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Biomedical subjects

R Payne

Publications and source records attributed to R Payne.

At least 109 records · Page 6Linked to original sources
PubMed1991

Injection of inositol trisphosphorothioate into Limulus ventral photoreceptors causes oscillations of free cytosolic calcium.

Limulus ventral photoreceptors contain calcium stores sensitive to release by D-myo-inositol 1,4,5 trisphosphate (InsP3) and a calcium-activated conductance that depolarizes the cell. Mechanisms that terminate the response to InsP3 were investigated using nonmetabolizable DL-myo-inositol 1,4,5 trisphosphorothioate (InsPS3). An injection of 1 mM InsPS3 into a photoreceptor's light-sensitive lobe caused an initial elevation of cytosolic free calcium ion concentration (Cai) and a depolarization lasting only 1-2 s. A period of densensitization followed, during which injections of InsPS3 were ineffective. As sensitivity recovered, oscillations of membrane potential began, continuing for many minutes with a frequency of 0.07-0.3 Hz. The activity of InsPS3 probably results from the D-stereoisomer, since L-InsP3 was much less effective than InsP3. Injections of 1 mM InsP3 caused an initial depolarization and a period of densensitization similar to that caused by 1 mM InsPS3, but no sustained oscillations of membrane potential. The initial response to InsPS3 or InsP3 may therefore be terminated by densensitization, rather than by metabolism. Metabolism of InsP3 may prevent oscillations of membrane potential after sensitivity has recovered. The InsPS3-induced oscillations of membrane potential accompanied oscillations of Cai and were abolished by injection of ethyleneglycol-bis (beta-aminoethyl ether)-N,N'-tetraacetic acid. Removal of extracellular calcium reduced the frequency of oscillation but not its amplitude. Under voltage clamp, oscillations of inward current were observed. These results indicate that periodic bursts of calcium release underly the oscillations of membrane potential. After each burst, the sensitivity of the cell to injected InsP3 was greatly reduced, recovering during the interburst interval. The oscillations may, therefore, result in part from a periodic variation in sensitivity to a constant concentration of InsPS3. Prior injection of calcium inhibited depolarization by InsPS3, suggesting that feedback inhibition of InsPS3-induced calcium release by elevated Cai may mediate desensitization between bursts and after injections of InsPS3.

Animals↗
PubMed1991

Pain syndromes in the cancer patient.

Paraneoplastic syndromes affect the nervous system in a very small percentage of patients with cancer. In those patients, portions of the nervous system are damaged or destroyed, usually in association with a small and often occult neoplasm elsewhere in the body. Current evidence suggests that these syndromes occur when the body mounts an immune response to an antigen shared between the tumor and the nervous system. The immune attack is then misdirected against that portion of the nervous system that possesses the "onconeural" antigen.

Humans↗
PubMed1991

Spatial restriction of light adaptation and mutation-induced inactivation in fly photoreceptors.

The spatial spread within fly photoreceptors of 2 forms of desensitization by bright light have been investigated: the natural process of light adaptation in normal Musca photoreceptors and a receptor-potential inactivation in the no-steady-state (nss) mutant of the sheep blowfly Lucilia. The suction-electrode method used for recording from vertebrate rods was applied to fly ommatidia. A single ommatidium in vitro was partially sucked into a recording pipette. Illumination of the portion of the ommatidium within the pipette resulted in a flow of current having a wave form similar to that of the receptor potential and polarity consistent with current flow into the illuminated region of the photoreceptors. Two 5-microns slits of light, positioned at right angles to the ommatidial axis, were employed to determine the spread of light adaptation or inactivation along the ommatidium. The intensity of a flash of light delivered to one (adapting) slit was adjusted until it produced a criterion fractional reduction in the response to the other (test) slit. The reciprocal of this intensity of the adapting slit was taken as a measure of the effectiveness of the slit in causing light adaptation or inactivation. The effectiveness of the slit in causing light adaptation in normal Musca ommatidia fell as the adapting and test slits were moved farther apart along the ommatidial axis, declining to half its maximal value at a distance of 13 +/- 2 microns. Similar measurements of the effectiveness of a slit in causing light-induced inactivation in the nss mutant of Lucilia also demonstrated localization, declining to half its maximal value at a distance between the slits of 9 +/- 1 microns. Neither light adaptation nor inactivation by the nss mutation, therefore, appear to be mediated by voltage or by a highly diffusible agent. The results are consistent with the idea that inactivation by the nss mutation replaces adaptation in the mutant photoreceptors.

Adaptation, Physiological↗
PubMed1990

Feedback inhibition by calcium limits the release of calcium by inositol trisphosphate in Limulus ventral photoreceptors.

Injection of inositol 1,4,5 trisphosphate (InsP3) into Limulus ventral photoreceptors elevates the concentration of intracellular calcium ions and as a consequence depolarizes the photoreceptor. This InsP3-induced elevation can be inhibited by a prior injection of calcium or InsP3 delivered 1 s earlier. Recovery from this inhibition has a half-time of between 1.5 and 5 s at 20 degrees C. Calcium released by InsP3 therefore inhibits further release of calcium from InsP3-sensitive calcium stores. This feedback inhibition may protect the calcium stores from depletion during prolonged bright illumination. Feedback inhibition, rather than periodic depletion of calcium stores, may also underlie the oscillatory bursts of InsP3-induced calcium release that have been observed in many cell types.

Animals↗
PubMed1990

Medication-induced performance deficits: analgesics and narcotics.

Pain is the most common medical complaint, and analgesic drugs are often used for its management. Seven out of 10 Americans took nonprescription pain relievers in the last year. Analgesics are classified as nonnarcotics (acetaminophen, aspirin, and nonsteroidal anti-inflammatory drugs), narcotics (which include the morphine-like drugs), and analgesic adjuvants (a heterogeneous group of drugs, including antihistamines, phenothiazines, anticonvulsants, calcium channel blockers, and tricyclic antidepressants), which may have intrinsic analgesic efficacy for specific pain syndromes or may be used as co-analgesics in combination with the traditional nonnarcotic and narcotic agents. Although these agents can be used safely most of the time by patients with acute or chronic pain, all classes of analgesics may impair cardiovascular and neuropsychiatric functioning, which may influence job performance in specific instances.

Adjuvants, Pharmaceutic↗
PubMed1989

Cancer pain. Anatomy, physiology, and pharmacology.

Cancer pain can be divided into three classes: somatic, visceral, and deafferentation. Somatic and visceral pain result from activation of nociceptors by tumor infiltration of tissues and from secondary inflammatory changes with release of algesic chemicals that act to sensitize nociceptors. Pain may be experienced locally (somatic and visceral) or referred to remote cutaneous sites (visceral). Deafferentation pain results from injury to the nervous system due to tumor infiltration or cancer therapy and may persist even after the cause of the injury has been removed. Somatic, visceral, and deafferentation pain may be complicated by sympathetically maintained pain, in which efferent sympathetic activity promotes persistent pain, hyperpathia, and vasomotor and sudomotor changes after tissue injury from cancer or its therapy. The neurobiology of cancer pain is complex and incompletely understood. This article summarizes current knowledge in this area and briefly discusses approaches to cancer pain management that are based on this knowledge.

Animals↗
PubMed1989

On the dissociation constants of BAPTA-type calcium buffers.

We have determined or redetermined the calcium dissociation constants of seven BAPTA-type buffers with KD's in the range from 0.4 microM to about 20 mM in 300 mM KCl. These include four newly synthesized ones: 5-nitro BAPTA; 5,5'-dinitro BAPTA; 5-methyl-5'-nitro BAPTA; and 5-methyl-5'-formyl BAPTA. Moreover, we tabulate dissociation constants or KD's for BAPTA and eleven BAPTA-type buffers, compare most of them with an empirical curve based upon so-called Hammett values, and predict KD's for several still unsynthesized but potentially valuable buffers.

Buffers↗
PubMed1989

Pharmacologic management of bone pain in the cancer patient.

Cancer patients may experience acute or chronic pain caused by tumor infiltration of pain-sensitive structures or related to surgery, radiation, and chemotherapy. Acute bone pain, with or without associated neurologic deficits resulting from tumor metastasis to bone and contiguous neural structures (e.g., large peripheral nerve trunks or the spinal cord), is a common cause of intractable pain in cancer patients. Most often, treatment of bone pain involves the concomitant use of focal radiation therapy and analgesic drugs, especially steroids, nonsteroidal anti-inflammatory drugs (usually in combination with opioids), and adjuvant analgesic agents such as levodopa and calcitonin. However, pharmacologic therapy is not always efficacious and may have significant side effects. Less commonly, invasive therapies, such as resection of vertebral body tumor with spinal reconstruction or pituitary ablation and intraventricular opioid administration (for diffuse bone pain), are offered. In this article I discuss current approaches to the management of pain in cancer patients, emphasizing current hypotheses on the pathogenesis of bone pain and the rationale for its pharmacologic treatment.

Aged↗
PubMed1988

Leukemic relapse presenting as sciatic nerve involvement by chloroma (granulocytic sarcoma).

A relapse of acute nonlymphocytic leukemia in a child presented as subacute mononeuropathy involving the sciatic nerve. Surgical exploration showed a chloroma (granulocytic sarcoma) of the distal sciatic nerve, but resection and irradiation did not lead to recovery of nerve function or complete resolution of the patient's symptomatic neuropathic pain. This case represents a rare neurologic complication of what is currently an uncommon presentation for leukemic relapse, and may be the only reported case of chloromatous involvement of the peripheral nervous system (PNS) without coexisting epidural or leptomeningeal leukemia.

Child↗
PubMed1988

The localization of calcium release by inositol trisphosphate in Limulus photoreceptors and its control by negative feedback.

Microvillar photoreceptors of invertebrates exhibit a light-induced rise in the intracellular concentration of free calcium (Cai) that results in part from release of calcium from an intracellular compartment. This light-induced release of calcium appears to result from a cascade of reactions that involve rhodopsin, a GTP-binding protein and a phospholipase-C which releases inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) from the plasma membrane; the Ins(1,4,5)P3 acts to release calcium from smooth endoplasmic reticulum. In the ventral photoreceptor of the horseshoe crab Limulus polyphemus not all of the endoplasmic reticulum is subject to calcium release by Ins(1,4,5)P3. Only endoplasmic reticulum in the light-sensitive region of the cell is competent to release calcium in response to Ins(1,4,5)P3. The release of calcium by Ins(1,4,5)P3 in ventral photoreceptors appears to be subject to feedback inhibition through elevated Cai. We suggest that this feedback inhibition contributes to sensory adaptation in the photoreceptor and may account for oscillatory membrane responses sometimes observed with large injections of Ins(1,4,5)P3.

Animals↗
PubMed1988

The concentration of cytosolic free calcium in vertebrate rod outer segments measured with fura-2.

The use of fluorescent indicators such as fura-2 (Grynkiewicz et al., 1985) to measure the cytosolic free calcium activity in retinal rods is complicated by the rods' sensitivity both to the fluorescence and to the light that excites it. By stimulating fluorescence from large numbers of rods in whole, loaded retinas and averaging repeated measurements, however, we have been able to monitor changes in free [Ca2+]i during exposure to nonsaturating lights under physiological conditions. Retinas, isolated from the bullfrog Rana catesbeiana, were loaded with fura-2 by incubation and mounted, receptor-side up, in a perfusion chamber placed on the stage of a specially designed apparatus. A step of light delivered from above, whose wavelength alternated between 340 and 380 nm every 110 msec, excited fluorescence from 24 mm2 of retina and evoked a light response (the aspartate-isolated pIII component of the electroretinogram--ERG). By comparing the fluorescence intensities excited by the 2 wavelengths (corrected for background and dark-noise), the free [Ca2+]i of the rod outer segment was determined. In darkness, the [Ca2+]i of the outer segment was found to be approximately 220 nM. A bright light caused it to fall exponentially to approximately 140 nM, with a time constant of approximately 1.6 sec. The value of [Ca2+]i at the onset of illumination was independent of stimulus intensity over a 2 log-unit range, and in all cases the fall was monotonic. After terminating the illumination, [Ca2+]i rose again to its time-zero value.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1987

Anatomy, physiology, and neuropharmacology of cancer pain.

The anatomy, physiology, and pharmacology of nociception and its modification by analgesic drugs have been studied extensively in the past decade. Although the neural mechanisms of nociceptors and the stimuli that activate them are much better understood, it must be emphasized that the perception of pain, as well as the meaning of pain to the individual, is a complex behavioral phenomenon and involves psychologic and emotional processes in addition to activation of nociceptive pathways. Pain related to malignant disease can be classified as somatic, visceral, and deafferentation in type. Somatic pain and visceral pain involve direct activation of nociceptors and are often a complication of tumor infiltration of tissues or injury of tissues as a consequence of cancer therapy. The management of this type of pain is typically accomplished by treating the tumor (with surgery, chemotherapy, and/or radiation therapy) and by using the appropriate non-narcotic, narcotic, and adjuvant analgesic agents. Neuroablative therapies may be helpful in specific circumstances. For example, cordotomy may be helpful for unilateral pain below the waist in patients with somatic and visceral pain. This procedure may also be helpful for early deafferentiation pain (i.e., lumbosacral plexopathy) in which peripheral nerves are compressed but not infiltrated or destroyed by metastatic tumor growth. Deafferentiation pain may be a complication of tumor infiltration of peripheral nerve or of cancer therapy that injures neural tissue. This type of pain is often poorly tolerated and difficult to control, particularly if not treated early and aggressively. Although incompletely understood, the pathophysiology of deafferentation pain appears to be different from that of somatic or visceral pain, and the treatment approaches may be different. Management approaches to deafferentation pain usually emphasize treatment of the pain, because injury to the nervous system may be difficult to reverse, even if one can successfully treat the underlying malignancy, and many deafferentation pain syndromes occur as a complication of cancer therapy. The role of narcotic analgesics in the management of deafferentation pain is not clear, although the published experience suggests that they are less useful than in somatic or visceral pain.

Analgesia↗