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P Milner

Publications and source records attributed to P Milner.

At least 91 records · Page 5Linked to original sources

Revising RAWP.

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England↗

Serotonin is localized in endothelial cells of coronary arteries and released during hypoxia: a possible new mechanism for hypoxia-induced vasodilatation of the rat heart.

In this report we demonstrate the immunocytochemical localization of serotonin in endothelial cells of rat coronary vessels and a significant increase in the release of serotonin into the perfusate of Langendorff rat heart preparations during hypoxia. It is suggested that serotonin, localized in endothelial cells, is released during hypoxia and could provide part of a pathophysiological mechanism for vasodilatation to protect the heart from damage due to hypoxia.

Animals↗

Increased density of perivascular nerves to the major cerebral vessels of the spontaneously hypertensive rat: differential changes in noradrenaline and neuropeptide Y during development.

Fluorescence and immunohistochemical techniques were used to study the pattern and density of perivascular nerves containing noradrenaline (NA) and neuropeptide Y (NPY) supplying the major cerebral arteries of 4-, 6-, 8- and 12-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar (WIS) controls. Levels of NA and NPY in the superior cervical ganglia were measured. The density of nerves containing NA and NPY was greater in the hypertensive animals at all ages studied. However, the developmental changes in the density of innervation showed similar trends in both SHR and WIS groups. With few exceptions, there was a significant increase in the density of nerves containing NA from 4 to 6 weeks and from 8 to 12 weeks of age. This was in contrast to a low expression, and in some vessels a significant decrease in the number of NPY-containing nerves from 4 to 6 weeks. The density of nerve fibres containing NPY increased significantly in almost all vessels between 6 and 8 weeks of age and then stabilized. Thus there is a differential time course for the appearance of NA and NPY during development. Furthermore, the hyperinnervation of cerebral vessels in SHR by nerves containing NA and NPY precedes the onset of hypertension and associated medial hypertrophy. High-performance liquid chromatography and enzyme-linked immunosorbant assays show that the NA and NPY contents of the superior cervical ganglion do not reflect the changes in innervation pattern seen in the terminal fibres in the cerebral arteries. This tends to support the view that a local neurovascular mechanism is involved in the maintenance of hypertension. The possibility that increase in NPY as well as NA in cerebral perivascular nerves of hypertensive animals is involved in the protection of the blood-brain barrier against oedema and cerebral haemorrhage is raised.

Aging↗

Progressive changes in adrenergic, serotonergic, and peptidergic nerves in proximal colon of streptozotocin-diabetic rats.

The effect of progression of diabetes on adrenergic, serotonergic, and peptidergic innervation of the proximal colon of the rat at 8, 16, and 25 wk after induction of diabetes with streptozotocin was investigated using immunohistochemical, biochemical, and immunochemical methods. Two different responses to diabetes emerged from the present study. The first response, which involves noradrenaline and vasoactive intestinal peptide, was characterized by a sign of degeneration, where there was an initial increase in tissue level and immunoreactivity of the transmitters followed by a decrease in tissue level and density of nerve fibers at 16 and 25 wk after induction of diabetes. The second response, which involves 5-hydroxytryptamine, substance P, and calcitonin gene-related peptide, was characterized by changes in tissue level and immunoreactivity of the transmitters with no evidence of degeneration. The third feature was one of resistance to change due to diabetes, which was demonstrated by neuropeptide Y-containing nerves, where there was neither a change in tissue level of neuropeptide Y nor a change in immunoreactivity. It seems likely that the overall changes described will have profound implications in the function of the gut in the streptozotocin-diabetic rat model that may have some parallels in diabetic humans.

Animals↗

Increase in neuropeptide Y, but not noradrenaline, in the superior cervical ganglion of rabbits chronically exposed to cold.

We have investigated the effects of exposure to cold for 8 days on sympathetic neurones supplying the ear artery of the rabbit using a combination of assay and quantitative morphological techniques. The concentration of neuropeptide Y was shown to be significantly higher in the superior cervical ganglion of cold-exposed animals. Although the noradrenaline and dopamine levels in the ganglion were not significantly changed, the ratio of noradrenaline to dopamine was significantly increased after exposure to cold. The density of noradrenergic nerves supplying the ear artery was found to be unaffected by cold exposure. Since noradrenaline and neuropeptide Y have been shown to coexist in the majority of neurones of the superior cervical ganglion, the present study appears to provide an example of differential control of expression of neurotransmitters contained within the same neurone.

Animals↗

Direct evidence for concomitant release of noradrenaline, adenosine 5'-triphosphate and neuropeptide Y from sympathetic nerve supplying the guinea-pig vas deferens.

Concomitant release of noradrenaline (NA) (using tritium labelling), adenosine 5'-triphosphate (ATP) (using the luciferin-luciferase firefly technique) and neuropeptide Y (using the enzyme-linked immunosorbant assay) during electrical stimulation of the guinea-pig vas deferens has been demonstrated. In addition it has been shown: (1) that release of NA and ATP is unaffected following selective desensitization of the P2 (ATP)-purinoceptor by alpha, beta-methylene ATP and (2) that total block of contractile responses of the vas deferens to nerve stimulation by a combination of prazosin and alpha, beta-methylene ATP does not reduce the release of NA and ATP. These results are consistent with the hypothesis that NA, ATP and neuropeptide Y are released as co-transmitters or modulators in sympathetic nerves supplying the vas deferens.

Adenosine Triphosphate↗

Cerebral infarction in sickle cell anemia: mechanism based on CT and MRI.

We studied 25 patients with sickle cell anemia and cerebral infarction. We classified lesions as to probable mechanism (large versus small vessel disease) based on the CT/MRI appearance of established infarction. Most patients had CT/MRI patterns of major cerebral vessel occlusion (41%) or border-zone (distal insufficiency) infarcts (31%) best explained by large cerebral vessel vasculopathy. Seven of 25 (28%) had either isolated subcortical (12%) or small cortical branch occlusion (16%) consistent with other mechanisms such as small vessel occlusion or embolism. These results suggest that most clinically recognized cerebral infarctions in sickle cell anemia are caused by large vessel disease, but this mechanism may not account for symptoms of cerebral ischemia in all cases.

Adolescent↗

P0 myelin protein produces experimental allergic neuritis in Lewis rats.

P0 protein was prepared from bovine spinal root myelin. The purity was shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunostaining with affinity purified antisera. P0 in the presence of lysophosphatidylcholine induced paralysis and histological lesions resembling experimental allergic neuritis in Lewis rats. Lysophosphatidylcholine also enhanced the ability of P2 to produce neuritis. The conformation of these proteins may be important in determining their ability to induce experimental allergic neuritis. P0 deserves consideration as an antigen relevant to Guillain-Barré syndrome.

Animals↗

Histochemical and biochemical investigation of adrenergic, cholinergic and peptidergic innervation of the rat ventral prostate 8 weeks after streptozotocin-induced diabetes.

The gross anatomy and autonomic innervation of the ventral prostate glands was examined in control and streptozotocin-induced diabetic rats. The most striking finding was the consistent reduction in size and the gross atrophy of the prostates from diabetic rats. No change was detected in the total content of noradrenaline in the alveolar lobes or in the levels of vasoactive intestinal polypeptide, neuropeptide Y and substance P in the whole prostates of diabetic rats. However, histochemical and immunohistochemical investigations revealed localized reductions in density and/or fluorescence intensity of noradrenaline-containing nerve fibres and increased density and/or fluorescence intensity of vasoactive intestinal polypeptide- and neuropeptide Y-containing nerve fibres in the alveolar smooth muscle of a majority of diabetic animals. No changes in acetylcholinesterase-staining nerve fibres were seen. The adrenergic component of the autonomic nervous system in this gland appears to be particularly susceptible to change in diabetes.

Adrenergic Fibers↗

Neuropeptide Y- and vasoactive intestinal polypeptide-containing nerves in the intrinsic external urethral sphincter in the areflexic bladder compared to detrusor-sphincter dyssynergia in patients with spinal cord injury.

Specimens of urethra were obtained from patients with cervical and thoracic spinal cord lesion with detrusor-sphincter dyssynergia and from patients with lower motor neurone lesion with detrusor areflexia, undergoing transurethral sphincterotomy. Neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) in nerves associated with both the smooth and striated muscle components of the urethral sphincter were studied immunohistochemically and by immunoassay. In patients with detrusor-sphincter dyssynergia following cervical and thoracic spinal cord injury, NPY- and VIP-immunoreactive varicose nerve fibres were seen in both the smooth and striated muscle components of the urethral sphincter. In the smooth muscle, NPY- and VIP-immunoreactive nerves did not appear to have any particular orientation, but in the striated muscle region they were found to run along the length of individual muscle fibres. In patients with detrusor areflexia following lower motor neurone lesion, while the pattern, density and fluorescence intensity of NPY- and VIP-immunoreactive nerves in the smooth muscle of the sphincter mechanism appeared the same as seen in patients with detrusor-sphincter dyssynergia, there was a marked increase in the density of these nerves in the striated muscle region of the sphincter mechanism. Quantitation of the peptides by immunoassay was consistent with the histochemical findings, with significantly higher levels of both NPY and VIP in the striated muscle of patients with lower motor neurone lesion, compared to those with cervical and thoracic spinal cord lesion, p = 0.04. NPY and VIP levels in urethral smooth muscle were in the same range in lower motor neurone lesion patients and cervical and thoracic spinal cord lesion patients. We conclude that there are increased NPY- and VIP-containing fibres in striated muscle of the intrinsic external urethral sphincter in patients with areflexic bladder compared with those with detrusor-sphincter dyssynergia.

Adult↗

Standardization of four videotaped tests of speechreading ranging in task difficulty.

Repeated measures are needed to assess speechreading ability of prospective cochlear implant candidates and to follow their progress over the course of treatment. To perform such measures, high quality color videotaped versions of four speechreading tests were constructed using a male and a female speaker. Materials were selected to provide gradations in task difficulty ranging from responses to questions with the topic known, to verbatim repetition, to abstraction of information from a spoken paragraph in order to answer questions. The tests were: (1) NAL/West Haven modification; (2) Iowa-Keaster, Forms A and B; (3) CID Everyday Sentences; and (4) Gold Rush Paragraph. The tapes were standardized by presentation to young adult normal subjects. Results indicated that a range of performance could be measured by using the present tests as a battery, although the anticipated ranking of tests was not obtained.

Adolescent↗

Speaking rate of adventitiously deaf male cochlear implant candidates.

No objective group data on speaking rate or speaking duration have been reported on the speech of adventitiously profoundly hearing-impaired adults. Results of the present study showed that speaking rate, i.e., number of syllables per second, was significantly slower and speaking duration was significantly longer for 25 adventitiously profoundly hearing-impaired adult male cochlear implant candidates than for 10 normal-hearing control subjects. The factors of length of time since onset of profound hearing loss and hearing aid use did not significantly affect speaking rate. Based on these objective data, a rationale and method are presented for aural rehabilitation of the profoundly hearing-impaired who exhibit speaking rate abnormalities.

Adult↗

Endothelium-derived relaxing factor in cultured cells.

Many vasoactive agents stimulate release of an endothelium-derived relaxing factor (EDRF). EDRF stimulates cyclic guanosine 3',5'-monophosphate (cGMP) accumulation and relaxation of vascular smooth muscle in a manner similar to that produced by sodium nitroprusside. Endothelium and vascular smooth muscle were isolated from porcine, bovine, and rat thoracic aorta. The capacity of sodium nitroprusside to stimulate cGMP accumulation in cultured bovine, porcine, and rat vascular smooth muscle was found to increase with time in culture to a maximum of 12 to 14 days after plating. In addition, bovine and porcine vascular smooth muscle, but not rat vascular smooth muscle, lost the sodium nitroprusside-stimulated cGMP response after the fifth passage. Cultured endothelial cells did not respond to endothelium-dependent vasodilators or sodium nitroprusside with increased cGMP levels. Vascular smooth muscle cells responded only to sodium nitroprusside. Mixed cultures of porcine and bovine endothelium and vascular smooth muscle and bovine endothelium and rat vascular smooth muscle responded to endothelium-dependent vasodilators with increased cGMP levels. Short-term (4 hours) coculture experiments using bovine endothelium grown on microcarriers to assess the need for long-term contact between the two cell types produced similar results. Release of EDRF from bovine endothelium was studied by loading endothelium-covered microcarrier beads into a column superfused with physiological buffer. Treatment of the column with bradykinin, the calcium ionophore A23187, melittin, and arachidonate released EDRF from the column as measured by cGMP changes in denuded aortic rings and vascular smooth muscle cells and by relaxation of rings when bathed in column effluent. The time course of cGMP changes and relaxation were similar and could be reversed by hydroquinone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Voice intensity of prospective cochlear implant candidates and normal hearing adult males.

Voice intensity in 19 prospective cochlear implant candidates, all adventitiously profoundly sensorineurally deaf adult males, was investigated. For the first time with objective data, it was shown that such deaf subjects spoke with significantly increased voice intensity and with greater intensity fluctuations than normal hearing male speakers. Neither length of time of profound deafness nor history of hearing aid use significantly affected voice intensity. Based on quantitative data, rehabilitation of voice intensity problems in the adventitiously deaf is indicated.

Aged↗