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R L Moss

Publications and source records attributed to R L Moss.

At least 145 records · Page 8Linked to original sources
PubMed1991

Substitution of cardiac troponin C into rabbit muscle does not alter the length dependence of Ca2+ sensitivity of tension.

1. The isometric length-tension relationship for cardiac muscle is generally steeper than for skeletal muscle in the physiological range of sarcomere lengths. Recent studies suggest that cardiac troponin C (cTnC) may have intrinsic properties that confer greater length-dependent changes in Ca2+ sensitivity of tension than for skeletal troponin C (sTnC). We tested this hypothesis by characterizing tension-pCa (pCa is -log[Ca2+]) relationships in rabbit skinned psoas muscle fibres at mean sarcomere lengths of 2.32 and 1.87 microns both before and after partial replacement of endogenous sTnC with cTnC. 2. In untreated control fibres, the mid-point (pCa50) of the tension-pCa relationship shifted to lower pCa by 0.15 +/- 0.02 pCa units, i.e. became less sensitive to Ca2+, when sarcomere length was reduced, and the relationship became steeper. 3. Partial extraction of endogenous sTnC and reconstitution with cTnC resulted in no change in the length-dependent shift of pCa50 when reconstitution with cTnC was more than 95% complete; however, when reconstitution was less than 95% complete, there were significant increases in the length-dependent shift in pCa50. 4. An increase in the length-dependent shift of pCa50 was also observed in fibres from which sTnC was partially extracted, but no cTnC was subsequently re-added. 5. We conclude that differences in type of TnC alone are not sufficient to explain differences between skeletal and cardiac muscles in the length dependence of Ca2+ sensitivity of tension.

Animals↗
PubMed1990

Calcium-sensitive cross-bridge transitions in mammalian fast and slow skeletal muscle fibers.

The fundamental mechanism underlying the differing rates of tension development in fast and slow mammalian skeletal muscle is still unknown. Now, in skinned (membrane-permeabilized) single fibers it has been shown that the rate of formation of the strongly bound, force-producing cross-bridge between actin and myosin is calcium-sensitive in both fast and slow fibers and that the rate is markedly greater in fast fibers. The transition rates obtained at high calcium concentrations correlated with myosin isoform content, whereas at low calcium concentrations the thin filament regulatory proteins appeared to modulate the rate of tension development, especially in fast fibers. Fiber type-dependent differences in rates of cross-bridge transitions may account for the characteristic rates of tension development in mammalian fast and slow skeletal muscles.

Actins↗
PubMed1990

Electrophysiological actions of luteinizing hormone-releasing hormone: intracellular studies in the rat hippocampal slice preparation.

The electrophysiological effects of luteinizing hormone-releasing hormone (LHRH) on CA1 pyramidal cells were investigated utilizing intracellular recordings from the in vitro rat hippocampal slice preparation. Bath application of LHRH (10(-7) - 10(-12) M) resulted in several changes in the electrophysiological properties of CA1 neurons. LHRH induced a long-lasting depolarization associated with increased input resistance, a decrease in the afterhyperpolarization (AHP) following a train of action potentials, and a reduction in accommodation of repetitive cell discharge. These effects were blocked by the synthetic LHRH antagonist [Ac-delta-Pro1,pCl-D-Phe2,D-Trp3,6]-LHRH. These findings provide electrophysiological evidence for the role of LHRH as a neurotransmitter/neuromodulator in the hippocampus.

Action Potentials↗
PubMed1990

Electrophysiological identification of a pathway from the septal area to the medial amygdala: sensitivity to estrogen and luteinizing hormone-releasing hormone.

Medial amygdala neurons responsive to electrical stimulation of the medial septal area were electrophysiologically identified in ovariectomized, urethane-anesthetized female rats. Peristimulus time histograms were collected and used to define the orthodromic response. The action of iontophoretically applied luteinizing hormone-releasing hormone (LHRH) and an LHRH fragment, Ac-LHRH5-10, on the activity of orthodromically responsive neurons was tested. Of a total of 187 neurons recorded, 119 were identified as orthodromically responsive. Three types of orthodromic responses were observed: excitatory, inhibitory, and complex. Priming the animals with 5 micrograms estradiol benzoate (EB) 48 hr prior to recording had no effect on the overall number of neurons responding to septal area stimulation, but EB priming did significantly reduce the percentage of orthodromically excited neurons. The firing rate of the majority of amygdala neurons responsive to septal area stimulation was not affected by iontophoretically applied LHRH (59 of 76) or LHRH fragment (41 of 65). In some cases, application of LHRH (10 of 76) or Ac-LHRH5-10 (12 of 55) produced a change in neuronal firing that was similar in direction to the orthodromically evoked response. When applied during the collection of peristimulus time histograms, both peptides were also able to modulate the orthodromically evoked response (five of 18 cells tested with LHRH and three of 14 cells tested with Ac-LHRH5-10). The results demonstrate a large projection from the septal area to the amygdala, one component of which is altered by estrogen priming.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMed1990

Progress towards boron neutron capture therapy at the High Flux Reactor Petten.

During 1988 the first positive steps were taken to proceed with the design and construction of a neutron capture therapy facility on the High Flux Reactor (HFR) at Petten. The immediate aim is to realise within a short time (summer 1989), an epithermal neutron beam for radiobiological and filter optimisation studies on one of the 10 small aperture horizontal beam tubes. The following summer, a much larger neutron beam, i.e., in cross section and neutron fluence rate, will be constructed on one of the two large beam tubes that replaced the old thermal column in 1984. This latter beam tube faces one whole side of the reactor vessel, extending from a 50 x 40 cm input aperture to a 35 x 35 cm exit hole. The radiotherapeutic facility will be housed here, with the intention to start clinical trials at the beginning of 1991. This paper describes the present status of the project and includes: a general description of the pertinent characteristics with respect to NCT of the HFR; results of the recently completed preliminary neutron metrology and computer modeling at the input end of the candidate beam tube; the structure and planning of the proposed Work Programme; and the respective direct and indirect participation and collaboration with the Netherlands Cancer Institute and the European Collaboration Group on BNCT.

Animals↗
PubMed1990

Management of enterovesical fistulas.

The records of 51 patients diagnosed with enterovesical fistulas at Virginia Mason Medical Center from 1974 to 1988 were reviewed. Diverticulitis (41%), Crohn's disease (17%), and colorectal cancer (16%) were the major causes. In 50 of 51 patients, the diagnosis was made on the basis of the clinical history and the urine culture. Radiologic and endoscopic studies failed to identify the fistula in 20%, though all were confirmed at operation or autopsy. In four of eight patients with fistulas secondary to colorectal cancer, malignancy was not diagnosed preoperatively. Operation was performed in 84% of the patients. One-stage resection of the bowel was performed in 66% of patients with the intent of removing the fistula. The complication rate was 8% with no deaths. All multi-stage procedures were performed for fistulas complicated by abscess or bowel obstruction. There were two postoperative deaths in patients with metastatic cancer undergoing palliative diversion. All eight patients treated by diverting colostomy had persistent fistulas and urinary sepsis. All eight patients treated with antibiotics but without operation were free of complications of the fistula until death from other causes. Enterovesical fistula is a clinical diagnosis. Preoperative studies should be used to delineate the bowel disease and search for malignancy rather than to see the fistula, which is clinically apparent. One-stage resection of the involved bowel is the procedure of choice in the absence of abscess or bowel obstruction. When resection is not feasible, medical management with antibiotics is preferable to colostomy.

Adult↗
PubMed1990

Effects of partial extraction of light chain 2 on the Ca2+ sensitivities of isometric tension, stiffness, and velocity of shortening in skinned skeletal muscle fibers.

Various functional roles for myosin light chain 2 (LC2) have been suggested on the basis of numerous and predominantly in vitro biochemical studies. Using skinned fibers from rabbit psoas muscle, the present study examines the influence of partial removal of LC2 on isometric tension, stiffness, and maximum velocity of shortening at various levels of activation by Ca2+. Isometric tension, stiffness, and velocity of shortening were measured at pCa values between 6.6 and 4.5 (a) in a control fiber segment, (b) in the same fiber segment after partial removal of LC2, and (c) after recombination with LC2. The extraction solution contained 20 mM EDTA, 20 or 50 mM KCl, and either imidazole or PO4(2-) as a pH buffer (pH 7.0). The amount of LC2 extracted varied with the temperature, duration of extraction, and whether or not troponin C (0.5 mg/ml) was added to the extraction solution. Extraction of 20-40% LC2 resulted in increased active tensions in the range of pCa's between 6.6 and 5.7, but had no effect upon maximum tension. The tension-pCa relationship was left-shifted to lower [Ca2+] by as much as 0.2 pCa units after LC2 extraction. At low concentrations of Ca2+, an increase in stiffness proportional to the increase in tension was observed. Readdition of LC2 to these fiber segments resulted in a return of tension and stiffness to near control values. Stiffness during maximal activation was unaffected by partial extraction of LC2. LC2 extraction was shown to uniformly decrease (by 25-30%), the velocity of shortening during the high velocity phase but it did not significantly affect the low velocity phase of shortening. This effect was reversed by readdition of purified LC2 to the fiber segments. On the basis of these findings we conclude that LC2 may modulate the number of cross-bridges formed during Ca2+ activation and also the rate of cross-bridge detachment during shortening. These results are consistent with the idea that LC2 may modulate contraction via an influence upon the conformation of the S1-S2 hinge region of myosin.

Animals↗
PubMed1990

The effect of altered temperature on Ca2(+)-sensitive force in permeabilized myocardium and skeletal muscle. Evidence for force dependence of thin filament activation.

The effect of changes in temperature on the calcium sensitivity of tension development was examined in permeabilized cellular preparations of rat ventricle and rabbit psoas muscle. Maximum force and Ca2+ sensitivity of force development increased with temperature in both muscle types. Cardiac muscle was more sensitive to changes in temperature than skeletal muscle in the range 10-15 degrees C. It was postulated that the level of thin filament activation may be decreased by cooling. To investigate this possibility, troponin C (TnC) was partially extracted from both muscle types, thus decreasing the level of thin filament activation independent of temperature and, at least in skeletal muscle fibers, decreasing cooperative activation of the thin filament as well. TnC extraction from cardiac muscle reduced the calcium sensitivity of tension less than did extraction of TnC from skeletal muscle. In skeletal muscle the midpoint shift of the tension-pCa curve with altered temperature was greater after TnC extraction than in control fibers. Calcium sensitivity of tension development was proportional to the maximum tension generated in cardiac or skeletal muscle under all conditions studied. Based on these results, we conclude that (a) maximum tension-generating capability and calcium sensitivity of tension development are related, perhaps causally, in fast skeletal and cardiac muscles, and (b) thin filament activation is less cooperative in cardiac muscle than in skeletal muscle, which explains the differential sensitivity of the two fiber types to temperature and TnC extraction. Reducing thin filament cooperativity in skeletal muscle by TnC extraction results in a response to temperature similar to that of control cardiac cells. This study provides evidence that force levels in striated muscle influence the calcium binding affinity of TnC.

Actin Cytoskeleton↗
PubMed1990

Effects of tension and stiffness due to reduced pH in mammalian fast- and slow-twitch skinned skeletal muscle fibres.

1. The pH dependence of the Ca2+ sensitivities of isometric tension and stiffness was investigated at 10 and 15 degrees C in skinned single fibres from rat and rabbit fast- and slow-twitch skeletal muscles. Stiffness was determined by recording the tension responses to sinusoidal length changes (3.3 kHz); peak-to-peak amplitude of the length change was monitored by laser diffraction and averaged approximately 1.3 nm (half-sarcomere)-1. We have assumed that stiffness provides a measure of the number of cross-bridge attachments to actin. 2. At maximal Ca2+ activation, stiffness was depressed by 22 +/- 2% (mean +/- S.E.M.) in fast-twitch fibres but was unchanged in slow-twitch fibres when pH was lowered from 7.00 to 6.20. As reported previously, maximum tension was depressed by 20-45% at low pH, with the effect being greater in fast-twitch compared to slow-twitch fibres. 3. In fast-twitch fibres at 10 and 15 degrees C the Ca2+ concentrations for half-maximal activation of tension and stiffness were increased at low pH. In slow-twitch fibres, similar effects were observed at 15 degrees C, but at 10 degrees C there were no changes in the Ca2+ sensitivities of tension and stiffness when pH was lowered. 4. Linear relationships between relative tension and relative stiffness were obtained at all temperatures, with slopes of 1.04 +/- 0.01 at pH 7.00 and 0.76 +/- 0.01 at pH 6.20 in fast- and slow-twitch fibres, indicating that force per cross-bridge attachment is similarly reduced at low pH in both types of fibres. 5. In both fast- and slow-twitch fibres, rigor tension (no added ATP or creatine phosphate; pCa 9.0) was depressed by 35 +/- 7% and stiffness by 12 +/- 4% when pH was reduced from 7.00 to 6.20. Since cross-bridge cycling is inhibited in rigor the effect of low pH to depress rigor tension suggests that pH directly modulates the strength of the bond formed between actin and myosin. 6. The effect of low pH to reduce the apparent number of cross-bridge attachments during maximal Ca2+ activation in fast- but not slow-twitch fibres could account for the greater H(+)-induced depression of maximum force in fast-twitch fibres. In both fibre types, the decrease in the number of cross-bridge attachments at submaximal concentrations of Ca2+ may in part account for the loss in Ca2+ sensitivity of tension at low pH, due perhaps to a reduction in co-operative activation of the thin filament by bound cross-bridges.

Animals↗
PubMed1990

pH modulation of the kinetics of a Ca2(+)-sensitive cross-bridge state transition in mammalian single skeletal muscle fibres.

1. The rate constant of tension redevelopment (ktr) following a rapid release and subsequent re-extension of muscle length has been demonstrated to be Ca2+ sensitive and is thought to reflect the rate-limiting step in the cross-bridge cycle leading to the formation of the strongly bound, force-bearing state. The kinetics of this cross-bridge state transition were investigated at 15 degrees C over a wide range of Ca2+ concentrations while varying pH from 7.00 to 6.20 in rat slow-twitch soleus, rat fast-twitch superficial vastus lateralis (SVL) and rabbit fast-twitch psoas skinned single fibres. 2. At maximal levels of Ca2+ activation, ktr was unaffected by changes in pH from 7.00 to 6.20 while isometric tension was depressed to 0.60 +/- 0.02 P0 (mean +/- S.E.M.) at the low pH in fast-twitch fibres and to 0.78 +/- 0.01 P0 in slow-twitch fibres (P0 is the maximum isometric tension obtained at pH 7.00). 3. At reduced levels of Ca2+ activation, corresponding to pCa (-log [Ca2+]) greater than 5.0, ktr was markedly depressed in all fibre types when pH was lowered. The Ca2+ sensitivity of steady-state isometric tension was also reduced in all fibres at pH 6.20 compared to pH 7.00. 4. The results suggest that pH has a modulatory effect upon an apparent rate constant which is rate limiting in terms of the formation of the strongly bound, force-bearing cross-bridge state. This effect of altered pH may in part account for the reduction in the Ca2+ sensitivity of isometric force at low pH as well as the depression of the rate of rise of tension in living fibres during fatiguing stimulation.

Animals↗
PubMed1990

Differential effects of a luteinizing-hormone-releasing hormone (LHRH) antagonist analogue on lordosis behavior induced by LHRH and the LHRH fragment Ac-LHRH5-10.

Both the luteinizing-hormone-releasing hormone (LHRH) decapeptide and an LHRH fragment consisting of the last 6 amino acids of the decapeptide, Ac-LHRH, have been shown to enhance lordosis behavior in ovariectomized, estradiol-benzoate treated female rats. Although the behavioral efficacy of the 2 peptides is similar, several lines of research suggest that the fragment and the decapeptide may act via different mechanisms. The present study attempted to differentiate the behavioral action of the 2 peptides by administering a long-acting LHRH antagonist analogue prior to infusion of either Ac-LHRH or LHRH. Without antagonist administration, the decapeptide and the fragment were equally effective in elevating lordotic posturing 90 min after bilateral infusion through cannulae positioned in the ventromedial nucleus of the hypothalamus (VMH). Infusion of a potent LHRH antagonist analogue [Ac-dehydro, Pro, pCl, D-Phe, DTrp]-LHRH, into the VMH significantly reduced the lordosis-to-mount ratio in animals subsequently treated with the LHRH decapeptide, but had no significant effect on lordotic behavior when the animals were subsequently infused with the Ac-LHRH fragment. The results indicate that LHRH enhancement of mating behavior is a receptor-mediated event and suggest that the Ac-LHRH fragment enhances lordotic behavior via a mechanism that is distinct from that of the LHRH decapeptide.

Animals↗
PubMed1990

Role of the vomeronasal organ in the male-induced enhancement of sexual receptivity in female rats.

The role of the vomeronasal organ (VNO) in the male-induced enhancement of sexual receptivity in ovariectomized estrogen-primed rats was investigated. Removal of the VNO significantly reduced the enhancement of sexual receptivity following mating, as compared with the sham-operated controls. The sham-operated females exhibited a surge of luteinizing hormone (LH) following mating; however, LH release induced by pairing with males was less manifested in the VNO-removed females. This suggests that in female rats, VNO removal impairs the male-induced release of LH-releasing hormone (LHRH). Since LHRH enhances sexual receptivity in ovariectomized estrogen-primed rats, the present results suggest that the increase in sexual receptivity in female rats following mating probably results from a VNO-mediated LHRH release.

Animals↗
PubMed1989

Electrophysiology and pharmacology of neurons of the medial zona incerta: an in vitro slice study.

The electrical properties and chemical sensitivities of neurons located in the medial zona incerta (ZI), a region containing a clustering of dopaminergic cell bodies known as the A13 cell group, were studied in Sprague-Dawley female rats in the in vitro slice preparation. Extracellular single cell recordings were made from 473 neurons located in the medial ZI. The neurons generally displayed a slow and regular firing pattern with a mean firing rate of 4.7 impulses/s. Some neurons exhibited an orthodromic response to electrical stimulation of the ventromedial nucleus of the hypothalamus (VMH). The response consisted of a short-term, variable-latency increase in activity, indicating a predominantly excitatory input from the VMH to the medial ZI. The chemical sensitivity of medial ZI neurons was tested by micropressure application of various neurotransmitters and peptides. Dopamine and serotonin were found to inhibit the spontaneous firing in many of the neurons tested, whereas none of the peptides tested consistently produced a short-term change in firing rate. Over half (51%) of the cells that were orthodromically excited by VMH stimulation were also inhibited by the exogenous application of dopamine. Since many of the cells in the medial ZI are dopaminergic and are believed to be autoregulated, the present findings indicate that a portion of the VMH neurons that project to the medial ZI may be synapsing on dopaminergic neurons.

Action Potentials↗
PubMed1989

Re-evaluation of the effects of norepinephrine on the single-unit activity of paraventricular neurosecretory neurons.

Electrical stimulation of the A1 noradrenergic region elicited predominantly an excitatory orthodromic response from paraventricular neurosecretory neurons recorded in urethane-anesthetized male rats. In a majority of cases, locally applied norepinephrine (NE) as well as A1 region stimulation excited paraventricular neurosecretory neurons. However, in some neurons including a subpopulation of putative vasopressin neurons, iontophoresed NE was inhibitory. Both excitatory and inhibitory effects of NE were selectively blocked by the alpha-antagonist, phentolamine, but not by the beta-antagonist, timolol. In general, the results support the notion that the A1 noradrenergic input to paraventricular neurosecretory neurons is excitatory. Nevertheless, the results do not exclude the possibility that NE exerts a specific, alpha-receptor-mediated, inhibitory effect on a subpopulation of paraventricular neurons.

Action Potentials↗
PubMed1989

Inhibitory effect of norepinephrine on the single-unit activity of caudally projecting paraventricular neurons.

The role of norepinephrine (NE) in controlling the single-unit activity of paraventricular (PVN) neurons projecting to or passing through the caudal ventrolateral medulla (CVLM) was investigated in adult male rats anesthetized with urethane. Of 72 PVN neurons studied, 19 were antidromically activated by CVLM stimulation (Group I) and 48 were antidromically activated by posterior pituitary (PP) stimulation (Group II). The remaining 5 neurons were antidromically driven by both CVLM and PP stimulation (Group III). In 14 of the 19 Group I neurons and in all the 5 Group III neurons, iontophoretically applied NE was demonstrated to be inhibitory to the single-unit activity. No excitatory effect of NE was observed. In contrast, both excitatory and inhibitory actions of NE were observed in the Group II neurons. Of 37 Group II neurons tested, 28 were excited and 7 were inhibited by NE. The inhibitory effect of NE in Group I and Group III neurons was selectively blocked by the alpha antagonist, phentolamine, that was coiontophoresed with NE, but not by the beta antagonist, timolol (n = 9). The unit activity of Group I neurons that were inhibited by NE was not altered by an increase in arterial blood pressure (n = 3), whereas the unit activity of one NE-insensitive Group I neuron was decreased by an increase in blood pressure. Taken together, the results suggest that NE plays an alpha-adrenoreceptor-mediated inhibitory role in controlling the single-unit activity of caudally projecting PVN neurons. These neurons include a subpopulation of PVN neurons that project caudally as well as to the PP. The possible function associated with the NE-sensitive, caudally projecting PVN neurons may be other than the regulation of blood pressure.

Animals↗
PubMed1989

Variations in cross-bridge attachment rate and tension with phosphorylation of myosin in mammalian skinned skeletal muscle fibers. Implications for twitch potentiation in intact muscle.

The Ca2+ sensitivities of the rate constant of tension redevelopment (ktr; Brenner, B., and E. Eisenberg. 1986. Proceedings of the National Academy of Sciences. 83:3542-3546) and isometric force during steady-state activation were examined as functions of myosin light chain 2 (LC2) phosphorylation in skinned single fibers from rabbit and rat fast-twitch skeletal muscles. To measure ktr the fiber was activated with Ca2+ and steady isometric tension was allowed to develop; subsequently, the fiber was rapidly (less than 1 ms) released to a shorter length and then reextended by approximately 200 nm per half sarcomere. This maneuver resulted in the complete dissociation of cross-bridges from actin, so that the subsequent redevelopment of tension was related to the rate of cross-bridge reattachment. The time course of tension redevelopment, which was recorded under sarcomere length control, was best fit by a first-order exponential equation (i.e., tension = C(1 - e-kt) to obtain the value of ktr. In control fibers, ktr increased sigmoidally with increases in [Ca2+]; maximum values of ktr were obtained at pCa 4.5 and were significantly greater in rat superficial vastus lateralis fibers (26.1 +/- 1.2 s-1 at 15 degrees C) than in rabbit psoas fibers (18.7 +/- 1.0 s-1). Phosphorylation of LC2 was accomplished by repeated Ca2+ activations (pCa 4.5) of the fibers in solutions containing 6 microM calmodulin and 0.5 microM myosin light chain kinase, a protocol that resulted in an increase in LC2 phosphorylation from approximately 10% in the control fibers to greater than 80% after treatment. After phosphorylation, ktr was unchanged at maximum or very low levels of Ca2+ activation. However, at intermediate levels of Ca2+ activation, between pCa 5.5 and 6.2, there was a significant increase in ktr such that this portion of the ktr-pCa relationship was shifted to the left. The steady-state isometric tension-pCa relationship, which in control fibers was left shifted with respect to the ktr-pCa relationship, was further left-shifted after LC2 phosphorylation. Phosphorylation of LC2 had no effect upon steady-state tension during maximum Ca2+ activation. In fibers from which troponin C was partially extracted to disrupt molecular cooperativity within the thin filament (Moss et al. 1985. Journal of General Physiology. 86:585-600), the effect of LC2 phosphorylation to increase the Ca2+ sensitivity of steady-state isometric force was no longer evident, although the effect of phosphorylation to increase ktr was unaffected by this maneuver.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗