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Biomedical subjects

R L Moss

Publications and source records attributed to R L Moss.

At least 163 records · Page 9Linked to original sources
PubMed1988

Neuronal membrane sensitivity to a salmon calcitonin analogue with negligible ability to lower serum calcium.

The effects of [Gly8-des-Leu16-D-Arg24]-salmon calcitonin (CTA) on spontaneous extracellular activity and the passive membrane properties of rat forebrain neurons were studied in vivo and in vitro. This analogue had negligible ability to lower serum calcium relative to salmon calcitonin (SCT), however, the pattern of neuronal membrane sensitivity to CTA was similar to that produced by SCT and calcitonin generelated peptide. Depression of extracellularly recorded spontaneous action potential firing rate was the predominant response of neurons to microiontophoretic application of each peptide in vivo. Intracellular recordings from septal neurons suggest that the extracellularly observed inhibitory effects may be due to changes in membrane potential. We conclude that different structure-activity relationships may apply to the pharmacological effects of calcitonin in brain and its serum calcium-lowering action.

Action Potentials↗
PubMed1988

Facilitation of lordosis in female rats by CNS-site specific infusions of an LH-RH fragment, Ac-LH-RH-(5-10).

Structural alterations of the luteinizing hormone-releasing hormone (LH-RH) molecule have been performed to yield analogs which are more potent than, or which compete with, the parent hormone to increase the release of LH from the pituitary gland. The effects of these analogs on mating behavior, however, do not always parallel their effects on LH release. The present study tested the effectiveness of a pituitary-inactive fragment of LH-RH, namely Ac-LH-RH-(5-10), in potentiating mating behavior in the ovariectomized, estrogen-primed female rat. This fragment, when infused bilaterally into the medial preoptic area (POA), the ventromedial hypothalamus (VMH), or the midbrain central gray (MCG), significantly enhanced lordosis. Infusion of the fragment into the cerebral cortex was ineffective. Elevated lordotic responding was first apparent in the POA at 15 min postinfusion and was maintained for the duration of the testing session (180 min). Ac-LH-RH-(5-10) infused into the VMH or MCG enhanced lordotic behavior at 90 and 180 min postinfusion. The results indicate that only a portion of the LH-RH molecule may be required for behavioral activity and suggest that degradation of the LH-RH molecule is physiologically relevant.

Animals↗
PubMed1988

A1 noradrenergic action on medial preoptic-medial septal neurons: a neuropharmacological study.

In an attempt to determine whether the excitatory and inhibitory orthodromic responses of single medial preoptic-medial septal (MPO-S) neurons to discrete electrical stimulation of the A1 noradrenergic region were mediated specifically by norepinephrine (NE) and involved different types of adrenoreceptors, a series of electrophysiological and neuropharmacological experiments was conducted. Extracellular single unit recording and local drug application techniques were used in female rats under urethane anesthesia. Chemical lesion of the catecholaminergic nerve terminal plexus in the medial preoptic area with 6-hydroxydopamine abolished both excitatory and inhibitory orthodromic effects of A1 region stimulation on MPO-S neurons, suggesting the noradrenergic nature of the effects. This conclusion was corroborated by the observation that the orthodromic effects were mimicked by locally applied exogenous NE. The excitatory effects were reliably mimicked by a low concentration of NE (0.5 mM; in-barrel concentration) and methoxamine (1.0 mM, an alpha-1 agonist), but not by either low or high concentrations (1 and 100 mM) of clonidine (an alpha-2 agonist) and isoproterenol (a beta agonist). The inhibitory orthodromic effects of A1 region stimulation were reliably mimicked by a high concentration of NE (50 mM), clonidine (100 mM) and isoproterenol (100 mM), but not by a low concentration of NE (0.5 mM), methoxamine (1 mM), clonidine (1 mM) or isoproterenol (1 mM). A high concentration (100 mM) of methoxamine mimicked the inhibitory effects less than 40% of the time. The low concentration (0.5 mM) NE-induced excitation that matched the excitatory orthodromic effect of A1 region stimulation was blocked by phentolamine (100 mM), an alpha blocker, but not by timolol (100 mM), a beta blocker. On the other hand, the high concentration (50 mM) NE-induced inhibition that matched the inhibitory orthodromic effect of A1 region stimulation was blocked by timolol, but not by phentolamine. Taken together, the present results are consistent with the hypotheses that the ascending noradrenergic projections from the A1 region affect the excitability of MPO-S neurons directly through NE and that the excitatory and inhibitory orthodromic effects involve different types of adrenoreceptors, i.e., alpha-1 and beta receptors, respectively.

Action Potentials↗
PubMed1988

Myosin heavy chain composition of single cells from avian slow skeletal muscle is strongly correlated with velocity of shortening during development.

We have determined the myosin heavy chain (MHC) composition (using a sensitive sodium dodecyl sulfate-polyacrylamide gel electrophoresis system) and the maximal velocity of shortening (Vmax) of single cells from neonatal and adult chicken anterior latissimus dorsi (ALD) muscles. In addition, the MHC, myosin light chain, and regulatory protein (i.e., troponin and tropomyosin subunits) compositions of bundles of ALD fibers were determined at late embryonic, neonatal, and adult ages. At young ages, there are two MHCs in ALD muscle, SM1 and SM2, with SM1 decreasing in relative amount with increasing age, as shown previously by others. The mean Vmax of single fibers also decreases from neonatal to adult ages. A strong quantitative correlation is demonstrated between the specific MHC composition and Vmax among individual cells of the ALD muscle at several ages. Since virtually no changes occur in the regulatory protein and myosin light chain compositions of the ALD muscle between late embryonic and adult ages, it appears that the MHC composition of an individual cell in this muscle is the primary determinant of the maximal shortening velocity. These results are the first to illustrate the functional significance of the developmental transition in myosin heavy chain composition of an avian slow skeletal muscle, consistent with our previous findings on mammalian muscle.

Animals↗
PubMed1988

Immunocytochemical localization of hypothalamic luteinizing hormone-releasing hormone in male ferrets.

LHRH-containing neurons within the hypothalamus were immunocytochemically identified in adult male ferrets that were either gonadally intact, castrated, or castrated and treated with testosterone. The distribution of LHRH-immunopositive neuron cell bodies was similar in the three treatment groups. The majority of these cells was located mediobasally in the retrochiasmatic area, including some within the ventrolateral aspects of the arcuate nucleus. These soma were associated with a dense basal LHRH fiber plexus which extended to the median eminence. A smaller number of cell bodies was found slightly more dorsal and lateral to the major concentration at the base and midline. Isolated LHRH perikarya were occasionally observed in dorsal areas of the hypothalamus. There were no differences in the mean total number of hypothalamic LHRH cell bodies identified in the three treatment groups. These results indicate that the documented negative feedback effects of testosterone on LH secretion in male ferrets are not the result of an alteration in the absolute number of neurons capable of synthesizing LHRH.

Animals↗
PubMed1988

Depression of Ca2+ insensitive tension due to reduced pH in partially troponin-extracted skinned skeletal muscle fibers.

Previous studies on skinned muscle fibers have demonstrated a direct effect of elevated levels of H+ ion to depress force production; however, the molecular basis for this effect is presently unknown. Here, whole troponin complexes were removed from skinned single fiber preparations of rat slow-twitch and fast-twitch muscles, and the effect of H+ ions on the resultant Ca2+-insensitive force was examined. The effect of H+ ions to depress force was found to be virtually identical in untreated control fibers activated in the presence of Ca2+ and in fibers activated in the absence of Ca2+ by troponin removal. Thus, the effect of H+ ions to depress force occurs at a step in activation beyond the disinhibition of the thin filament by Ca2+, probably involving reductions in the number of attached cross-bridges or in the force per attachment.

Animals↗
PubMed1988

Cutaneous Crohn's disease and progressive vitiligo.

A patient with Crohn's colitis rapidly developed violaceous papules and plaques on the thigh, breast, and back during an exacerbation of colitis. Biopsy specimens of lesional bowel and skin showed noncaseating granulomatous inflammation consistent with Crohn's disease. The rare occurrence of granulomatous skin lesions widely separated from the perirectal area, previously reported as metastatic Crohn's disease, is reviewed, and the additional finding of concomitant vitiligo with a possible linked pathogenesis is briefly discussed.

Adult↗
PubMed1988

Thin filament regulation of shortening velocity in rat skinned skeletal muscle: effects of osmotic compression.

1. Maximum shortening velocity (Vmax) was examined in skinned single fibres from rat slow-twitch soleus muscles at various degrees of Ca2+ activation of the thin filament, in the presence and absence of osmotic compression induced by 5% dextran. 2. At maximal levels of Ca2+ activation, Vmax remained constant as the extent of shortening was varied, with values averaging 1.43 +/- 0.05 muscle lengths/s (mean + S.E.M., n = 13). When thin filament activation was reduced by lowering the concentration of Ca2+, unloaded shortening consisted of an initial high-velocity phase for extents of shortening in the range 20-80 nm/half-sarcomere, and a subsequent low-velocity phase for greater extents of shortening. 3. In the absence of dextran, Vmax in the high-velocity phase of shortening was relatively invariant over a wide range of activation; however, at very low levels of activation, yielding tensions less than 5% of the peak value. Vmax declined precipitously. In contrast, fibres compressed radially with dextran to diameters comparable to those of intact fibres demonstrated a marked decrease in Vmax in the high-velocity phase when thin filament activation was varied over a wide range. These findings are consistent with the idea that cross-bridges in the expanded filament lattice of skinned fibres do not bear as great an axial compressive force as in intact fibres (Goldman & Simmons, 1986; Goldman, 1987) but instead buckle as the fibre shortens. 4. The value of Vmax in the low-velocity phase of shortening decreased as thin filament activation was reduced in both control and osmotically compressed fibres. The low-velocity phase, which occurred only at reduced levels of thin filament activation, may be a manifestation of a population of slowly dissociating crossbridges which with shortening become negatively strained and oppose contraction.

Animals↗
PubMed1988

Variations in contractile properties of rabbit single muscle fibres in relation to troponin T isoforms and myosin light chains.

1. The maximal velocity of shortening (Vmax), tension-pCa relationships and the contractile and regulatory protein composition were determined in single, chemically skinned fibres from adult rabbit plantaris muscles. 2. Three groups of fibres were identified based on their protein compositions. One group had exclusively the slow-type myosin heavy chain (MHC) and myosin light chains (LC) and had low velocities. Another group of fibres had mixtures of fast-type and slow-type MHCs and LCs and had intermediate shortening velocities. The third group of fibres had fast-type myosin heavy and light chains and high velocities. 3. The low-velocity fibres had a mean velocity (+/- S.E.M.) of 0.86 +/- 0.03 muscle lengths/s (ML/s) at 15 degrees C. The remaining fibres formed a continuum with respect to Vmax from 1.37 to 3.94 ML/s. These results indicate that a much greater diversity exists among single fibres from adult mammalian skeletal muscle than previously recognized. The intermediate- and high-velocity fibres formed a continuum (from slow to fast) with respect to the amount of myosin light chain 3 (LC3). That is, Vmax increased with the relative LC3 content in single fibres in the intermediate- and high-velocity groups in a quantitative, statistically significant manner. 4. Three isoforms of fast-type troponin T were identified among the intermediate- and high-velocity fibres. These fibres also contained fast-type troponin C and troponin I. As was the case with the relative LC3 content, these fibres also formed a continuum with respect to the relative proportions of the three isoforms of fast-type troponin T. It appears that different isoforms of troponin T are responsible for a slightly higher Ca2+ sensitivity of tension development in the high-velocity fibres compared to the intermediate fibres. The continuum in troponin T isoform composition paralleled an increase in Vmax among these fibres. 5. The low-velocity fibres had the highest Ca2+ sensitivity of the three groups and had exclusively the slow-type isoforms of the regulatory proteins in the troponin complex. 6. The co-ordinated variations in troponin T and LC3 compositions among the intermediate- and high-velocity fibres are discussed as a possible means for the further differentiation of the contractile properties of the fibres in these two groups, beyond that provided by myosin heavy chain isoforms alone.

Animals↗
PubMed1988

Functional significance of myosin transitions in single fibers of developing soleus muscle.

The maximal velocity of shortening and myosin heavy chain (MHC) composition of single, chemically skinned fibers from neonatal and adult rat soleus muscles were examined to determine the relationship between these parameters during slow muscle development in the rat. In addition, the MHC composition of bundles of fibers from soleus muscles at the same ages was studied. The MHC compositions were examined using sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The results from the bundles of fibers indicate that from 3 days to 5 mo postnatal, the rat soleus contains predominantly MHCs that migrate in the vicinity of the MHC from adult slow muscle. From 14 days to 2 mo postnatal, there are also significant amounts of additional MHCs that comigrate on SDS gels with those characteristic of adult rat fast muscle. All the fibers studied at 3 and 7 days postnatal and at 5 mo and the majority of fibers from 14 days to 2 mo postnatal had relatively low shortening velocities. A few fibers from the latter group had significantly higher velocities. The faster fibers at each age had greater amounts of the MHCs that comigrate with the adult fast-type MHC on SDS gels. Thus the velocity of shortening of single fibers from the rat soleus muscle appears to be related to MHC composition during postnatal development.

Animals↗
PubMed1987

Elevated fetal hemoglobin levels in sudden infant death syndrome.

The cause of sudden infant death syndrome (SIDS) is unknown, although deficits in cardiopulmonary function and central respiratory control have been suggested as possible mechanisms of the disorder. In this study, we tested the hypothesis that SIDS is associated with a delay in the maturation of hematopoiesis. Prolonged elevation in the levels of fetal hemoglobin (hemoglobin F) in infants with SIDS could denote a compromised delivery of oxygen to sensitive tissue sites. Normally, hemoglobin F (alpha 2 gamma 2) is largely replaced by adult hemoglobin, hemoglobin A (alpha 2 beta 2), during the first six months after birth. Using an isoelectric-focusing procedure for measuring stable hemoglobin subunits, we quantitated the levels of hemoglobin F in blood samples from 59 patients with SIDS and 40 controls (32 living and 8 dead) matched for postconceptional age. The level of hemoglobin F in the population with SIDS was significantly higher than that in the controls in the age range tested (39 to 75 weeks); the mean (+/- SEM) proportion of hemoglobin F was 63.2 +/- 3.6 percent in the group with SIDS, as compared with 48.1 +/- 5.0 percent in the controls (P less than 0.025). The difference in hemoglobin F levels was most pronounced 50 weeks after conception: the proportion of hemoglobin F in the 37 patients with SIDS with a postconceptional age of more than 50 weeks was 47.4 +/- 3.6 percent, as compared with 18.8 +/- 3.1 percent in the 19 controls of that age (P less than 0.0005). We conclude that hemoglobin F is a useful postmortem marker for the population with SIDS that we studied and that it may have value as a prospective marker for some infants at risk for SIDS.

Age Factors↗
PubMed1987

Effects of a behaviorally active LHRH fragment and septal area stimulation on the activity of mediobasal hypothalamic neurons.

The effect of Ac-LHRH, an LHRH fragment capable of facilitating lordosis, and LHRH on the firing rate of mediobasal hypothalamic neurons receiving input from the septal area, (a site containing the majority of LHRH perikarya) was studied via conventional extracellular recording techniques. A multibarrelled glass electrode assembly was lowered through the dorsomedial and ventromedial hypothalamus to detect single units responsive to septal area stimulation, and to iontophoretically apply Ac-LHRH and LHRH. Ovariectomized rats were primed with estradiol benzoate (EB; n = 21) or left untreated (n = 34) to determine if the neuronal responsiveness to septal area stimulation and/or to the two peptides was subject to estrogenic modulation. Of the total number of 228 neurons recorded in the study, 51 units (22.4%) were orthodromically responsive to septal area stimulation. The orthodromic responses in EB-primed animals (n = 20) were characterized by a short-latency, short-duration increase in membrane excitability. When spontaneous activity was sufficiently high, the excitatory response was followed by, or superimposed upon, an inhibitory response of longer duration. Similar orthodromic excitatory and inhibitory response characteristics were observed in 21 of the 31 neurons recorded in nonprimed animals. In the remaining ten neurons, however, the excitatory component was absent. Iontophoretic application of both Ac-LHRH and LHRH was found to produce predominantly an inhibitory effect on cell firing. Most neurons responded to the two peptides in a similar manner (i.e., inhibited by both peptides, excited by both peptides, or not effected by either peptide).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1987

Shortening velocity in skinned single muscle fibers. Influence of filament lattice spacing.

In this study maximum shortening velocity (Vmax) and isometric tension (P0) in skinned single fibers from rat slow soleus (SOL) and fast superficial vastus lateralis (SVL) muscles were examined after varying degrees of filament lattice compression with dextran. In both fiber types Vmax was greatest in the absence of dextran and decreased as the concentration of dextran was increased between 2.5 and 10 g/100 ml. At 10% dextran, which compressed fiber width by 31-38%, Vmax relative to the initial 0% dextran value was 0.28 +/- 0.03 (mean +/- SE) and 0.26 +/- 0.02 in SVL and SOL fibers, respectively. The effect of compression to depress Vmax was reversed completely by returning the fiber to 0% dextran. The force-generating capability of skinned fibers was not as sensitive to variations in cell width. In both the SOL and SVL fibers P0 increased by 3-7% when the concentration of dextran was increased from 0 to 5%. Further compression of lattice volume with 10% dextran resulted in a 8-13% decline in P0 relative to the initial value. While the precise mechanism by which filament lattice spacing modulates contractile function is not known, our results suggest that the major effect is upon the rate constant for cross-bridge detachment.

Animals↗
PubMed1987

Factors influencing the ascending limb of the sarcomere length-tension relationship in rabbit skinned muscle fibres.

1. The length dependence of Ca2+-activated tension within the ascending limb of the length-tension relationship, corresponding to sarcomere lengths below about 2.25 micron, was investigated in skinned fibres from rabbit psoas muscle. At high [Ca2+] a shallow phase and then a steep phase of tension decline were observed as sarcomere length was reduced, while at low [Ca2+] tension decreased monotonically with decreases in sarcomere length. The sarcomere length at which the ascending limb intersected zero tension was greater for lower concentrations of Ca2+. 2. The length tension relationship from maximally activated fibres changed when filament lattice spacing was reduced by osmotic compression. Relationships obtained in the presence of 5% (w/v) dextran T500 more distinctly demonstrated both the shallow and steep portions of the ascending limb than did relationships from untreated fibres. 3. As striation spacing was decreased a progressive decline in the Ca2+ sensitivity of tension development was observed. Tension-pCa relationships from both control and dextran-treated fibres underwent a rightward shift (i.e. to a higher [Ca2+]) by 0.23 pCa units as sarcomere length was reduced between 2.46 and 1.54 microns. 4. Fibre stiffness was studied by applying a 3.3 kHz sinusoidal length change at one end of the fibre and measuring the resultant tension change. At submaximal activation (pCa 5.8), stiffness increased relative to tension as sarcomere length was decreased below approximately 2.4 microns, suggesting that there is an activation-related internal load at low [Ca2+]. At maximal activation, a significant increase in this ratio occurred only at sarcomere lengths less than approximately 1.8 microns, and presumably involved collision of the thick filaments with the Z-lines. 5. Length-dependent changes in the Ca2+ sensitivity of tension development do not appear to be the result of shortening-induced dissociation of Ca2+ from troponin-C, the Ca2+ binding subunit of troponin. Fibres activated in the absence of Ca2+, by the partial removal of whole troponin complexes, produced length-tension relationships similar to those observed in the same fibres before troponin removal at a submaximal [Ca2+] yielding similar active tensions.

Animals↗
PubMed1987

Greater hydrogen ion-induced depression of tension and velocity in skinned single fibres of rat fast than slow muscles.

1. The effects of variations in pH between 7.00 and 6.20 on Ca2+ -activated tension development and maximum velocity of shortening (Vmax) were examined in skinned single skeletal fibres from rat slow-twitch soleus and fast-twitch superficial (s.v.l.) and deep (d.v.l.) regions of the vastus lateralis muscle. 2. At pH 6.50, Vmax was depressed to a similar degree in each of the soleus, d.v.l., and s.v.l. fibres. Lowering pH to 6.20 resulted in a further decline in Vmax in all fibres; however, differences between the slow fibres, identified by SDS-polyacrylamide gel electrophoresis, and fast fibres were apparent, with soleus retaining a significantly greater proportion of its control Vmax (0.83 +/- 0.03 in soleus vs. 0.69 +/- 0.03 in s.v.l.; mean +/- S.E.M.). 3. Maximum force production decreased significantly as pH was reduced. Peak force at pH 6.50, relative to that at pH 7.00, was significantly greater in soleus (0.80 +/- 0.01) than in the s.v.l. (0.75 +/- 0.01) fibres. At pH 6.20 these differences between slow and fast fibres were still greater, in that soleus fibres generated significantly greater relative forces (0.73 +/- 0.01) than did d.v.l. (0.67 +/- 0.02) or s.v.l. (0.63 +/- 0.02) fibres. 4. As pH was lowered the tension-pCa relationship shifted to the right (i.e. to higher [Ca2+]), indicating a reduction in the Ca2+ sensitivity of tension development. The [Ca2+] necessary to achieve half-maximal tension in both the slow- and fast-twitch fibres increased approximately 5-fold when pH was lowered from 7.00 to 6.20. Furthermore, in the case of the soleus, the Ca2+ threshold for tension development was 45 times greater at pH 6.20 than at pH 7.00, while in the fast-twitch fibres, this increase was 4-fold. 5. Increased [H+] differentially affected the steepness of the tension-pCa relationship between slow and fast fibres. As pH was lowered, the steepness of the lower portion of the tension-pCa curve increased in the soleus and decreased in d.v.l. and s.v.l., suggesting that apparent positive co-operativity of tension development had increased in soleus and decreased in d.v.l. and s.v.l. fibres. 6. These results (1) demonstrate an increased resistance to H+ ion-mediated contractile dysfunction in slow- compared to fast-twitch single fibres, and (2) support the hypothesis that muscular fatigue resulting from short-term, intense muscular contraction may in part be related to elevated H+ ion concentration.

Animals↗
PubMed1987

Mechanical properties of skinned single fibers of identified types from rat diaphragm.

Maximum isometric tension (Po), maximum velocity of shortening (Vmax), and tension-pCa (i.e., -log[Ca2+]) relationships were determined in single skinned fibers from rat diaphragm. Histochemistry (myosin-ATPase) and sodium dodecyl sulfate (SDS) gel electrophoresis were performed on these same fibers to determine fiber type and protein composition. Physiologically fast fibers were found to have larger cross-sectional areas (CSA) and produced more tension per CSA and were less sensitive to [Ca2+] than physiologically slow fibers. Fast fibers were typed histochemically as type II and contained myosin heavy chains (MHC) and light chains (LC) of the fast type, whereas the slow fibers contained slow MHC and LC. There were also corresponding differences in the regulatory protein composition of these two fiber types. The histochemical sections confirmed a significant fiber size difference between the type IIa and IIb fibers. When fiber size was used to separate the fast fibers into two groups, type IIb fibers were found to have significantly greater Vmax and tension per CSA than the type IIa fibers. Although there were no noticeable differences in MHC composition between the type IIa and IIb fibers, there were some differences in the myosin LC and regulatory protein content.

Animals↗
PubMed1987

Myosin subunits and contractile properties of single fibers from hypokinetic rat muscles.

The effects of prolonged hypokinesia on the contractile properties and myosin isozymes of single fibers from the synergistic fast-twitch plantaris (PL) and slow-twitch soleus (SOL) skeletal muscles of adult rats were studied after 28 days of hindlimb suspension. There was a 31% increase in the mean maximal velocity of unloaded shortening (Vmax) among fibers from SOL with no change in the mean Vmax of fibers from PL after suspension. The myosin heavy and light chain (MHC and MLC) composition of bundles and the MHC composition of single fibers from control and suspended muscles were examined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. There was a marked increase in the relative amount of fast-type MHC's in hypokinetic SOL and a smaller increase in the amount of fast-type MHC's in the PL. Relatively minor changes occurred in the MLC's during hypokinesia. As Vmax increased among individual fibers from control and suspended muscles, the relative amount of fast-type MHC's increased. The results demonstrate that the myosin isozyme composition of skeletal muscle, especially the heavy chains, is altered during hypokinesia, and this finding provides an explanation for changes in Vmax of rat single muscle fibers under the same conditions.

Adenosine Triphosphatases↗