Biomedical subjects

J del Castillo

Publications and source records attributed to J del Castillo.

At least 55 records · Page 3Linked to original sources

PubMed1989

The hematologic effects of chronic administration of the monokines tumor necrosis factor, interleukin-1, and granulocyte-colony stimulating factor on bone marrow and circulation.

Monokines may contribute to the regulation of hematopoiesis and circulating numbers of leukocytes during chronic inflammation. The hematologic effects of daily intravenous injection of the recombinant monokines tumor necrosis factor (TNF), interleukin-1 (IL-1), and granulocyte-colony stimulating factor (G-CSF) were therefore studied in the bone marrow and circulation of rats over the course of a week. TNF induced daily neutrophilia and lymphopenia with no evidence of tachyphylaxis. TNF also induced a slight decrease in early myeloid forms in the marrow, but, more strikingly, induced a marked erythroid hyperplasia of late normoblasts, although no changes other than a slight reticulocytosis were noted in the peripheral red blood cell compartment. IL-1 also induced daily neutrophilia and lymphopenia with no evidence of tachyphylaxis. IL-1 differed from TNF in the induction of a significant myeloid hyperplasia and in the lack of any effect on the erythroid elements of the marrow. The lack of tachyphylaxis to the chronic administration of both TNF and IL-1 suggests that the mechanism of endotoxin-induced tachyphylaxis is not at the level of the effector cell response to these endogenous cytokines. G-CSF induced a biphasic peripheral neutrophilia first peaking on day one, reaching a nadir on day 4, and then rising progressively again until day 7. The low level of neutrophilia on day 4 is not due to marrow depletion of neutrophils secondary to the neutrophil releasing activity of G-CSF because the marrows of G-CSF-treated rats on both days 3 and 7 contained over twice the number of mature neutrophils as controls. Thus, the trough in the neutrophilia induced by G-CSF is postulated to be due to an as-yet unidentified negative feedback mechanism that inhibits neutrophil release from the marrow.

Animals↗

PubMed1989

Endotoxin-induced cytokine gene expression in vivo. I. Expression of tumor necrosis factor mRNA in visceral organs under physiologic conditions and during endotoxemia.

Tumor necrosis factor (TNF) mRNA was detected by Northern blotting in whole-organ homogenates of the spleen, liver, kidney, lung, and small bowel in naive and saline-injected control rats, supporting the hypothesis that TNF mRNA is present in vivo in a preformed intracellular pool. TNF mRNA in endotoxin-treated rats as quantitated by densitometry of the ratio of TNF mRNA to actin mRNA in Northern blots was present in increased quantity in the liver, kidney, and lung (1.6-2.9 times over time zero levels) at 15 minutes and increased quantity in the spleen, liver, and kidney (1.3-1.9 times over time zero levels) at 30 minutes. The kinetics of endotoxin-induced TNF gene expression are consistent with the relatively transient peak of serum TNF protein levels reported by previous investigators to occur approximately 1 hour after injection of endotoxin. Because TNF mRNA appeared ubiquitous in the organs of control rats examined and because the endotoxin-induced increase in TNF mRNA was relatively small, endotoxin may induce the expression of the TNF protein in serum not only by increasing TNF mRNA levels but perhaps more importantly by a posttranscriptional mechanism. The presence of a preformed pool of TNF mRNA may teleologically be viewed as a mechanism to increase the rapidity of the host's response to sepsis.

Actins↗

PubMed1989

In vivo hematologic effects of recombinant interleukin-6 on hematopoiesis and circulating numbers of RBCs and WBCs.

Interleukin-6 (IL-6) administered as a single intravenous (IV) injection caused the following changes in the peripheral circulation of rats: (a) a biphasic neutrophilia with an initial peak at 1.5 hours and a second sustained wave of neutrophilia between four and 12 hours, (b) a mild lymphocytosis at 0.5 hours and a mild lymphopenia between 1.5 and four hours, and (c) a reticulocytosis between 12 and 24 hours. The bone marrow showed no significant changes at 1.5 hours, suggesting that the peripheral neutrophilia at that time is caused by demargination of intravascular neutrophils and not by release of marrow neutrophils. The bone marrow at 12 hours showed a mild left-shifted myeloid hyperplasia of myeloblasts and promyelocytes and a tremendous erythroid hyperplasia of intermediate and late normoblasts. The bone marrow at 24 hours showed a continued mild myeloid hyperplasia and striking erythroid hyperplasia. In conclusion, IL-6 in vivo acts as a stimulus for myelopoiesis and erythropoiesis and causes accompanying peripheral changes in the number of neutrophils, lymphocytes, and RBCs.

Animals↗

PubMed1989

Acute in vivo effects of IL-3 alone and in combination with IL-6 on the blood cells of the circulation and bone marrow.

Recombinant human IL-3 administered intravenously to rats as a single injection induced peripheral neutrophilia and monocytosis beginning at 4 to 6 hours after injection, peaking at 8 hours, and subsiding to normal by 12 to 24 hours. IL-3 did not induce an initial neutropenia such as accompanies endotoxin-, G-CSF-, and TNF-induced neutrophilia, or lymphopenia such as accompanies endotoxin-, IL-1-, and TNF-induced neutrophilia. The IL-3-induced peripheral neutrophilia was accompanied by a decrease in mature marrow neutrophils, indicating that the mechanism of neutrophilia was through marrow release rather than by demargination, which occurs after the administration of epinephrine or IL-6. The release of mature marrow neutrophils further suggests that IL-3 either has intrinsic neutrophil releasing activity or indirectly causes neutrophil release through the gene expression of a second cytokine. IL-3 induced a striking left-shifted myeloid hyperplasia in the bone marrow at 8 hours that morphologically was very similar to that observed after administration of endotoxin, a finding consistent with the hypothesis of previous investigators that endotoxin may in part act indirectly on hematopoietic cells by eliciting local marrow production of IL-3. Finally, IL-3 induced an increase in marrow pronormoblasts at 8 hours, consistent with the in vitro proliferative effect of IL-3 on erythroid stem cells. The combination of IL-3 and IL-6 induced a synergistic peripheral neutrophilia and monocytosis and a striking synergistic increase in marrow mast cells. The combination of IL-3 and IL-6 also induced an erythroid and left-shifted myeloid hyperplasia such as would be expected given the individual effects of these hematopoietic growth factors.

Animals↗

PubMed1988

The contributions of adrenal hormones, hemodynamic factors, and the endotoxin-related stress reaction to stable prostaglandin analog-induced peripheral lymphopenia and neutrophilia.

Stable prostaglandin analogs are known to induce lymphopenia and neutrophilia in a dose-dependent fashion after subcutaneous injection in rats. The purpose of the present investigation is to determine whether the prostaglandin-induced changes in circulating leukocytes might be secondary to hypotension with the ensuing release of adrenal hormones. The adrenal medullary catecholamine epinephrine was found to induce neutrophilia in both intact and adrenalectomized rats, and the glucocorticosteroid analog dexamethasone induced a profound lymphopenia in rats as reported by previous investigators. A stable analog of PGF2 alpha (15-S-15-methyl PGF2 alpha; M-PGF2 alpha) at the dose of 1 mg/kg induced marked systemic hypotension 1 h after injection, with lymphopenia and neutrophilia 6 h after injection. The non-prostanoid hypotensive agent captopril, at a dose of 63 mg/kg, induced a hypotension of similar magnitude and kinetics to that induced by prostaglandin. Captopril also induced lymphopenia and neutrophilia at 6 h, although the neutrophilia was of lesser magnitude than that induced by prostaglandins. The prostaglandin-induced lymphopenia was found to be mediated, at least in part, by the hypotension-induced release of adrenal hormones, as evidenced by the abrogation of lymphopenia in prostaglandin-treated adrenalectomized rats. Captopril-treated adrenalectomized rats, however, did develop a significant lymphopenia, suggesting that hypotension can result in lymphopenia even in adrenalectomized rats. The M-PGF2 alpha-induced neutrophilia in adrenalectomized rats, by comparison to captopril-induced neutrophilia in adrenalectomized rats, was greater than the neutrophilia expected as the result of hypotension alone. Indeed, the M-PGF2 alpha-induced neutrophilia in adrenalectomized rats was greater than the captopril-induced neutrophilia in sham-adrenalectomized rats. Thus, a portion of the neutrophilia induced by M-PGF2 alpha in intact rats may be mediated through adrenal-independent, hemodynamic-independent mechanisms. The possibility that M-PGF2 alpha might be inducing neutrophilia via an endotoxin-like stress reaction was investigated by examining changes in circulating white blood cells in intact and adrenalectomized C3H/HeN (endotoxin-sensitive) and C3H/HeJ (endotoxin-resistant) mice after prostaglandin administration. No quantitative differences in the prostaglandin-induced neutrophilia were noted in C3H/HeJ mice as compared to the C3H/HeN mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗

PubMed1988

Non-desensitizing in vitro anaphylactic reaction of chicken visceral muscle.

1. The contractions elicited in pieces of small intestine of actively immunized young chickens upon exposure to the specific antigen (Ag), or Schultz-Dale reaction, have been compared to similar responses of sensitized guinea-pig intestine. 2. Guinea-pig intestine responds, typically, with a large contraction to the first application of Ag. This is followed by a spontaneous relaxation of the preparation, while still in the presence of the Ag, and a rapid desensitization; i.e. further exposures to Ag fail to evoke new contractions. 3. In marked contrast, chicken intestine responds to the Ag with a contraction that remains at its maximal initial value for ca 5 min and then declines only slowly. 4. Exposure to the Ag does not desensitize chicken intestine, which relaxes upon washing out the antigenic protein but contracts again when this is re-introduced in the bath. 5. In addition, consecutive Schultz-Dale reactions of chicken intestine showed a consistent potentiation. They reached a maximal amplitude when the tissue was exposed to the Ag 5-7 times. Such a potentiation is abolished by storing the preparations for 24 hr at 4 degrees C. 6. These observations are discussed in terms of the known properties of avian antibodies.

Acetylcholine↗

PubMed1988

Kinetics and mechanisms of recombinant human granulocyte-colony stimulating factor-induced neutrophilia.

Recombinant human granulocyte colony stimulating factor (G-CSF) injected intravenously in rats causes an initial peripheral neutropenia between 3 and 15 minutes and a subsequent neutrophilia beginning at 0.5 hours, peaking between 12 and 24 hours, and subsiding to normal between 30 and 36 hours. A striking hypersegmentation of neutrophil nuclei is observed between 30 and 48 hours. The bone marrow at 4 and 12 hours exhibits an increase in number, mitoses, size, and cytoplasmic granulation of myeloblasts and promyelocytes but a decrease in mature neutrophils, demonstrating that G-CSF acts not only as a mitogen and growth factor for early cells in the myeloid series but also as a releasing factor for mature marrow neutrophils. The bone marrow at 48 hours contains slightly increased numbers of myelocytes and metamyelocytes and large numbers of hypersegmented neutrophils. Dexamethasone and gamma-interferon inhibit the magnitude of G-CSF-induced neutrophilia, suggesting that endogenous glucocorticosteroids and gamma-interferon, both which are released along with G-CSF in vivo during endotoxemia, may play a negative feedback role in the endogenous regulation of granulopoiesis. G-CSF may act in concert with other monokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1) to induce the changes in circulating numbers of leukocytes noted during endotoxemia.

Animals↗

PubMed1987

Kinetics and mechanisms of recombinant human interleukin 1 and tumor necrosis factor-alpha-induced changes in circulating numbers of neutrophils and lymphocytes.

Human recombinant interleukins 1 alpha and 1 beta (rIL-1 alpha and -1 beta) both induced monophasic peripheral neutrophilia and lymphopenia in Lewis rats 1.5 hr after i.v. injection. The kinetics of rIL-1 alpha- and -1 beta-induced neutrophilia were similar to those induced by human monocyte-derived IL-1, IL-1 alpha, and IL-1 beta, and the peripheral neutrophilia was accompanied by a marked decrease in marrow neutrophils. Arachidonic acid metabolites are implicated as biochemical intermediates in the production of the neutrophilia but not lymphopenia, since indomethacin and dexamethasone both completely abrogated IL-1-induced neutrophilia but did not affect the IL-1-induced lymphopenia. Acetylsalicylic acid, a cyclooxygenase inhibitor, did not inhibit IL-1-induced neutrophilia, suggesting that products of the lipoxygenase rather than the cyclooxygenase pathway of arachidonate metabolism may contribute to the neutrophilia. Human recombinant tumor necrosis factor-alpha (rTNF) administered i.v. to Lewis rats induced peripheral neutropenia, two peaks of neutrophilia, and lymphopenia. A wide range of doses of rTNF resulted in an initial neutropenia at 0.5 hr after injection followed by a first peak of neutrophilia at 1.5 hr and a second peak of neutrophilia at 6 hr. The initial neutropenia and the first peak of neutrophilia were not inhibited by pretreatment of rats with dexamethasone, indomethacin, or aspirin. The second peak of neutrophilia was inhibited by both dexamethasone and indomethacin, but was not at all inhibited by aspirin, suggesting that the second peak of neutrophilia is mediated by the release of endogenous cytokines, especially by IL-1, since exogenous IL-1-induced neutrophilia is also completely inhibited by dexamethasone and indomethacin but not by aspirin. The TNF-induced peripheral neutrophilia is also accompanied by a significant depletion of bone marrow neutrophils, indicating that the source of increased circulating neutrophils is, at least in part, via recruitment of marrow neutrophils. Systemic blood pressure was not affected by IL-1 or rTNF at the dosages employed, showing that the changes in circulating leukocyte subsets were not attributable to hemodynamic changes nor to the hemodynamic change-related release of adrenal hormones. Adrenalectomy did not alter the IL-1- or rTNF-induced neutrophilia or lymphopenia, also demonstrating that neither monokine mediates its hematologic effects on peripheral blood leukocytes via the release of adrenal hormones.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1987

Barium spikes are generated in the spines of the sea urchin Diadema antillarum.

In the presence of calcium, Ba2+ ions, at concentrations as low as 1-2 mM, block the action potentials (a.p.'s) elicited by the electrical stimulation of the primary spines of Diadema antillarum. Lower concentrations of barium (0.1 mM) potentiate the a.p.'s recorded from spines equilibrated with Ca-Free artificial sea water (ASW). Exposure of the spines to a saturated solution of EDTA in Ca-free, unbuffered ASW reversibly blocks their electrical activity. Spines blocked by EDTA continue to generate a.p.'s following their equilibration with Ca-free ASW containing 1 mM of Ba2+ ions. The time course of the a.p.'s recorded from spines equilibrated with normal ASW is only slightly affected by the combined action of 15 mM of tetraethylammonium (TEA) and 5 mM of 4-aminopyridine (4-AP). In contrast, the duration of the a.p.'s recorded from spines blocked by EDTA and placed in 1 mM barium is markedly increased by the combined actions of TEA and 4-AP at the above concentrations. We conclude that the Ca-channels of the neurites present in Diadema spines are not, at least qualitatively, an exception with regard to their permeation by Ba2+. The blocking action of low concentrations of these ions, particularly in the presence of calcium, may be explained by the extremely high surface to volume ratio prevailing in neurites with a diameter of only less than 0.1-0.3 micron.

4-Aminopyridine↗

PubMed1987

Recombinant human alpha lymphotoxin (tumor necrosis factor-beta) induces peripheral neutrophilia and lymphopenia in the rat.

Recombinant human alpha lymphotoxin (rLT) administered intravenously to Lewis rats induces peripheral neutrophilia and lymphopenia in a dose-response dependent fashion. A dose of 30,000 units of rLT induced a neutrophilia (1589 +/- 326 to 5554 +/- 1050 neutrophils/cu mm) and lymphopenia (10,368 +/- 992 to 4636 +/- 878 lymphocytes/cu mm) at 2 hours after injection that was highly significant (P less than 0.001 and P less than 0.001, respectively) in comparison with vehicle controls. The kinetics of the neutrophilia that peaked at 2 hours as well as of the lymphopenia were highly reminiscent of the neutrophilia and lymphopenia following intravenous administration of either recombinant human interleukin-1 (IL-1) alpha or beta to rats. The peripheral neutrophilia was accompanied by a significant depletion of bone marrow neutrophils (P less than 0.001), as is also known to occur after administration of IL-1. Systemic blood pressure was not affected by rLT, which suggested that the changes in circulating leukocyte subsets were not attributable to hemodynamic changes nor to the hemodynamic-change-related release of adrenal hormones. Adrenalectomy did not alter the rLT-induced neutrophilia or lymphopenia, which suggested that rLT does not mediate its hematologic effects on peripheral blood leukocytes via the release of adrenal hormones. Pretreatment of rats with dexamethasone, indomethacin, or aspirin also did not alter rLT-induced neutrophilia or lymphopenia, which suggested that rLT-induced hematologic effects were not mediated via arachidonic acid metabolites, in stark contrast to IL-1 induced neutrophilia, which is inhibited by both dexamethasone and indomethacin.

Animals↗

PubMed1985

Some properties of the action potentials conducted in the spines of the sea urchin Diadema antillarum.

Brief (2-5 msec) electrical pulses applied to the primary spines of the sea urchin Diadema antillarum elicit graded action potentials (ap's). These ap's can be attributed to the electrical activity of a set of 14-21 bundles of neurites, each comprising 1000 processes near the spine base and tapering towards the spine tip. The shape of the ap's varies from a simple diphasic deflection to a complex waveform with 6 or more components. Peak-to-peak amplitude is less than 1mV. The ap's are conducted at a uniform speed of ca. 27 cm/sec. The ap's are not affected by tetrodotoxin (1 microgram/ml) and continue to be produced in Na-free artificial sea water (ASW). The amplitude of the ap's is greatly reduced or totally abolished in Ca-free ASW. However, some electrical activity may continue in the absence of external Ca, due to release of Ca2+ ions from the calcium carbonate crystals of the spine shaft. Replacing the Ca content of ASW by barium ions causes an irreversible blockade of the ap's. Spines equilibrated with ASW containing Sr2+ ions instead of Ca2+ produce ap's of increased amplitude (up to X 2). The ap's are blocked by La3+, Co2+, Cd2+ (2-5 mM) and by the organic Ca channel blocker Bepridil (2 mM). We conclude that the spinal ap's are due to the summation of Ca spikes produced by the activation of Ca channels which are blocked by barium and have a high affinity for, or permeability to Sr vs Ca.

Action Potentials↗

PubMed1985

Generation of calcium action potentials in crustacean muscle fibers following exposure to sulfhydryl reagents.

The ventroabdominal flexor muscles of the crustacean Atya lanipes, which are normally completely inexcitable, generate trains of overshooting calcium action potentials after exposure to the sulfhydryl reagents known as alpha, beta-unsaturated carbonyl compounds. The chemically induced action potentials are abolished by protein reagents specific for guanidino and amino groups. Attempts to induce excitability by the use of agents that block potassium conductance were without success. It is proposed that calcium channels are made functional by the covalent modification of a calcium protochannel, via the interaction between the introduced carbonyl group and existing arginine residues.

Action Potentials↗

PubMed1985

Nerves in the spine of a sea urchin: a neglected division of the echinoderm nervous system.

Electrical stimulation of the primary spines (greater than 10 cm long) of the tropical sea urchin Diadema antillarum elicits graded compound action potentials that are conducted at a constant speed of approximately equal to 27 cm/sec. Ion substitution experiments suggest that these are due to the summation of calcium spikes. Structural studies have revealed the presence of up to 21 regularly disposed nerves within the spine shaft, each nerve bundle including greater than 1000 neurites in the basal region, narrowing to slender groups of processes near the spine tip. The neurites in each nerve range in diameter from less than 0.1- approximately equal to 2 micron. Most appear to be distal processes of presumed sensory perikarya situated at the level of the tissue cone surrounding the spine base, or more proximally, although some neurites may arise from perikarya near the spine tip. These nerve tracts are thought to correspond to the nerve fibers described by Hamann [(1887) Jena Z. Naturwiss. 21, 114-176] almost a century ago in spines of Centrostephanus longispinus and, thus, to represent a long-neglected region of the echinoid nervous system.

Action Potentials↗

PubMed1985

Succinyl derivatives of N-tris (hydroxymethyl) methyl-2-aminoethane sulphonic acid: their effects on the frog neuromuscular junction.

Succinic anhydride (SA) dissolved in Ringer solution buffered with N-tris (hydroxymethyl) methyl-2-aminoethane sulphonic acid (SA-TES solution) potentiates the depolarizing action of acetylcholine (ACh, 10-40 microM) on frog muscle and the tension induced by bath application of this agonist. Applied from one side of a double-barrelled micropipette, SA-TES increases the amplitude of iontophoretically elicited ACh potentials. The potentiation of the effects of ACh by SA-TES does not involve changes in either the activity of the ACh esterase or the input resistance of the muscle membrane. For depolarizations of frog sartorius muscle, dose-response relationships obtained for ACh concentrations from 0.5 to 20 microM indicate that SA-TES increases the apparent affinity of ACh by a factor of 3. SA-TES exerts an "accelerating' effect on the responses elicited by bath-applied ACh; i.e., it increases the rate of depolarization when ACh is added to the bath and the rate of repolarization upon washing out. These effects are particularly marked in preparations treated with neostigmine (3 microM). SA-TES does not potentiate the depolarizing action of agonists which do not contain an ester group. Moreover, the time course of the responses elicited by these compounds is not influenced by SA-TES. SA-TES fails to influence significantly the effects of the neurally released transmitter. Only a 10% increase in the average amplitude of the endplate potentials was observed. SA hydrolyzes in about 30 min at room temperature; however the SA-TES solution retains its activity for several weeks. Succinate is inactive, and so is SA in Ringer buffered with phosphate. The SA-TES solution contains seven succinyl-TES derivatives, which were separated by ion-exchange chromatography and paper chromatography. At concentrations between 1 to 150 microM, these succinyl-TES derivatives affected the ACh-induced contraction of frog rectus abdominus muscle. The most abundant derivative potentiated the action of high doses of ACh, but was inhibitory at lower ones. The other derivatives were mostly inhibitory. These results are discussed in terms of two hypotheses. One postulates the presence of a diffusion barrier formed by groups that bind ACh and are saturated by SA-TES. The other assumes that SA-TES acts directly on the ACh receptor exerting its potentiating effect through a cooperative mechanism.

Acetylcholine↗

PubMed1983

Correlation of agonist structure with acetylcholine receptor kinetics: studies on the frog end-plate and on chick embryo muscle.

The apparent lifetimes of frog end-plate channels activated by several nicotinic agonists have been determined with voltage-jump and fluctuation analysis techniques. The agonists were monoquaternary, N-substituted derivatives of trimethylammonium (TMA). Methyl TMA activated channels which had apparent lifetimes about 3-4 times shorter than acetylcholine (ACh)-activated channels. This result was confirmed with single-channel recordings from embryonic chick skeletal muscle. Channel conductance and voltage dependence of channel lifetime were similar for methyl TMA- and ACh-activated channels. Methyl TMA showed no signs of blocking open end-plate channels. Ethyl TMA, acetylthiocholine, cholinethiol and carbamylcholine all activated channels similar to methyl TMA-activated channels with regard to lifetime. None of these agonists appeared to block end-plate channels in the employed concentrations. 4-ketopentyl TMA, which contains a methylene group in place of the ether oxygen of ACh, sometimes opened end-plate channels with similar apparent lifetimes as those opened by ACh. Single-channel recordings showed that bursts of current from channels activated by 4-ketopentyl TMA have similar durations as do those activated by ACh. Pentyl TMA and benzyl TMA block open end-plate channels even when delivered at doses which elicit very small currents. It is concluded that the ester moiety of ACh serves to stabilize the open conformation of the channel.

Acetylcholine↗

PubMed1982

Inhibitory action of high formamide concentrations on excitation-contraction coupling in skeletal muscle.

Strips of guinea pig ileum lose over 70% of their contractility when bathed in Krebs-Ringer solution containing 0.4-0.9 M formamide (FMD). This effect is not accompanied by an appreciable loss of tissue water and is totally reversed by washing the preparation in normal solution. Frog sartorius muscles also paralyze when immersed in Ringer containing FMD, but higher concentrations (1.0-2.0 M) and longer exposure times are required. Contractility is not recovered upon transferring these muscles to normal Ringer. However, the contractile proteins still respond to activator calcium as shown by the fact that these muscles still contract in the presence of caffeine. The membrane of muscles uncoupled by FMD retain electrical excitability, and neuromuscular transmission appears to be unimpaired. However, alterations in the early after-potential of the spikes suggest the occurrence of a sarcotubular disruption. Therefore, FMD appears to exert two separate effects on muscle: a reversible inhibition of contractility, as observed in ileal strips and an irreversible blockade due to an osmotic shock observed when frog muscles are returned to normal Ringer. The reversible effect is probably related to interference with the availability of activator calcium, since no marked inhibitory effects on the activities of the actomyosin-like and the calcium-dependent and -independent ATPases could be observed on FMD-treated subcellular fractions.

Adenosine Triphosphatases↗

PubMed1982

Automatic control of potential and agonist-induced current across the endplate membrane by drug electrophoresis.

Two techniques are described that are designed to elicit long and constant postsynaptic depolarizations or agonist-induced currents by the electrophoretic application of agonists to endplate membranes. In the first technique, which can be described as a "pharmacologic voltage clamp," the current flowing through the agonist pipette is controlled by the potential across the endplate membrane. Sustained depolarizations of constant amplitude can be obtained in this manner, while the agonist current needed to produce and maintain the response is recorded. The second technique uses a signal proportional to the current flowing across a voltage-clamped endplate membrane to control the delivery of agonist. This allows control of the intensity of the agonist-induced current. The possible application of these techniques in studying receptor desensitization and obtaining samples of post-synaptic current noise for spectral analysis is discussed.

Animals↗

PubMed1979

The Frenchman's fibular fracture (Maisonneuve fracture).

Two patients with injuries to the ankle sustained by rotational trauma complained only of pain in the ankle. Careful examination revealed tenderness over the proximal fibula. Subsequent radiographic studies revealed high helical fracture of the fibula, as originally described by Maisonneuve. The Maisonneuve fracture is produced by diastasis - a separation of bones resulting from rupture of ligaments around the ankle. According to classification of fibula injuries by mechanism of injury, the Maisonneuve fracture is due to external rotation of the foot relative to the tibia but it is not clear whether the foot is in pronation or supination or moves during injury.

Adult↗