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J E Fox

Publications and source records attributed to J E Fox.

At least 145 records · Page 8Linked to original sources

The mechanism of motilin excitation of the canine small intestine.

Close intraarterial injections of motilin to the small intestine of the anaesthetized dog produce prolonged phasic contractions. Tetrodotoxin infused intraarterially blocked field stimulated contractions and abolished the response to motilin as did treatment with a combination of hexamethonium and atropine. Atropine alone increased the dose of motilin required to induce responses. Hexamethonium alone similarly increased the dose of motilin required in the jejunum, but not for the ileum. These results suggest that motilin acts to contract small intestine by stimulation of intrinsic excitatory nerves, some of which are post-ganglionic cholinergic and some of which are not, but are activated by a pathway with a nicotinic synapse. The ED50 for ileal contractions was greater than that for the jejunum and the time to reach maximum contractions longer suggesting a decreased responsiveness of the lower small intestine to motilin as compared to the upper gastrointestinal tract. These results and the lesser quantity of immunoreactive motilin in the ileum than in the jejunum may explain the lack of relationship of the activity front of the migrating motor complex in the lower small intestine to venous motilin concentrations.

Animals↗

Actin filament content and organization in unstimulated platelets.

The extent of actin polymerization in unstimulated, discoid platelets was measured by DNase I inhibition assay in Triton X-100 lysates of platelets washed at 37 degrees C by gel filtration, or in Triton X-100 lysates of platelets washed at ambient temperatures by centrifugation in the presence of prostacyclin. About 40% of the actin in the discoid platelets obtained by either method existed as filaments. These filaments could be visualized by electron microscopy of thin sections. Similar results were obtained when the actin filament content of discoid platelets was measured by sedimentation of filaments from Triton X-100 lysates at high g forces (145,000 g for 45 min). However, few of these filaments sedimented at the lower g forces often used to isolate networks of actin filaments from cell extracts. These results indicate that actin filaments in discoid cells are not highly crosslinked. Platelets isolated by centrifugation in the absence of prostacyclin were not discoid, but were instead irregular with one or more pseudopodia. These platelets also contained approximately 40-50% of their actin in a filamentous form; many of these filaments sedimented at low g forces, however, indicating that they were organized into networks. The discoid shape of these centrifuged platelets could be restored by incubating them for 1-3 h at 37 degrees C, which resulted in the reversal of filament organization. High g forces were then required for the sedimentation of the actin. Approximately 80-90% of the actin in platelets washed at 4 degrees C was filamentous; this high actin filament content could be attributed to actin polymerization during the preparation of the platelets at low temperatures. These studies show that platelet activation involves mechanisms for the structural reorganization of existing filaments, in addition to those previously described for mediating actin polymerization.

Actins↗

Fractionation of guinea pig serum for an inducer of gonococcal resistance to killing by human serum: active fractions containing glucopeptides similar to those from human red blood cells.

The resistance of gonococci to complement-mediated killing by serum is important in the pathogenesis of gonorrhoea. Most urethal strains lose this resistance on subculture. The host product(s) which induces the resistance in vivo is therefore fundamental to pathogenesis. Human genital secretions and some sera induced gonococci to serum resistance in vitro. Guinea pig serum was more active than human serum and low molecular weight fractions from it conferred resistance to gonococci in 3 h at 37 degrees C. Similar active fractions were obtained from human sera. Now guinea pig serum has been further fractionated for the low molecular weight inducer by membrane filtration, gel filtration on Sephadex G25, high performance liquid chromatography (HPLC) with a Spherisorb ODS reverse phase column, chromatography on Sephadex LH20 and HPLC with a Partisil SCX cation exchange column. The small yield (less than 1 mg from 400 ml serum) of highly active material was contaminated with breakdown products from the Partisil SCX column and a mixture of compounds. However, analysis indicated the presence of one or more small glucopeptides containing cysteine, glutamic acid, aspartic acid, threonine, serine, glycine, alanine, valine and lysine. Similar glucopeptides are liberated from fresh human red blood cells in slightly hypertonic saline and samples of them induced gonococci to serum resistance.

Animals↗

Central conduction time following surgery for cerebral aneurysm.

Somatosensory evoked potentials have been recorded serially in 21 patients following aneurysm surgery. Central conduction time correlated reasonably well within the patient's clinical state at the time of testing, but it did not act as a useful predictor of clinical deterioration.

Adolescent↗

Neurotensin inhibition of canine intestinal motility in vivo via alpha-adrenoceptors.

Neurotensin given intra-arterially in bolus doses to the canine small intestine inhibited field-stimulated, atropine-sensitive contractile responses in the duodenum (mean effective dose (ED50) = 3.2 X 10(-11) mol) and in the ileum (mean ED50 = 2.1 X 10(-11) mol). Norepinephrine (ED50 = 3 X 10(-9) mol) also inhibited these contractile responses. Phenylephrine (ED50 = 1.3 X 10(-8) mol) was one-fourth as potent as norepinephrine and clonidine (ED50 = 8 X 10(-10) mol) was at least as potent as norepinephrine, while isoproterenol (up to 8 X 10(-8) mol) failed to show any inhibitory effects. Phentolamine (2 mg/kg) increased significantly the ED50 of neurotensin and norepinephrine. Prazosin (2 mg/kg) increased significantly the ED50 of norepinephrine in the duodenum but had no effect on the ED50 of neurotensin. Yohimbine (2 mg/kg) increased the ED50 values of neurotensin and adrenergic agonists. Both neurotensin and norepinephrine in doses causing maximal inhibition of field-stimulated responses decreased (by 40 to 60%) contractile responses to 9 X 10(-10) mol (approximately the intra-arterial ED50 dose) of acetylcholine. Reserpine pretreatment markedly diminished the inhibition of spontaneous or field-stimulated phasic contractions by distention or field stimulation of a distal site. Reserpine also diminished the ED50 for neurotensin from 1 X 10(-11) to 2 X 10(-11) mol (p less than 0.02), but did not abolish neurotensin's inhibitory effect. Tetrodotoxin (10-15 micrograms, intra-arterially) increased the dose of neurotensin required to inhibit spontaneous activity in the ileum but after this toxin, as after adrenergic antagonists or reserpine, maximal inhibition could still be obtained. These results suggested that neurotensin inhibited contractile activity of canine intestine by acting on neural receptors to release norepinephrine. Norepinephrine activated primarily alpha 2-adrenoceptors and ultimately inhibited acetylcholine release. Neurotensin also inhibited contractions by activating a second, less sensitive receptor on smooth muscle.

Acetylcholine↗

Structural basis for function of circular muscle of canine corpus.

The structural relationship of nerve, muscle, and interstitial cells of Cajal in circular muscle of the lesser curvature of the dog stomach (corpus) has been studied. This muscle has also been characterized functionally. Muscle cells are arranged in bundles and are interconnected by numerous gap junctions averaging 30 per 100 cross-sectioned muscle cells, and leading to an estimate that each cell has about 200 gap junctions. No other smooth muscle studied to date has such a high density of gap junctions. Nerve varicosities, mostly containing a predominance of small agranular vesicles with some containing a predominance of large granular vesicles, are located outside muscle bundles, usually in small- to medium-sized bundles. Very few nerves containing small granular vesicles, presumably adrenergic, were found in agreement with functional studies. A substantial number of damaged nerve profiles was also found, perhaps contributing to the loss of nerve-dependent responses present in vivo, but absent in vitro. Interstitial cells of Cajal were rare in this tissue, about 1 per 1000 cross-sectioned muscle cells. When present, they often made gap junction contact with smooth muscle and were closely innervated. The findings of a structural basis for very tight coupling between cells, the absence of a structural basis for direct neural control over motor function, and other findings have implications for the control of contractions in this muscle.

Animals↗