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Biomedical subjects

R L Ruff

Publications and source records attributed to R L Ruff.

At least 37 records · Page 2Linked to original sources

Serological survey for diseases in free-ranging coyotes (Canis latrans) in Yellowstone National Park, Wyoming.

From October 1989 to June 1993, we captured and sampled 110 coyotes (Canis latrans) for various diseases in Yellowstone National Park, Wyoming (USA). Prevalence of antibodies against canine parvovirus (CPV) was 100% for adults (> 24 months old), 100% for yearlings (12 to 24 months old), and 100% for old pups (4 to 12 months old); 0% of the young pups (< 3 months old) had antibodies against CPV. Presence of antibodies against canine distemper virus (CDV) was associated with the age of the coyote, with 88%, 54%, 23%, and 0% prevalence among adults, yearlings, old pups, and young pups, respectively. Prevalence of CDV antibodies declined over time from 100% in 1989 to 33% in 1992. The prevalence of canine infectious hepatitis (ICH) virus antibodies was 97%, 82%, 54%, and 33%, for adults, yearlings, old pups, and young pups, respectively. The percentage of coyotes with ICH virus antibodies also declined over time from a high of 100% in 1989 to 31% in 1992, and 42% in 1993. Prevalence of antibodies against Yersinia pestis was 86%, 33%, 80%, and 7%, for adults, yearlings, old pups, and young pups, respectively, and changed over time from 57% in 1991 to 0% in 1993. The prevalence of antibodies against Francisella tularensis was 21%, 17%, 10%, and 20%, for adults, yearlings, old pups, and young pups, respectively. No coyotes had serologic evidence of exposure to brucellosis, either Brucella abortus or Brucella canis. No coyotes were seropositive to Leptospira interrogans (serovars canicola, hardjo, and icterohemorrhagiae). Prevalence of antibodies against L. interrogans serovar pomona was 7%, 0%, 0%, and 9%, for adults, yearlings, old pups, and young pups, respectively. Antibodies against L. interrogans serovar grippotyphosa were present in 17% of adults and 0% of yearlings, old pups, and young pups. Many infectious canine pathogens (CPV, CDV, ICH virus) are prevalent in coyotes in Yellowstone National Park, with CPV influencing coyote pup survival during the first 3 months of life; eight of 21 transmitted pups died of CPV infection in 1992. The potential impact of these canine pathogens on wolves (C. lupus) reintroduced to Yellowstone National Park remains to be documented.

Adenoviruses, Canine↗

Effects of length changes on Na+ current amplitude and excitability near and far from the end-plate.

Na+ current (INa), membrane capacitance (Cm), action potential (AP) properties, and cable properties were studied on the end-plate (E), the end-plate border (EB), and extrajunctional (EJ) membrane of rat fast twitch muscle fibers. INa normalized to Cm, which is proportional to the density of Na+ channels, was the same on the E and the EB and smallest on EJ membrane. The AP threshold was lower and rate of rise of the AP was larger at the EB compared with EJ membrane. On the E and the EB, Cm and INa did not change in response to changes in fiber length. On EJ membrane, INa, Cm, and membrane cable properties changed in a manner consistent with folding and unfolding of the sarcolemma during length changes. The stiffness of the E membrane may add mechanical stability of the neuromuscular junction so that the electrical properties of the end-plate do not change with fiber length. The higher density of Na+ channels near the end-plate increases the safety factor for neuromuscular transmission by lowering the AP threshold.

Action Potentials↗

Sodium channel slow inactivation and the distribution of sodium channels on skeletal muscle fibres enable the performance properties of different skeletal muscle fibre types.

Na+ currents (INa) and membrane capacitance were studied with the loose patch voltage clamp technique and action potential properties were studied with a two-electrode voltage clamp on the end-plate, at the end-plate border and on extrajunctional membrane of skeletal muscle fibres. Slow inactivation regulates the available INa and is operative at the resting potential of both rat and human fibres. At the resting potential, slow inactivation causes a greater reduction in INa in fast-than in slow-twitch fibres. The relative resistance of slow-twitch fibres to slow inactivation may enable slow-twitch fibres to remain tonically active. Na+ channel inactivation may provide a peripheral mechanism that limits the duration that fast-twitch fibres can fire at high rates to prevent injury associated with prolonged high-frequency contraction. Consequently, slow inactivation may enable fast-twitch fibres to operate phasically at high rates or slow-twitch fibres to fire continuously at lower rates. For both fast- and slow-twitch fibres. INa normalized to membrane area was greatest on the end-plate, intermediate on the end-plate border and smallest on extrajunctional membrane. When normalized to membrane capacitance. INa was the same on the end-plate and the end-plate border and smallest on extrajunctional membrane. For a given membrane region, INa was larger on fast- than on slow-twitch fibres. The higher density of Na+ channels near the end-plate increased the safety factor for neuromuscular transmission by lowering the action potential threshold and increasing the action potential rate of rise at the end-plate.

Action Potentials↗

Single-channel basis of slow inactivation of Na+ channels in rat skeletal muscle.

This study examined the single-channel basis of slow inactivation of Na+ currents (INa) in rat fast-twitch skeletal muscle fibers. A loose patch voltage clamp monitored changes in the maximum inward INa as the holding potential of the membrane patch changed. On a neighboring region of extrajunctional membrane of the same fiber, a gigaohm seal patch voltage clamp recorded single-channel INa. The maximum number of simultaneously open Na+ channels among a group of current traces indicated the maximum number of excitable channels. The holding potentials of the two voltage clamps were the same. Slow inactivation did not affect the open time or conductance of single Na+ channels. The number of excitable Na+ channels reversibly decreased during development of slow inactivation of INa and increased during recovery from slow inactivation of INa. Different stimulation protocols examined whether Na+ channels had to be in the closed, open, or fast-inactivated states to enter the slow-inactivated state. Na+ channels appear to be able to enter the slow-inactivated state from the closed, open, or fast-inactivated state.

Animals↗

Elevated intracellular Ca2+ and myofibrillar Ca2+ sensitivity cause iodoacetate-induced muscle contractures.

Ischemic stimulation of iodoacetic acid (IAA)-treated rat extensor digitorum longus (EDL) muscles produced contractures. Similar ischemic stimulation of control EDL muscles did not result in contracture. At the onset of contracture, ATP concentration was not reduced, phosphocreatine concentration was reduced > 75%, ADP concentration was increased 9-fold, Ca2+ concentration ([Ca2+]) was increased approximately 11-fold, and inorganic phosphate concentration increased less in IAA-treated muscles than in stimulated control muscles. To test whether contracture resulted from elevated [Ca2+] and/or increased Ca2+ sensitivity of the contractile proteins, this laboratory made skinned fiber-activating solutions that simulated four different conditions: unstimulated IAA-treated and control muscles, IAA-treated muscles at contracture, and ischemically simulated control muscles. Skinned EDL fibers had lower single-fiber tensions and reduced Ca2+ sensitivities in activating solutions that mimicked the conditions in stimulated control muscles compared with activating solutions that simulated the conditions in unstimulated muscles. In contrast, the maximum tension was maintained and Ca2+ sensitivity was increased in activating solutions that simulated contracture. Tension at contracture resulted from increased intracellular [Ca2+] and increased myofibrillar Ca2+ sensitivity compared with the Ca2+ sensitivity of stimulated control fibers.

Animals↗

Iodoacetate-induced skeletal muscle contracture: changes in ADP, calcium, phosphate, and pH.

The effects of iodoacetic acid (IAA) and ischemic contraction were studied in rat extensor digitorum longus muscles. Ischemic stimulation of IAA-treated muscles produced contracture. We measured total muscle water content, distribution of water between intracellular and extracellular spaces, creatine concentration ([Cr]), creatine phosphate concentration ([PCr]), [ATP], [Pi], intracellular pH, and intracellular Ca2+ concentration ([Ca2+]i) at the onset of contracture. [ADP] was calculated from the equilibrium of the creatine kinase reaction using the measured values of [ATP], [PCr], [Cr], and pH. At the onset of contracture there was a 75% reduction of [PCr], a 12-fold increase in [ADP], and an 11-fold increase in [Ca2+]i compared with unstimulated IAA-treated muscles. [ATP] was not depleted at contracture compared with unstimulated IAA-treated muscles, and [Pi] increased less in muscles at contracture compared with stimulated control muscles. The persistent tension in contractures probably resulted from increased [Ca2+]i combined with increased myofibrillar Ca2+ sensitivity due to elevated [ADP] and relatively reduced intracellular acidification and [Pi].

Adenosine Diphosphate↗

The gamma-subunit of the acetylcholine receptor is not expressed in the levator palpebrae superioris.

In extraocular muscle (EOM), expression of the gamma-subunit, which is associated with the fetal-type acetylcholine receptor (AChR), may offer a differential target for immune-mediated damage and could explain the preponderance of ocular manifestations caused by myasthenia gravis (MG). Using Poly(A)+ RNA hybridization, we investigated expression of the gamma-subunit in bovine levator palpebrae superioris (LP), a muscle also differentially involved by MG. There were no transcripts of the gamma-subunit of the AChR, but the epsilon-subunit, associated with the adult-type AChR, was present. The results indicate that the susceptibility of LP to MG is not mediated by gamma-subunit expression and suggest that multiterminal fibers in EOM may be the site of gamma-subunit expression.

Animals↗

A four-drug pain regimen for head and neck cancers.

Twenty patients with end-stage head and neck cancer, unresponsive to either acetaminophen with codeine or oxycodone hydrochloride, were placed on a four-drug analgesic regimen consisting of methadone hydrochloride, Trilisate or acetaminophen, a tricyclic antidepressant, and, in most cases, hydroxyzine. All drugs could be delivered through a feeding tube, making this regimen appropriate for dysphagic patients. The efficacy of this nonparenteral regimen was assessed by structured pretreatment and posttreatment interviews that addressed pain intensity, activity, and sleep levels. All of the patients showed improvement in their pain levels and 16 of the 20 had a > or = 50% improvement in all of their pain ratings (P < .01) that persisted until death (2 to 10 months later). Excellent results and ease of administration make this regimen a good choice for analgesia in terminal patients.

Acetaminophen↗

Myf-4 does not mediate AChR receptor subunit mRNA expression in thymic tissues.

We investigated whether a MyoD gene family member plays a role in the expression of AChR or AChR-like proteins in human thymus. We amplified from thymic tissue, mRNA of subunits of the fetal- and adult-type AChR, and Myf-4, a gene product that appears to regulate AChR expression. RNA extracted from paraffin-embedded thymic tissue of five myasthenics and five nonmyasthenics was subjected to reverse transcription followed by polymerase chain reaction using primers specific for these mRNAs. Thymic RNA from eight of ten patients contained transcripts of the alpha- and epsilon-subunits (specific for the adult-type AChR). Presence of these transcripts did not correlate with thymic pathology or clinical presentation. No gamma-subunit (specific for the fetal-type AChR) or Myf-4 transcripts were found. Our results indicate that mRNA for the adult-type AChR is expressed in thymic tissue and is expressed by mechanisms not involving Myf-4. Thymic AChR subunits may be the primary epitope that initiates the immune response in MG against the adult-type AChR.

Adult↗

Na+ currents near and away from endplates on human fast and slow twitch muscle fibers.

Fast and slow twitch muscle fibers have distinct contractile properties. Here we determined that membrane excitability also varies with fiber type. Na+ currents (INa) were studied with the loose-patch voltage clamp technique on 29 histochemically classified human intercostal skeletal muscle fibers at the endplate border and > 200 microns from the endplate (extrajunctional). Fast and slow twitch fibers showed slow inactivation of endplate border and extrajunctional INa and had increased INa at the endplate border compared to extrajunctional membrane. The voltage dependencies of INa were similar on the endplate border and extrajunctional membrane, which suggests that both regions have physiologically similar channels. Fast twitch fibers had larger INa on the endplate border and extrajunctional membrane and manifest fast and slow inactivation of INa at more negative potentials than slow twitch fibers. For normal muscle, the differences between INa on fast and slow twitch fibers might: (1) enable fast twitch fibers to operate at high firing frequencies for brief periods; and (2) enable slow twitch fibers to operate at low firing frequencies for prolonged times. Disorders of skeletal membrane excitability, such as the periodic paralyses and myotonias, may impact fast and slow twitch fibers differently due to the distinctive Na+ channel properties of each fiber type.

Aged↗

Acetylcholine receptor subunit gene expression in thymic tissue.

It is controversial whether acetylcholine receptors (AChR) or AChR-like proteins exist in human thymus. To evaluate this question we isolated RNA from paraffin-embedded thymic tissue of 5 myasthenics and 5 nonmyasthenics. RNA was subjected to reverse transcription followed by polymerase chain reaction (RT-PCR) using primers specific for beta-actin, subunits of the fetal- and adult-type AChR, and Myf-4, a gene product which regulates AChR expression in muscle. beta-Actin transcripts were identified in specimens from 8 of 10 patients. In these 8 patients alpha- and epsilon-subunit transcripts were identified. Presence of these transcripts did not correlate with thymic pathology or clinical presentation. No gamma-subunit (specific for the fetal-type AChR) or Myf-4 transcripts were found. Our results indicate that mRNA for subunits of the adult-type AChR are expressed in thymic tissue by mechanisms not involving Myf-4. AChR subunits in pathological thymus may provide a target for immune attack in MG. However, as AChR subunits were found in thymus tissue from myasthenics and nonmyasthenics, the presence of AChR subunits in thymus alone is not sufficient to produce myasthenia gravis.

Actins↗

Spinal cord compression secondary to prostate carcinoma: treatment and prognosis.

Of 35 patients with prostate carcinoma and suspected spinal cord compression 26 (74%) had myelograms and/or magnetic resonance imaging studies demonstrating epidural spinal cord compression. In 5 of 26 patients (19%) spinal cord compression was the first indication of prostate cancer. All patients were initially treated with radiation, steroids and androgen deprivation therapy. Three patients underwent laminectomy. Of 12 patients (100%) ambulatory at presentation 12 remained ambulatory. Of 12 patients (83%) who were paraparetic at presentation 10 were ambulatory after treatment. However, 2 of these patients subsequently had recurrent compression and became paraplegic. Overall, 7 of 26 patients (27%) had recurrent compression. Of 5 patients who either presented with paraplegia or in whom paraplegia developed secondary to recurrent spinal cord compression 4 remained paraplegic despite treatment. The average survival of these 5 patients after treatment was 3.9 months versus 18 months for the group as a whole. In ambulatory or paraparetic patients radiation, androgen deprivation therapy and steroids are effective palliative therapy. However, patients who present with paraplegia or in whom paraplegia developed secondary to recurrent compression are often not palliated by this combination therapy. Prophylactic radiation of vertebral metastases discovered concurrently with compressive metastases may be valuable in preventing paraplegia.

Aged↗

Comparison of Na+ currents from type IIa and IIb human intercostal muscle fibers.

The voltage dependence and amplitude of Na+ currents (INa) were studied with the loose-patch voltage-clamp technique on 19 fast-twitch human intercostal skeletal muscle fibers at the endplate border and > 200 microns from the endplate (extrajunctional). The fibers were histochemically classified as fast-twitch oxidative-glycolytic (type IIa, n = 9) or fast-twitch glycolytic (type IIb, n = 10). The voltage dependence of activation and fast and slow inactivation of INa were similar for membrane patches recorded on the endplate border and on extrajunctional membrane for both fiber types. INa was about fivefold larger on the endplate border compared with extrajunctional membrane for both fiber types. Type IIb fibers had larger values of INa and manifest fast inactivation of INa at more negative potentials than type IIa fibers. The difference between type IIa and IIb fibers may enable IIb fibers to operate at higher firing frequencies for brief periods.

Aged↗

Asymmetry of forearm rolling as a sign of unilateral cerebral dysfunction.

We compared the reliability of asymmetry of forearm rolling (rotation of one forearm around the other in front of the torso) as a sign of unilateral cerebral dysfunction with that of other standard clinical tests. We studied 62 patients with radiologically confirmed unilateral cerebral lesions and 20 control subjects with normal imaging. Asymmetric forearm rolling was the most sensitive indicator of unilateral hemispheric disease (85%). This simple test is a useful addition to the neurologic examination.

Adult↗