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C J Russell

Publications and source records attributed to C J Russell.

At least 19 recordsLinked to original sources

Temperature dependence of polypeptide partitioning between water and phospholipid bilayers.

Various thermodynamic forces (e.g., the hydrophobic effect, electrostatic interactions, peptide immobilization, peptide conformational changes, "bilayer effects," and van der Waals dispersion forces) can participate in the transfer of polypeptides from aqueous solution into lipid bilayers. To investigate the contributions of these forces to peptide-membrane thermodynamics, we have studied the temperature dependence of the water-bilayer partitioning of 4 polypeptides derived from the first 25 amino acid residues in the presequence of subunit IV of yeast cytochrome c oxidase (Cox IVp) using electron paramagnetic resonance spectroscopy. The partitioning of the Cox IVp peptides into phospholipid bilayers increases as the temperature is increased from 3 to 40 degrees C. The contribution of bilayer surface expansion to the temperature-dependent partitioning is estimated to be relatively small and to contribute minimally to the increased bilayer binding of the peptides with increasing temperature. Thermodynamic analysis of the data shows that the transfer of the peptides from water into bilayers at 298 K is driven by the entropic term (-T delta Str) with values ranging from -6.7 to -10 kcal mol-1, opposed by the enthalpic term (delta Htr) by approximately 4 kcal mol-1, and accompanied by a change in heat capacity (delta Cp) ranging from -117 to -208 cal K-1 mol-1. Our results indicate that while a variety of forces do, in fact, contribute to the transfer free energies (delta Gtr), the major driving force for the water-to-bilayer transfer is the hydrophobic effect.

Amino Acid Sequence

Direct determination of the membrane affinities of individual amino acids.

Amino acids have distinct lipid bilayer affinities which influence the insertion and topology of membrane-bound polypeptides and proteins. To measure membrane affinities, 14 uncharged amino acids were introduced individually at a guest site in a 25-residue peptide derived from the membrane-binding presequence of yeast cytochrome c oxidase, and the peptides were labeled with a nitroxide spin-label. The free energies of transfer from phospholipid bilayers to water (delta delta Gbilayer) were determined directly by examination of partitioning into phospholipid bilayers using electron paramagnetic resonance. The delta delta Gbilayer values are in agreement with hydrophobicities assessed from 1-octanol-water partitioning of N-acetyl amino acid amides [Fauchere, J.-L., & Pliska, V. (1983) Eur. J. Med. Chem. 18, 369-375; Eisenberg, D., & McLachlan, A. (1986) Nature 319, 199-203] and quantitatively demonstrate the role of the hydrophobic effect in membrane-protein interactions.

Amino Acid Sequence

Moderated regression analysis and Likert scales: too coarse for comfort.

One of the most commonly accepted models of relationships among three variables in applied industrial and organizational psychology is the simple moderator effect. However, many authors have expressed concern over the general lack of empirical support for interaction effects reported in the literature. We demonstrate in the current sample that use of a continuous, dependent-response scale instead of a discrete, Likert-type scale, causes moderated regression analysis effect sizes to increase an average of 93%. We suggest that use of relatively coarse Likert scales to measure fine dependent responses causes information loss that, although varying widely across subjects, greatly reduces the probability of detecting true interaction effects. Specific recommendations for alternate research strategies are made.

Adult

Gene probe analysis in an informative family with multiple endocrine neoplasia syndrome type 2A (MEN 2A). Improvement in carrier risk estimation.

Gene probe analysis of the MEN 2A locus on chromosome 10 has been undertaken using the markers TB10.163, RBP 3 and TB14.34 in a large kindred with familial medullary thyroid carcinomas, with or without phaeochromocytomas or primary hyperparathyroidism. A maximum LOD score of 2.97 gave strong evidence of close linkage with zero recombination. For 12 members of the family so far not known to be affected by any form of the disease the estimated risk of carrying the gene has been considerably decreased in all but one, whose risk has been greatly increased.

Adolescent

MEN 2A: update on the Northern Ireland and Australian family.

The Northern Ireland/Australian family with multiple endocrine neoplasia type 2A (MEN 2A) originally described in 1987 is presented with a revised and enlarged pedigree. Four members of the first generation studied have died. A seventh member of the second generation studied has developed medullary thyroid carcinoma and has progressed to surgery. None of the third generation members studied has shown any conclusive abnormality in metabolic screening tests. Each member of the third and fourth generations has had genetic counseling and (if appropriate) DNA analysis with gene probes close to the MEN 2A gene locus on chromosome 10. All members of this highly penetrant family have remained asymptomatic for their disease.

Adult

Automatic postural responses in the cat: responses of hindlimb muscles to horizontal perturbations of stance in multiple directions.

The effect of the direction of unexpected horizontal perturbations of stance on the organization of automatic postural responses was studied in cats. We recorded EMG activity in eight proximal and distal muscles of the hindlimb along with vertical forces imposed by the limbs in awake behaving cats while they stood on an hydraulic platform. Postural responses to motion of the platform in 16 different horizontal directions were recorded. Vertical force changes were consistent with passive shifts of the center of mass and active correction of stance by the animals. When the perturbation was in the sagittal plane, vertical force changes began about 65 ms following initial platform movement. When the perturbation contained a component in the lateral direction, latency for vertical force changes was about 25 ms and an inflection in the vertical force trace was observed at 65 ms. No EMG responses were observed with latencies that were short enough to account for the early force component and it was concluded that this force change was due to passive shifts of the center of mass. The amplitude of the EMG responses of each muscle recorded varied systematically as perturbation direction changed. The directions for which an individual muscle showed measurable EMG activity were termed the muscle's "angular range of activation." No angular range of activation was oriented strictly in the A-P or lateral directions. Most muscles displayed angular ranges of activation that encompassed a range of less than 180 degrees. Onset latencies of EMG responses also varied systematically with perturbation direction. The amplitude and latency relationships between muscles, which made up the organization of postural responses, also varied systematically as perturbation direction was changed. This result suggests that direction of perturbation determines organizational makeup of postural responses, and for displacements in the horizontal plane, is considered a continuous variable by the nervous system.

Animals

Automatic postural responses in the cat: responses of proximal and distal hindlimb muscles to drop of support from a single hind- or forelimb.

Cats respond to drop of the support from beneath a single limb with the "diagonal stance response" (Coulmance et al. 1979). They load the limbs on the diagonal opposite to the one containing the dropped limb and unload the third supporting limb in the diagonal containing the dropped limb. Characteristic biomechanical delays in limb motion and in vertical force changes imposed upon the limbs are observed. These delays range from 30 to 45 ms, depending upon the location of the dropped limb. This study describes the kinematics of the "diagonal stance response" and the activation of selected agonist-antagonist muscle pairs acting on the joints of the hindlimb during the response. Proximal and distal hindlimb muscles respond to perturbations in groups that are appropriate to the vertical forces imposed upon the limb. When the hindlimb containing the recording electrodes is loaded by drop of the contralateral hindlimb or the ipsilateral forelimb medium latency (25-45 ms) EMG responses occur in the extensors. This response serves to stiffen the limb against the increased vertical force of loading. A similar response is observed when the hindlimb is reloaded after being dropped. In this case, however, short latency responses precede the medium latency responses in muscles that are passively stretched by the limb drop. When drop of the diagonal forelimb unloads the hindlimb containing the electrodes, medium latency responses are observed in the distal hindlimb flexors, which indicates that the unloading is evoked in part by active lifting of the limb. In most cases, the medium latency responses precede or are coincident with the changes in force imposed on the limb, suggesting that the observed responses are centrally programmed.

Animals

Automatic postural responses in the cat: responses of distal hindlimb muscles to paired vertical perturbations of stance.

The active components of the quadrupedal diagonal stance response to rapid removal of the support from beneath a single limb were studied in cats to further define the mechanisms that trigger and generate the response. We recorded EMG activity from lateral gastrocnemius and tibialis anterior muscles in awake, behaving cats while they stood on an hydraulic posture platform. By dropping the support from beneath a single limb, we evoked the diagonal stance response, with its characteristic changes in vertical force and EMG patterns. As the animal responded to this drop, a second perturbation of posture was then presented at intervals of 10 to 100 ms following the first. The second perturbation, which consisted of dropping the support from beneath the two limbs that were loaded as a result of the initial limb drop, made the first response biomechanically inappropriate. The EMG responses observed in both muscles during paired perturbations were triggered by the somatosensory events related to the perturbations. Muscle responses that were appropriate for the first perturbation always occurred with amplitudes and latencies similar to control trials. This was true even when the second perturbation occurred 10-20 ms after the first, that is, when this perturbation either preceded or was coincident with the response to the initial limb drop. The EMG responses that were normally associated with the second perturbation were delayed and/or reduced in amplitude when the time interval between perturbations was short. As the inter-perturbation interval was lengthened beyond 60-100 ms, however, EMG responses to the second perturbation were unaffected by the occurrence of the first perturbation. When the hindlimb containing the recording electrodes was dropped as part of the second perturbation, a myotatic latency response was observed in tibialis anterior. The amplitude of this response to the second perturbation was greater than controls when this displacement was presented during the period between initiation of the first perturbation and execution of the response to it. When the second displacement was presented after execution of the first response began, the amplitude of the myotatic response was reduced below control levels. While the results do not preclude the possibility that these "automatic" postural responses are segmental or suprasegmental reflexes, they support the hypothesis that the active component of the response to drop of the support beneath a single limb is centrally programmed and that the appropriate response can be triggered very rapidly by the somatosensory information signalling the perturbation.

Animals

Mobile coronary care and community mortality from myocardial infarction.

Over a 15-month period all episodes of suspected myocardial infarction were documented in two similar communities in Northern Ireland. The hospital coronary-care facilities were similar but only one area had a mobile coronary-care service. The incidence of myocardial infarction was similar in the two areas but the community mortality at 28 days was lower in all age-groups in the area served by the mobile unit. The difference in mortality was more pronounced in younger age-groups. Among those aged less than 65 the mortality rates in the two areas were 55% and 34%. The treatment in the two areas differed only in that it was provided about 2 h earlier where mobile care was available. The results suggest that the impact of early pre-hospital coronary-care on community mortality has been seriously underestimated.

Adult

Automatic postural responses in the cat: responses to headward and tailward translation.

EMG responses, vertical and A-P shear forces and kinematics of "automatic postural responses" to unexpected translational perturbations in the headward and tailward directions were studied in cats. Muscles acting on the major joints of the forelimbs and hindlimbs were studied. Movement of the animals in response to perturbation were highly stereotyped and consisted of two phases: (1) motion of the feet during platform movement while the trunk remained relatively stationary followed by (2) active correction of posture by movement of the trunk in the direction of perturbation. Vertical force changes occurred after the perturbation was well underway (latency 65 ms) and were related to the displacement of the center of mass and active correction of trunk position. Shear forces showed both passive (inertial) and active components and suggested that the majority of the torque necessary for postural correction was generated by the hindlimb. EMG responses in forelimb and shoulder muscles were most correlated with increase in vertical force, showing a generalized co-contraction in tailward translation (when these limbs were loaded) and little activity when the forelimbs were unloaded. EMG responses in hindlimb showed reciprocal activation of agonists and antagonists during perturbation with strong synergies of thigh and foot flexors in tailward translation and thigh and foot extensors in headward translation. The forelimb EMG patterns were most consistent with the conclusion that the forelimb is used primarily for vertical support during perturbation. It was concluded that hindlimb EMG responses were appropriate for both vertical support and performance of the postural correction. The hindlimb muscle synergies observed during translation are the "mirror image" of those observed in humans by other workers.

Animals

Maintaining control.

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Interprofessional Relations

Central connections of the posterior lateral line lobe in mormyrid fish.

Primary electroreceptor afferents terminate in the posterior lateral line lobe (PLLL) in electroreceptive teleosts. This paper examines the central connections of PLLL in fish of the family Mormyridae using horseradish peroxidase and tritiated amino acid tracing techniques. Some connections of the closely related lobus caudalis of the cerebellum are also examined. There are three zones on each side of the mormyrid PLLL cortex. Two receive input from mormyromast receptors, and one from ampullary receptors. An intrazonal projection system, intrinsic to PLLL, connects neighboring points within each zone. It also joins corresponding zones on the two sides of the body via commissural fibers. An interzonal system connects the two mormyromast zones on the same side of the midline. Central structures which project to PLLL include lobus caudalis, nucleus paratrigeminalis lateralis, and nucleus praeeminentialis. Nucleus praeeminentialis projects bilaterally and somatotopically to the lower molecular layer of PLLL. PLLL cortex projects bilaterally and somatotopically to two major mesencephalic sites: n. praeeminentialis, and n. lateralis. Somatotopically corresponding points in each zone of PLLL cortex project to the same small region of n. lateralis. Nucleus lateralis has a large and somatotopically organized projection to n. praeeminentialis. The afferent and efferent connections of lobus caudalis are similar to those of PLLL, indicating its close association with the electrosensory system. The anatomical results show that there is ample opportunity for electrosensory information arising on left and right sides of the body to interact centrally. One can suggest that comparison of afferent input from the two sides would reduce the non-significant variability which affects both of them equally. The results also show the presence of several somatotopically organized feedback lops which return the results of higher order processing of electrosensory information to earlier stages.

Afferent Pathways

Electrosensory pathways to the valvula cerebelli in mormyrid fish.

The valvula cerebelli of mormyrid fish has been implicated in the electroreceptive capabilities of these animals. This study uses peroxidase and tritiated amino acid tracing techniques to examine the pathways by which electroreceptive information gains access to the valvula. Ampullary and mormyromast receptor information reaches the medial and ventrolateral portions of the valvula by means of a large, direct projection from n. lateralis, part of the midbrain electrosensory area. In addition, smaller indirect n. lateralis-valvular projections travel via a pretectal nucleus and the so-called postventral thalamic nucleus, Knollenorgan receptor information ends in the dorsolateral portion of the valvula. A small, relatively direct pathway runs via n. medialis ventralis, but most Knollenorgan information appears to travel via an indirect system involving n. extrolateralis pars posterior and n. isthmi. The lateral line processing areas of the valvula project back onto many of the midbrain electrosensory nuclei. These results indicate that much of the cerebellum of this family is devoted to sensory processing rather than motor functions.

Afferent Pathways

Effects on exercise tachycardia during forty-eight hours of a series of doses of atenolol, sotalol, and metoprolol.

Beta adrenoceptor blockers differ mainly in their plasma elimination half-lives (t 1/2 s). It has been assumed that drugs with longer t 1/2 will have a longer duration of effect on exercise tachycardia. Several factors may influence the duration of action of beta blockers; we have investigated the contribution of plasma elimination t 1/2 and dose by comparing the effects on an exercise tachycardia in healthy subjects of placebo, 25, 50, 100, and 200 mg of atenolol and of sotalol, and 50, 100, 200, and 400 mg metoprolol. Subjects exercised before and at 2, 3, 6, 8, 24, 33, and 48 hr after oral doses of each drug. Plasma samples for measurement of drug concentration were drawn before each exercise period. Twenty-four hours after 50, 100, and 200 mg atenolol and 50, 100, 200, and 400 mg sotalol there were reductions in an exercise tachycardia; at this time reductions were greater after the larger doses. The plasma elimination t 1/2s of atenolol were between 7.2 +/0 1.0 hr. Although 50, 100, and 200 mg metoprolol induced the same reductions in an exercise tachycardia 2 hr after drug as 25, 50, and 100 mg atenolol and 50, 100, and 200 mg sotalol, these doses were without effect at 24 hr. Metoprolol 400 mg reduced exercise tachycardia at 24 hr but the effect was less than that of the three largest doses of atenolol and sotalol. The plasma elimination t 1/2 for metoprolol was between 3.6 +/- 0.6 and 5.0 +/- 1.8 hr. These results show that duration of cardiac beta blocking of cardiac beta blocking activity of atenolol, sotalol, and metoprolol is determined by the elimination t 1/2 and dose.

Adolescent

Observation on the efficacy and pharmacokinetics of betaxolol (SL 75212), a cardioselective beta-adrenoceptor blocking drug.

1 Observations were made in five subjects who exercised before and at 2, 3, 6, 8, 24, 33 and 48 h after the oral administration of placebo and 5, 10, 20 and 40 mg betaxolol. 2 The exercise heart rate remained constant at all times after the placebo. All doses of betaxolol significantly reduced the exercise tachycardia at all times. The maximum effect (34.4 +/- 2.2%) occurred after 40 mg. 3 There was a small decline in effect from the peak to 24 h when 40 mg produced a 23.3 +/- 2.7% reduction and a further decline to 48 h when there was a 14.6 +/- 1.8% reduction. 4 Plasma levels of betaxolol were measured in these studies. The peak plasma concentration occurred between 3 and 8 h with different doses. The plasma elimination half-lives after 10, 20 and 40 mg were 11.4 +/- 2.5, 15.9 +/- 4.9 and 15.1 +/- 3.1 h. 5 The effects of 40 mg betaxolol, 200 mg atenolol, 160 mg propranolol, 160 mg oxprenolol, 400 mg sotalol and placebo on an exercise tachycardia were compared in five subjects who received all treatments in random order. 6 There was no significant difference in the maximum reduction produced in an exercise tachycardia by the different drugs. 7 The effect of all drugs decreased with time. The effect of oxprenolol had worn off at 24 h but at 48 h only atenolol and betaxolol produced significant reductions in the exercise tachycardia. 8 Plasma concentrations of the different drugs were measured and plasma elimination half-lives determined. The half-life for betaxolol was 24.5 h which was longer than that for any of the other drugs. 9 These observations show that betaxolol is a potent beta-adrenoceptor antagonist with a long duration of effect on an exercise tachycardia and a long plasma elimination half-life.

Adrenergic beta-Antagonists