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Biomedical subjects

R Murphy

Publications and source records attributed to R Murphy.

At least 73 records · Page 4Linked to original sources

Pathway-specific connections between peptide-containing preganglionic and postganglionic neurons in the vagus nerve of the toad (Bufo marinus).

We have examined immunohistochemically the distribution of postganglionic nerve cell bodies and their preganglionic inputs in the vagus nerve of the toad, Bufo marinus. Nerve cell bodies containing immunoreactivity (IR) to somatostatin (SOM) were found at the origin of the oesophago-gastric ramus; these neurons projected to the lung. Cell bodies with SOM-IR also occurred in the intracardiac branches of the vagus, but were absent from the distal segments of the pulmonary and oesophageal rami of the vagus. Cell bodies with IR to vasoactive intestinal peptide (VIP) also occurred at the origin of the oesophago-gastric ramus, but most of these neurons projected to the oesophagus. Most neurons in the distal pulmonary and oesophageal rami were VIP-IR. Some nerve cell bodies in the vagosympathetic trunk and in the intracardiac rami contained both SOM-IR and VIP-IR. Vagal preganglionic nerve fibres with IR both to a somatostatin-like peptide and to substance P were associated exclusively with those postganglionic VIP-IR neurons that projected to the oesophagus. These results provide evidence for highly specific connections between immunohistochemically defined populations of preganglionic and postganglionic neurons in the vagus nerve.

Animals

Management of intraocular pressure during cardiopulmonary bypass.

Intraocular pressure was measured in two groups of patients undergoing cardiopulmonary bypass surgery. A control group received mannitol at the start of bypass in accordance with standard practice; pressure was found to rise by 6.4 mmHg. In a second group of patients mannitol was administered 30 min prior to bypass; pressure elevation of 2.4 mmHg was found. These findings are discussed in relation to other clinical observations during bypass and to ocular morbidity complicating bypass surgery.

Cardiopulmonary Bypass

Neuropeptide Y-like immunoreactivity is absent from most perivascular noradrenergic axons in a marsupial, the brush-tailed possum.

Noradrenergic perivascular axons were demonstrated in all systemic arteries and veins of a marsupial, the brush-tailed possum (Trichosurus vulpecula), by a catecholamine fluorescence procedure and with antisera directed against the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (D beta H). Perivascular axons with neuropeptide Y-like immunoreactivity (NPY-LI) were not found in most systemic arteries and veins using antisera which recognize NPY and other members of the pancreatic polypeptide family in diverse vertebrate species. The exceptions were the renal, coeliac, main mesenteric and iliac arteries, where up to 50% of axons with TH-LI or D beta H-LI also showed NPY-LI with two of the 4 antisera used. No noradrenergic nerve cell bodies in thoracic sympathetic ganglia had NPY-LI, whilst 3% of noradrenergic nerve cell bodies in lumbar sympathetic chain ganglia had weak NPY-LI. This marsupial is the first vertebrate species found to date in which the majority of perivascular noradrenergic axons do not contain NPY-LI. If these axons contain an as yet unidentified neuropeptide, it is unlikely to be closely related to NPY.

Animals

Innervation of the large arteries and heart of the toad (Bufo marinus) by adrenergic and peptide-containing neurons.

The innervation of the major arteries and heart of the toad (Bufo marinus) was examined by use of glyoxylic acid-induced catecholamine fluorescence and peptide immunohistochemistry. All arteries possessed a moderate to dense plexus of adrenergic axons, which also showed neuropeptide Y-like immunoreactivity (NPY-LI). Some adrenergic axons in the intracardiac vagal trunks showed NPY-LI, but the varicose adrenergic axons innervating the cardiac muscle of the atria and ventricle, and the coronary blood vessels did not display NPY-LI. About half of the nerve cell bodies in the anterior sympathetic chain ganglia with dopamine-beta-hydroxylase-LI (DBH-LI) also contained NPY-LI. The nerve cell bodies with DBH-LI alone were generally larger (median diameter 30 micron) than those with both DBH-LI and NPY-LI (median diameter 20 micron). Some cell bodies showing DBH-LI alone were surrounded by boutons with NPY-LI but not DBH-LI. Axons that displayed simultaneously both substance P-LI (SP-LI) and calcitonin gene-related peptide-LI (CGRP-LI) also formed a plexus around all arteries studied, being particularly dense around the mesenteric and pulmonary arteries. These axons are most likely sensory since SP-LI was reduced by capsaicin treatment, and nerve cell bodies with both SP-LI and CGRP-LI were found in dorsal root ganglia and the vagal ganglion. A dense plexus of axons showing somatostatin-LI was located around the pulmonary artery and its main intrapulmonary branches. A few nerves with vasoactive intestinal polypeptide-LI were found around the dorsal aorta and pulmonary artery. No perivascular nerves with enkephalin-LI were observed. Reversed-phase, high-pressure liquid chromatography of acid extracts of the large arteries showed that the major peaks of NPY-LI and SP-LI co-eluted with porcine NPY (1-36) and synthetic SP (1-11), respectively. Thus, the location and structure of these peptides in perivascular nerves has been highly conserved during vertebrate evolution.

Adrenergic Fibers

Partial depletion of neuropeptide Y from noradrenergic perivascular and cardiac axons by 6-hydroxydopamine and reserpine.

The effects of 6-hydroxydopamine (6-OHDA) and reserpine on the storage of neuropeptide Y (NPY) in noradrenergic cardiovascular nerves were examined with both immunohistochemistry and radioimmunoassay (RIA). Immunohistochemical double-labelling techniques demonstrated that NPY was located only in noradrenergic axons in the guinea-pig carotid artery, mitral valve, thoracic inferior vena cava, thoracic aorta, superior mesenteric artery and small saphenous vein. Treatment with 6-OHDA in vivo eliminated noradrenergic, NPY-containing axon terminals from all tissues, but preterminal axons were still prominent in the superior mesenteric artery. The greatest depletion of NPY detected by RIA after 6-OHDA treatment was found in tissues with a predominance of terminal noradrenergic axons, such as the small saphenous vein, whereas NPY accumulating in preterminal axons masked the loss of NPY from terminal axons in the superior mesenteric artery. After treatment with doses of reserpine that led to a rapid depletion of noradrenaline (NA) from perivascular nerves, NPY was still detected histochemically at all times although levels sometimes appeared to be reduced. RIA demonstrated that the partial depletion of NPY after reserpine consisted of a rapid phase seen in the vena cava and saphenous vein after the highest doses, and a slower phase of NPY depletion from all tissues after all doses of reserpine. The greatest depletion of NPY from terminal axons by reserpine (in small saphenous vein) was 85-90%. These results demonstrate that some NPY can be stored in noradrenergic perivascular axons in the absence of noradrenaline, but that partial depletion of NPY from axon terminals results when NA stores are depleted by reserpine. The variation in extent of NPY depletion between tissues after drug treatments can be explained by variation in the ratio of preterminal to terminal axons.

Animals

The significance of longitudinal excursion in peripheral nerves.

It has been shown that nerves do, in fact, have a longitudinal excursion. This excursion is accentuated during adjacent joint motion. It is important for the surgeon treating nerve injuries, compression lesions, and adherent nerves to realize that the restoration of the longitudinal excursion of the peripheral nerves must be accomplished in order to effectively treat the inciting lesion.

Cicatrix

Co-localization of neuropeptide Y, vasoactive intestinal polypeptide and dynorphin in non-noradrenergic axons of the guinea pig uterine artery.

Two major populations of perivascular axons containing immunoreactivity to neuropeptide Y (NPY) have been revealed in the main uterine artery of the guinea pig by immunohistochemical procedures which allow the simultaneous visualization of two antigens. One population contained immunoreactivity to dopamine-beta-hydroxylase (D beta H) and was presumably noradrenergic. The other main population of axons with NPY-like immunoreactivity (NPY-LI) did not have D beta H-like immunoreactivity (D beta H-LI) and was presumably non-noradrenergic. These non-noradrenergic axons also contained immunoreactivity to vasoactive intestinal polypeptide (VIP) and dynorphin (DYN). Indeed, nearly all axons with VIP-LI also contained NPY-LI and DYN-like immunoreactivity (DYN-LI). NPY constricted the uterine artery perfused in vitro, whilst VIP dilated uterine arteries preconstricted with noradrenaline or NPY. Thus, we have evidence for the coexistence of a vasoconstrictor peptide and a vasodilator peptide in the same non-noradrenergic perivascular axons, which also contain an opioid peptide, dynorphin.

Animals

Norepinephrine-dependent and independent mechanisms of persistent effects of amphetamine in rat cerebellum.

Previous studies of the effects of chronic low-dose amphetamine (2 mg/kg per day X 21 days) on the spontaneous discharge rate of cerebellar Purkinje neurons have shown persistent depressant effects for up to 50 days after cessation of drug administration. The depression of spontaneous discharge observed was only partially reversible by various pharmacological agents which disrupt noradrenergic neurotransmission in cerebellum. In the present study, several additional approaches were used to investigate further this persistent effect. Rats were treated, either before or after chronic treatment with amphetamine, with intracisternal 6-hydroxydopamine at doses which destroy most noradrenergic fibers in cerebellum. In either case Purkinje neurons were still significantly slowed after cessation of amphetamine treatment, although the depression was not as great as previously observed. In another experiment, cerebellar cortical levels of 3-methoxy, 4-hydroxy phenyl glycol (MHPG) were measured after cessation of amphetamine administration, to determine if there was biochemical evidence for increased noradrenergic neurotransmission. At ten days, MHPG levels were elevated by 36%, and they returned to control values by 30 days. The evidence obtained in these studies suggests that chronic amphetamine treatment causes a persistent increase in noradrenergic neurotransmission, but non-noradrenergic mechanisms may also be important mechanisms in the long-lasting depression of activity of cerebellar Purkinje neurons.

Amphetamine

Rating verbal communication impairment in schizophrenia and affective disorders.

Audio recordings of interviews with 42 psychiatric patients (10 schizophrenic, 11 manic, 11 schizoaffective, and 10 depressive patients) and 10 hospitalized orthopedic patients were rated for the presence of verbal communication impairment using the system developed by Andreasen. The definitions of some categories required additional qualifying statements before agreement could be reached on their meaning and applicability in specific circumstances. Nevertheless, the results indicate that the scales can be used reliably by carefully trained, nonprofessional raters. Significant differences were found between diagnostic groups with regard to the frequency and severity of some categories of communication impairment, but the general pattern of results supports previous suggestions that these problems are not pathognomonic of schizophrenia. Based on our experience, we suggest a few changes that might be helpful to other investigators, both in the procedures used for obtaining samples of speech and the definitions of subcategories of verbal communication impairment.

Child

Residues and metabolites of selected persistent halogenated hydrocarbons in blood specimens from a general population survey.

The National Center for Health Statistics collaborated with the National Human Monitoring Program of the U.S. Environmental Protection Agency (EPA) in a four-year study to assess the exposure of the general population to selected pesticides through analysis of blood serum and urine specimens. Specimens were collected on a national probability half-sample of persons 12-74 years of age from 64 locations across the United States comprising the sample areas in the Second National Health and Examination Survey (NHANES II) and analyzed for selected organochlorine, carbamate, chlorophenoxy and organophosphorus pesticides. Medical, nutritional and pesticide usage data are also available for each sample person. Results of the blood serum analyses indicate that the general population is being exposed to some of these types of pesticides. For selected pesticide residues, the percent quantifiable positives and median serum levels by age group are presented for three regions of the United States. Since 1970, EPA has conducted a national probability sampling of human adipose tissue. Specimens obtained on a survey design representative of the general population were analyzed for selected organochlorine pesticides and toxic chemicals. Findings from the 1979 survey also indicate exposure of the general population to some of these chemicals.

Adolescent

Measurement and chromatographic characterization of vasoactive intestinal peptide from guinea-pig enteric nerves.

The material exhibiting immunoreactivity for vasoactive intestinal peptide in guinea-pig enteric nerves has been characterized by high-performance liquid chromatography in three modes: reversed-phase, cation-exchange and gel permeation. In each case a major portion of the material contained in acetic acid extracts of guinea-pig gut showed the same chromatographic properties as the synthetic porcine peptide of defined amino acid sequence. It is therefore concluded that this immunoreactive material is authentic vasoactive intestinal peptide. The study illustrates a number of the problems encountered in attempting to characterize, and measure reliably, peptides in tissue extracts.

Animals

Time course of effect of capsaicin on ultrastructure and histochemistry of substance P-immunoreactive nerves associated with the cardiovascular system of the guinea-pig.

Capsaicin, a neurotoxin which depletes substance P from primary afferent nerve fibres, was injected systematically into adult guinea pigs. The effects of capsaicin were studied by immunohistochemistry, electron microscopy and radioimmunoassay at times from 5 min to 1 year. Within 5 min after a single injection of capsaicin (50 mg/kg) substance P immunofluorescence appeared less intense and less homogeneous than normal (i.e. it appeared granular). Large nerve trunks remained evident, but there were fewer fine single nerve fibres. With increasing time there was a progressive decrease in the number of immunoreactive fibres; by 4 h there was a marked reduction in the number of fibres and by 24 h only an occasional fibre was evident. In animals sacrificed 2 or more hours after treatment large brightly fluorescent swellings were seen in many nerves. Depletion of substance P-immunoreactivity persisted for as long as 365 days after treatment. Electron microscopy revealed alterations in capsaicin-sensitive nerve fibres within 5 min after treatment. Many fibres appeared swollen and there was disruption of their internal morphology, e.g. loss of microtubules and filaments and presence of an amorphous flocculent material in the axons. With increasing time after treatment, electron-dense profiles, indicative of degenerating nerve fibres, were commonly seen associated with Schwann cells. These findings demonstrate that the effects of systemic administration of capsaicin to adult guinea pigs occur rapidly in capsaicin-sensitive nerve fibres. The long lasting depletion of substance P-containing fibres is due to their degeneration.

Animals

Neuropeptides contained in peripheral cardiovascular nerves.

The neuropeptides, substance P, vasoactive intestinal peptide (VIP), neuropeptide Y and enkephalin have been found in nerves associated with the heart and blood vessels of a range of mammals, including man. There is also evidence for some cardiovascular nerves with gastrin releasing peptide and neurotensin immunoreactivity. Substance P is in sensory nerves with a widespread distribution to the heart and all vascular beds. In general, large arteries have the densest innervation and the density of nerves decreases as arterial size decreases. In adult guinea-pigs, an adequate treatment with capsaicin causes the degeneration of almost all cardiovascular substance P nerves. Using capsaicin as a tool it has been shown that the substance P containing sensory nerves are not essential for baroreceptor reflexes. VIP nerves also have a widespread distribution, being particularly prominent in the cerebral arteries, uterine arteries and arteries of erectile and secretory tissues. Neuropeptide Y is located in the same cardiovascular nerves as noradrenaline. It is depleted from the nerves by reserpine or 6-hydroxydopamine. Enkephalin nerves have been reported with small arteries in only a few vascular beds.

Animals

Substance P-containing nerves in the human small intestine. Distribution, ultrastructure, and characterization of the immunoreactive peptide.

Light and electron microscopic immunocytochemical techniques were used to examine the distribution and ultrastructure of substance P-immunoreactive nerves in human jejunum and distal ileum. The organization of human enteric substance P-containing nerves closely resembled that in other species. Dense arrays of varicose immunofluorescent fibers occurred in myenteric and submucous ganglia (which contained immunoreactive nerve cell bodies) and in the mucosa. There were fibers in both muscle layers, in the muscularis mucosae, and around blood vessels. Fibers in the myenteric plexus contributed to both ascending and descending pathways. Substance P-immunoreactive axon profiles contained small round and large round vesicles and were apposed to nerve cell bodies, and nonimmunoreactive and immunoreactive axon profiles. Synapselike contacts were occasionally observed on nerve cell bodies and processes. The substance P-like material was characterized by high pressure liquid chromatography and radioimmunoassay and found to be indistinguishable from the authentic undecapeptide. These results suggest that enteric nerves containing substance P may play similar roles in humans as in other species.

Adult

Plasma homovanillic acid and tardive dyskinesia during neuroleptic maintenance and withdrawal.

Plasma levels of homovanillic acid (HVA), a dopamine metabolite, were examined in 19 psychiatric inpatients during maintenance treatment on neuroleptic medications. A significant positive correlation was found between the level of HVA and the severity of tardive dyskinesia (TD) in these patients. Seven patients had their medication discontinued for 12 days. In spite of a fall in neuroleptic levels to negligible values, plasma HVA levels remained essentially stable while scores on the Abnormal Involuntary Movement Scale (AIMS) fell only slightly. The data support the hypothesis that some forms of TD may involve a persistent increase in presynaptic dopaminergic activity.

Adult

Phase contrast microscopy of microbial aggregates in the gingival sulcus of Macaca mulatta. Subgingival plaque bacteria in macaca mulatta.

The objective of this study was to study the relationship of microbial aggregates in the subgingival crevice to changes in periodontal health in Macaca mulatta. The sample included 68 oral sites from 17 Rhesus monkeys of various ages. The periodontal health of each site was evaluated using Plaque and Gingival Indices and crevice depth measurement. The subgingival plaque samples were examined by phase contrast microscopy and recorded on 16 mm film. A Microbial Index was developed based on a qualitative estimate of the numbers of organisms, morphology of predominant organisms, and the presence or absence of motility. The Microbial Index was demonstrated to be simple in use and highly reproducible. The findings indicate that changes in the Microbial Index are consistent with tissue changes seen in the periodontal status in M. mulatta. From this preliminary study, the oral flora of adult M. mulatta appears to have sufficient similarities to human oral flora to be used as a microbial model for experimental periodontal disease research. Future studies to refine and confirm the validity of the Microbial Index are warranted. It may prove to be a useful tool to monitor the effect of various treatment modalities on the periodontal flora and to determine the presence or absence of active disease.

Animals