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Biomedical subjects

R A Baker

Publications and source records attributed to R A Baker.

At least 19 recordsLinked to original sources

Erythromycin and motilin stimulate sphincter of Oddi motility and inhibit trans-sphincteric flow in the Australian possum.

The actions of erythromycin lactobionate and porcine motilin on trans-sphincteric flow and simultaneous sphincter of Oddi motility were studied in 15 anaesthetized Australian Brush-tailed possums (Trichosurus vulpecula). Erythromycin (25-200 micrograms/kg) and motilin (25-200 ng/kg) were administered as graded doses by close intraarterial injection. Trans-sphincteric flow was measured as inflow and outflow. Both motilin and erythromycin decreased trans-sphincteric inflow (both P < 0.0001) and outflow (P < 0.0001 and P = 0.0017 respectively) in a dose-dependent manner. The highest dose of each agent abolished trans-sphincteric flow. These agents increased sphincter of Oddi phasic contraction frequency and basal pressure up to 2 and 3 fold respectively (P < 0.05). The amplitude of the sphincter of Oddi phasic contractions were not influenced in any consistent fashion by either agent. The durations of the responses (trans-sphincteric inflow) elicited by erythromycin and motilin were dose dependent (P = 0.0225 and P = 0.0001 respectively). The actions of erythromycin (200 micrograms/kg) or motilin (100 ng/kg) on trans-sphincteric flow and sphincter of Oddi motility were not influenced by neural blockade with tetrodotoxin. These findings support the hypothesis that erythromycin acts as a motilin agonist and both substances increase the resistance to flow through the sphincter of Oddi by raising the basal pressure and frequency of contractions.

Animals

Motilin and erythromycin enhance the in vitro contractile activity of the sphincter of Oddi of the Australian brush-tailed possum.

Erythromycin has been shown to interact with gastrointestinal smooth muscle in a similar manner to motilin, and has been postulated as a motilin receptor agonist. We report that in isolated preparations from the biliary tract of thirty one Australian Brush-tailed Possums (Trichosurus vulpecula) erythromycin acts in a similar manner to motilin. In all muscle strips from the sphincter of Oddi, prepared in both the circular and longitudinal orientation, both synthetic porcine motilin (10(-10) M-10(-6) M) and erythromycin (lactobionate) (10(-8) M-10(-4) M) stimulated contractile activity in a concentration dependent manner, via a direct effect on the smooth muscle (the response was unaffected by tetrodotoxin, omega conotoxin GVIA or atropine). In strips prepared from the gallbladder neither agonist affected the contractile activity in 7 of 8 animals. Motilin was approximately 1000 fold more potent in stimulating contractile activity than erythromycin in both sphincter of Oddi circular strips [pD2 for peak response to motilin 8.67 (mean) +/- 0.06 (SEM) compared with erythromycin 5.67 +/- 0.09] and sphincter of Oddi longitudinal strips [pD2 for peak response to motilin 8.64 (mean) +/- 0.28 (SEM) compared with erythromycin 5.45 +/- 0.23]. The concentration response curves for motilin and erythromycin were similar and both agonists required the presence of extracellular calcium to elicit responses (responses were diminished by verapamil and abolished in calcium free Krebs solution). Our results support the hypothesis that erythromycin mimics the action of motilin in stimulating the sphincter of Oddi in vitro.

Animals

Sphincter of Oddi regulates flow by acting as a variable resistor to flow.

Two models of transsphincteric flow and a model evaluating pumping activity were established in the anesthetized Australian brush-tailed possum to determine whether the sphincter of Oddi (SO) acts as a resistor or as a pump. A simple model of transsphincteric flow (inflow only) demonstrated that at physiological common bile duct (CBD) pressure, 9.5 +/- 0.3 cmH2O (n = 7), transsphincteric flow occurred between SO pressure waves (n = 10). A second more complex transsphincteric flow model was established that permitted simultaneous measurements of inflow, outflow, CBD pressure, SO basal pressure, SO contraction frequency, and amplitude. At physiological CBD pressure, inflow always equaled outflow (157.0 +/- 11.2 and 156.4 +/- 11.4 microliters/min, respectively; n = 7). The SO displayed regular contractions superimposed on a basal pressure of 1.1 +/- 0.4 mmHg. Contraction amplitude was 12.6 +/- 3.0 mmHg and the frequency was 3.6 +/- 0.4 contractions/min (n = 7). Pressure waves recorded in the CBD corresponded to the SO contractions and reflected SO activity. Transsphincteric flow occurred between SO contractions and was obstructed by these contractions. Stimulation of SO activity (basal pressure and contraction frequency) with intra-arterial injections of motilin (200 ng/kg) or erythromycin (200 micrograms/kg) abolished transsphincteric flow. Reduction in SO contraction frequency to 72.7 +/- 7.2% (P < 0.01, paired t test) after administration of Cisapride (2 mg/kg iv) increased transsphincteric flow to 147.6 +/- 12.3% (n = 7, P < 0.05, paired t test). In six possums, possible SO pumping action was evaluated. A manometer was connected to the CBD, and a second manometer was connected to the duodenum surrounding the papilla.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Neurotransmitter-specific uptake and retrograde transport of [3H]glycine from the inferior colliculus by ipsilateral projections of the superior olivary complex and nuclei of the lateral lemniscus.

Neurotransmitter-specific uptake and retrograde axonal transport of [3H]glycine were used to identify glycinergic projections to the inferior colliculus in chinchillas and guinea pigs. Six h after injection of [3H]glycine in the inferior colliculus, autoradiographically labeled cells were found ipsilaterally in the ventral nucleus of the lateral lemniscus, the lateral superior olive and the dorsomedial periolivary nucleus. These 3 regions accounted for 95% of the labeled projection neurons, with the remainder scattered elsewhere in the ipsilateral superior olivary complex. No labeled cells were found contralaterally even after survival times as long as 24 h. Retrograde transport of HRP from the inferior colliculus in these same cases confirmed the presence of additional projections that did not accumulate [3H]glycine. These included ipsilateral projections from the medial superior olive and cochlear nucleus and contralateral projections from the inferior colliculus, dorsal nucleus of the lateral lemniscus, lateral superior olive, periolivary nuclei and cochlear nucleus. The results implicate uncrossed projections from the ventral nucleus of the lateral lemniscus, lateral superior olive, and dorsomedial periolivary nucleus as the principal sources of inhibitory glycinergic inputs to the inferior colliculus.

Animals

The cervical myelopathy associated with rheumatoid arthritis: analysis of patients, with 2 postmortem cases.

The clinical findings in a group of 32 rheumatoid patients with symptomatic myelopathy are described. The myelopathy appeared in late middle age after many years of rheumatoid disease (average duration, 18 years). The most common radiological abnormality was anterior subluxation of C1. Other patterns occurred in about half the cases. The most common neurological findings were those of a mild to moderate spastic paraplegia, often with atrophy of muscles of the hands and sensory changes in the hands. Symptoms originating above the foramen magnum (nystagmus, diplopia, slurred speech) appeared to have a vascular cause and were sometimes associated with upward as well as posterior movement of the odontoid process. Root pain into the arms was not present, and its absence helped to distinguish these disorders from cervical spondylosis. Root pain into the territory of the C2 root was common. Medical or conservative therapy was not effective, and the preferred approach was use of a halo traction device followed by posterior fusion, with or without laminectomy. Pathologically, in 2 autopsy cases, the maximal change had occurred in the central gray matter and adjacent posterior and lateral columns. We postulate that direct pressure caused intermittent compression and narrowing of distal transverse branches of the anterior spinal artery.

Arthritis, Rheumatoid

Neuropathologic basis of computed tomographic scan abnormalities: a correlative method.

The accuracy of CT scan diagnosis can best be studied by comparing the postmortem scan to the corresponding pathologic specimen. To be valid, this comparison must be made in a precise manner: the CT image plane and the pathologic slice plane must correspond anatomically and must be juxtaposed in a specific point-to-point manner. A new method is described which correlates postmortem CT scans and postmortem pathologic specimens. Also considered are the utility and the limitations of matching CT absorption values to homogeneous pathologic lesions such as neoplasms, infarcts, hemorrhage and edema.

Brain

Metrizamide epidurography in dogs.

Metrizamide, a non-ionic water-soluble contrast agent, was injected into the epidural spaces of 6 dogs to see if the posterior border of the L7-S1 interspace could be outlined. Between two and six Metrizamide epidurograms were obtained on each dog. The L7-S1 interspaces were usually well outlined. No complications were experienced by the dogs. The dogs were sacrificed at intervals between 3 days and 42 days following their last epidurogram in order to examine the epidural tissues for inflammatory changes. No histologic differences were observed between the control and experimental dogs.

Animals

Metrizamide ventriculography and computed tomography in lesions about the third ventricle.

Metrizamide ventriculography was used in 24 patients with suspected lesions in and near the third ventricle. The diagnoses were aqueduct stenosis (6), upper brain stem expansions (5), third ventricular tumors (6), craniopharyngiomas (2), subarachnoid cyst (1) and normal (1). Computed tomography was used as the guide to predict the likely causes of obstruction and to determine if ventricular shunting was appropriate before or after ventriculography. Several cases required pneumoencephalography in combination with ventriculography in order to determine whether an upper brain stem lesion was intrinsic or extrinsic.

Adolescent

Sequelae of metrizamide myelography in 200 examinations.

Twenty pediatric and 180 adult patients underwent myelography using metrizamide (Amipaque). All patients were examined and interviewed before and after the studies. New or exacerbated symptoms attributed to metrizamide myelography were graded according to severity. After the procedure, 51 of 200 patients were unchanged from baseline. Headache was the most common complaint, with an overall incidence of 62%. Nausea and/or vomiting occurred in 38%. Back or leg pain, neck stiffness, temperature elevation, and a variety of less common manifestations were also observed. The incidence of sequelae was higher than in comparable Scandinavian studies with this contrast medium.

Adolescent

Myelography with metrizamide in infants and children.

Myelography with metrizamide (Amipaque) was performed in 46 infants and children. The contrast medium was rated as excellent. The examinations demonstrated more anatomic detail than is available from either myelography with oily contrast media or gas alone. The adverse reactions were at acceptable clinical levels.

Adolescent

Ventriculography with metrizamide in children.

Experiences from 24 ventriculographies with metrizamide (Amipaque) in children are reported. The dose used was 3 to 6 ml 200 mg I/ml in most cases. Ventriculography with metrizamide has been most useful for evaluating obstructive lesions related to the aqueduct or within the third ventricle. The large volume may be required in cases with great ventricular dilatation. Polytomography is a useful addition in many cases but it is not a constant requirement.

Adolescent

Gas myelography.

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Adolescent

Light-driven proton translocations in Halobacterium halobium.

The purple membrane of Halobacterium halobium acts as a light-driven proton pump, ejecting protons from the cell interior into the medium and generating electrochemical proton gradient across the cell membrane. However, the type response of cells to light as measured with a pH electrode in the medium consists of an initial net inflow of protons which subsides and is then replaced by a net outflow which exponentially approaches a new lower steady state pH level. When the light turned off a small transient acidification occurs before the pH returns to the original dark level. We present experiments suggesting that the initial inflow of protons is triggered by the beginning ejection of protons through the purple membrane and that the initial inflow rate is larger than the continuing light-driven outflow. When the initial inflow has decreased exponentially to a small value, the outflow dominates and causes the net acidification of the medium. The initial inflow is apparently driven by a pre-existing electrochemical gradient across the membrane, which the cells can maintain for extended times in the absence of light and oxygen. Treatments which collapse this gradient such as addition of small concentrations of uncouplers abolish the initial inflow. The triggered inflow occurs through the ATPase and is accompanied by ATP synthesis. Inhibitors of the ATPase such as N,N'-dicyclohexylcarbodiimide (DCCD) inhibit ATP synthesis and abolish the inflow. They also abolish the transient light-off acidification, which is apparently caused by a short burst of ATP hydrolysis before the enzyme is blocked by its endogenous inhibitor. Similar transient inflows and outflows of protons are also observed when anaerobic cells are exposed to short oxygen pulses.

Bacteriorhodopsins

Energy coupling in the active transport of amino acids by bacteriohodopsin-containing cells of Halobacterium holobium.

Growth of Halobacterium halobium under illumination with limiting aeration induces bacteriorhodopsin formation and renders the cells capable of photophosphorylation. Cells depleted of endogenous reserves by a starvation treatment were used to investigate the means by which energy is coupled to the active transport of [14C]proline, -leucine, and -histidine. Proline was readily accumulated by irradiated cells under anaerobiosis even when the photophosphorylation was abolished by the adenosine triphosphatase inhibitor N,N'-dicyclohexylcarbodimiide (DCCD). The uptake of proline in the dark was limited except when the cells were allowed to accumulate adenosine 5'-triphosphate (ATP) by prior light exposure or by the oxidation of glycerol. DCCD inhibited this dark uptake. These findings essentially support Mitchell's chemiosmotic theory of active transport. The driving force is apparently the proton-motive force developed when protons are extruded from irradiated bacteriorhodopsin or by the dydrolysis of ATP by membrane adenosine triphosphatase. Carbonylcyanide m-chlorophenylhydrazone (CCCP), a proton permeant known to abolish membrane potential, was a strong inhibitor of proline uptake. Leucine transport was also apparently driven by proton-motive force, although its kinetic properties differed from the proline system. Histidine transport is apparently not a chemiosmotic system. Dark- or light-exposed cells show comparable initial rats of histidine uptake, and these processes were only partially inhibited by DCCD or CCCP. The histidine system apparently does not utilize ATP per se since comparable rates of uptake were exhibited by cells of differing intracellular ATP levels. Irradiated cells did effect a greater total accumulation of histidine than dark-exposed cells. These findings suggest that ATP is needed for sustained transport.

Adenosine Triphosphatases

Medullary arteries in cerebral neoplasms.

In cerebral neoplasms, the visibility of long segments of the medullary arteries indicates white matter involvement by infiltrative or compressive disturbances. Relating the mass effect to the position of the medullary arteries should allow for differentiating a primary from a secondary avascular neoplasm. When the neoplasm is vascular, the presence of neovascularity with the medullary arteries is likely to signify a high degree of anaplasia.

Brain Neoplasms