechanism of interferon-alpha action.

Rats were trained to discriminate the opioid receptor agonist ethylketocyclazocine (EKC) (0.3 mg/kg body weight, intraperitoneally) from saline. Interferon-alpha (IFN-alpha), when substituted for EKC, elicited a dose-related increase in EKC-like responses. This generalization of EKC responses was blocked by the opioid antagonist naloxone (1 mg/kg). Potentiation of responses to a low dose (0.1 mg/kg) of EKC by IFN-alpha (1 x 10(6) U/kg or 0.22 nmol/kg) was also observed. Data thus indicate the involvement of opioid neurons on the action of IFN-alpha. d-Amphetamine (0.8 mg/kg) was shown to potentiate both EKC (0.1 mg/kg) and IFN-alpha (1 x 10(6) U/kg). The present study confirms our previously proposed opioid-mediated dopaminergic mechanism of IFN-alpha.

Animals↗
PubMed1993

Fast desensitization of the response to InsP3 in Limulus ventral photoreceptors.

In Limulus ventral photoreceptor cells the time-course of the desensitization of InsP3 response was measured by an injection-pair paradigm. Pressure pulses of InsP3 were delivered into the cell with various interpulse intervals. The desensitization of the response to the second injection of each pair approached totality at 200 ms, which is the duration of the response to a single pressure pulse of InsP3. Lowering extracellular calcium did not affect the time-course of the desensitization. Lowering the temperature slowed down both the time-course of the response to InsP3 and the time-course of the desensitization to the same extent. These findings suggest that the desensitization is powerful enough and its onset fast enough to contribute to the transience of the InsP3 response. The time-course of the desensitization suggests it may influence light adaptation.

Adaptation, Physiological↗
PubMed1993

A lingering elevation of Cai accompanies inhibition of inositol 1,4,5 trisphosphate-induced Ca release in Limulus ventral photoreceptors.

Injection of inositol 1,4,5 trisphosphate (InsP3) into Limulus ventral photoreceptors causes an elevation of intracellular free Ca concentration (Cai) and depolarizes the photoreceptors. When measured with the photoprotein aequorin, the InsP3-induced Cai increase follows the time course of depolarization and declines within 1-2 s. However, sensitivity to further injections of InsP3 remains suppressed for several tens of seconds. The possibility that the suppression of Ca release (feedback inhibition) is due to a small lingering elevation of Cai, below the existing detection limit of aequorin, was investigated by measuring Cai with Ca-sensitive electrodes. Double-barreled, Ca-selective microelectrodes were used to pressure inject InsP3 and measure Cai at the same point. Light or InsP3 injections into the light-sensitive compartment depolarized the photoreceptors and induced an elevation of Cai that persisted for tens of seconds. Injections of InsP3 during the decay of Cai showed that sensitivity to InsP3 recovered as resting Cai approached the prestimulus level. The relationship between elevated Cai and feedback inhibition was very steep. An elevation of Cai of 1 microM or more was associated with inhibitions of 79 +/- 12.4% (SEM; n = 7) for the InsP3-induced Cai increase and of 76 +/- 8% for depolarizations. With a residual Cai elevation of 0.01 microM or less, the mean inhibition was 10 +/- 7.4% for InsP3-induced Cai increase and 6.6 +/- 4% for InsP3-induced depolarization. Injections of InsP3 into a light-insensitive compartment within the cell induced elevations of Cai with no associated depolarizations or feedback inhibition. To verify that a sustained elevation of Cai is necessary for inhibition of InsP3-induced Cai increase and depolarization, we injected ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA) between two injections of InsP3. Injection of 1 mM EGTA or the related Ca chelator BAPTA, delivered 750 ms after the first injection of InsP3, restored the peak depolarization caused by the second injection of InsP3 to > 80 +/- 3% of control, compared with 13 +/- 8% without an intervening injection of EGTA. Measurement of Cai with aequorin showed that an intervening injection of EGTA partially restored the InsP3-induced Cai increase. The results suggest that feedback inhibition of InsP3-induced Cai increase and depolarization is mediated by a lingering elevation of Cai and not by depletion of intracellular Ca stores.

Aequorin↗
PubMed1992

The latency of the response of Limulus photoreceptors to inositol trisphosphate lacks the calcium-sensitivity of that to light.

The latent period before depolarization of Limulus ventral photoreceptors by light flashes was compared with that following brief, intracellular, pressure-injection of d-myo-inositol 1,4,5 trisphosphate. At temperatures between 18 degrees C and 22 degrees C and with an extracellular calcium concentration of 10 mM, the responses of 4 cells to light and to injections of 100 microM inositol trisphosphate displayed average latencies of 71 and 56 ms, respectively. The latencies of responses to InsP3 included an estimated 20 ms dead-time inherent in the injection method. Reducing the temperature lengthened the latency of the response to light (Q10 approximately 3.2 between 7 and 22 degrees C) more than that to inositol trisphosphate (Q10 approximately 2.3). Bathing the photoreceptors in seawater containing no added calcium and 1 mM of the calcium chelator EGTA greatly increased the latency of the light response at all temperatures, but did not increase the latency of the response to inositol trisphosphate. We conclude that the response to inositol trisphosphate lacks the calcium- and temperature-sensitive latent period which characterizes the response to light. If inositol trisphosphate acts, via the release of stored calcium, to stimulate an intermediate in the visual cascade, then that intermediate would appear to be downstream from the latency-generating mechanism.

Aequorin↗
PubMed1992

Effects of capsaicin on cutaneous vasodilator responses in humans.

The neurovascular responses to noxious electrically evoked axon reflex (EAR) stimulation and iontophoretic application of endothelium-dependent [acetylcholine (ACh)] and independent [sodium nitrite (NaNO2)] vasodilator substances were examined in human forearm skin using laser Doppler flowmetry, before and after repeated topical applications of the neurotoxin capsaicin (chronic capsaicin pre-treatment). Following 3 or 4 days of capsaicin pre-treatment the normal vasodilator response to acute application of capsaicin was significantly reduced as was the EAR response. There were, however, no significant changes in the vasodilator responses to either ACh or NaNO2, suggesting that the neurogenic axon reflex is in series with the endothelial and microvascular smooth muscle mechanisms of vasodilatation. Recovery of normal EAR occurred within 2-4 weeks of cessation of capsaicin pre-treatment.

Adult↗
PubMed1992

Contouring structures for 3-dimensional treatment planning.

Three-dimensional (3-D) treatment planning is a labor-intensive process with contouring of the target volume and critical normal tissues being a significant time-consuming component. The use of 3-D treatment planning on a routine basis may be limited by the time required to complete treatment plans. Despite the need to increase the efficiency of the process, there is little literature addressing the speed and accuracy of contouring systems. In an attempt to initiate systematic analysis of the contouring process, data sets consisting of 10 CT images each were developed on two patients with esophageal carcinoma. Nine different operators manually contoured structures (target volume, spinal canal, lungs) on the data sets using four different contouring systems present in our department. These included both commercially available systems and those developed by the authors. There was a wide variation in the hardware and software characteristics of these systems. The time required to contour the CT data sets was recorded and analyzed. The contouring accuracy was assessed by comparison with a standard template derived from the CT data set for each image. The contouring time was found to be dependent on the system design, previous contouring experience, and the type of drawing instrument (lightpen vs mouse). The mean contouring time ranged from 26 minutes per patient for the fastest system to 41 minutes for the slowest. Potential clinically significant errors in contouring were rare for the spinal canal and lungs but present at a greater rate for the target volume (30.3%). The implications of this finding are discussed.

Adenocarcinoma↗
PubMed1992

Transdermal fentanyl: suggested recommendations for clinical use.

Transdermal fentanyl offers the advantage of providing continuous administration of a potent opioid in the absence of needles and expensive drug-infusion pumps for the treatment of cancer pain. When transdermal fentanyl is initiated, it may be necessary to change the dose every 24-48 hr until an appropriate dose is titrated to the needs of the patient. This should be done by providing short-acting opioids as rescue analgesics for breakthrough pain. Well-accepted principles established for chronic opioid use in cancer pain management should apply to the administration of transdermal fentanyl as well. These include dose titration, the coadministration of adjuvant drugs to counteract opioid side effects and enhance analgesia, and the need to reassess the patient continuously for recurrent tumor and other new sources of pain. Further clinically relevant studies are needed and include 1) the determination of the relative potency of transdermal fentanyl, especially in comparison with oral and parenteral morphine; 2) a prospective study of the side-effect profile of transdermal fentanyl in relationship to oral morphine; and 3) the role of oral transmucosal administration of fentanyl in selection of starting doses of transdermal fentanyl and as a means to provide rescue doses for breakthrough pain.

Administration, Cutaneous↗
PubMed1992

The management of intractable bone pain: a clinician's perspective.

Bone metastases occur in up to 85% of patients (at autopsy) who have breast, lung, and prostate cancer, and are a common cause of pain and neurological morbidity in patients with these and other cancers. The management of pain, the most common complication of bone metastasis, requires a knowledge of specific clinical syndromes and the associated neurological and orthopedic morbidities, as well as an understanding of current antitumor and pharmacological therapies. Knowledge of these potential complications are important in the design of clinical trials that seek to evaluate the effectiveness of new treatments for bone metastasis. Although radiation therapy in combination with analgesic drug therapies remains the mainstay of treatment, much recent interest in drugs with specific effects on bone elements, especially the osteoclast, offer the promise of providing effective pain relief with fewer side effects than is currently possible with conventional therapies.

Bone Neoplasms↗
PubMed1991

Motor functions in rat hindlimb muscles following neonatal sciatic nerve crush.

The sciatic nerve was crushed in the right hindlimb in newborn (3-8 h old) rats. Two to four months later, electromyographic activity was recorded from both the control and reinnervated ankle extensor muscles soleus or lateral gastrocnemius and from the ankle flexor muscle tibialis anterior. Tonic postural activity was present in the extensor muscles on both sides during quiet stance. The control flexor muscles were usually silent in this situation, but the reinnervated flexors exhibited abnormal sustained activity. During locomotion, the control extensors were activated during the stance phase and their mean burst made up 61.5% of the step cycle. The control tibialis anterior muscle fired only during the swing phase, with the burst lasting 18.1% of the step cycle. In the reinnervated extensor muscles, the mean burst duration was decreased (46% of the cycle) but the basic locomotor pattern was not impaired. The reinnervated tibialis muscle, however, was activated abnormally, with one appropriate flexor burst during the swing phase and an "extensor-like" burst during the stance phase of the step. Reflex responses to stretch were weak or absent on the operated side. Histological examination showed that the reinnervated soleus and tibialis muscles were almost devoid of muscle spindles. The motor unit mean firing rates in the reinnervated soleus (22 imp/s) and lateral gastrocnemius (45 imp/s) matched those of the control muscles (25 and 42 imp/s, respectively). In contrast to the phasic, high-frequency firing (52-80 imp/s) in the control tibialis, the reinnervated tibialis motor units fired at significantly lower rates (22-56 imp/s).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗