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Biomedical subjects

R Murphy

Publications and source records attributed to R Murphy.

At least 163 records · Page 9Linked to original sources

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↗

Health education: perspective for PAs.

Health Education is a valid part of the PA's armamentarium which should be developed to maintain pace with the continuing role evolution of PAs. The Health Belief Model is useful as a means of understanding how patients are motivated to accept health-promoting behavioral and life-style changes. The PA, according to his or her own unique interests, experience, and ingenuity, must develop plans and methods for implementation of specific interventions, but the five priority actions delineated by the Surgeon General can serve as a basis. These include the areas of smoking cessation, alcohol and drug management, nutritional guidance, and the management of psychosocial stress. The authors provide a table of references in these areas.

Health Education↗

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↗

Partial resolution of tardive dyskinesia with treatment of co-existing thyrotoxicosis.

Neuroleptic-induced tardive dyskinesia improved after treatment of thyrotoxicosis. Neuroleptic blood levels indicated that the improvement was not caused by masking of the symptoms by rising drug levels. Dopamine metabolite measurements suggested that the thyrotoxicosis caused an increase in the sensitivity of caudate neurons to dopamine, rather than a change in release of dopamine.

Dopamine↗

Physiochemical studies on indocyanine green: molar lineic absorbance, pH tolerance, activation energy and rate of decay in various solvents.

Physiochemical studies were carried out on the tricarbocyanine dye indocyanine green in biological fluids and organic solvents. The molar lineic absorbance epsilon of the compound was highest in organic solvents (methanol, 1.2-propanediol, dimethylformamide) and bile, but lowest in water and duodenal fluid. Indocyanine green remained stable in methanol and bile (t1/2 greater than 1 year) but was rapidly decomposed to a colourless derivative in duodenal fluid and distilled water (t1/2 3.6 days and 1.4 days, respectively). It was thermostable (120 degrees C) in methanol and 1.2-propanediol but thermolabile in water and dimethylformamide where the activation energy for the decomposition reaction was low. At ambient temperature (20 degrees C) indocyanine green was particularly labile at pH less than 5 and pH greater than 11. The rate of decay of indocyanine green in various solvents indicated that the rate limiting step in the decay process was either a first or zero order reaction.

Chemical Phenomena↗

Physiochemical studies of indocyanine green (ICG): absorbance/concentration relationship, pH tolerance and assay precision in various solvents.

Indocyanine green (ICG) obeyed the Beer-Lambert law within the concentration range 1.25 micrograms/ml-10.0 micrograms/ml in distilled water, methanol, dimethylformamide (DMF), 1.2-propanediol and aqueous buffers (pH 9.0), but only up to 7.5 micrograms/ml in human bile and 0.5% human albumin, and only to 5.0 micrograms/ml in human duodenal fluid. ICG was rapidly (less than 1 h) decomposed to a colorless derivative at pH less than 5 and greater than 11, but remained relatively stable for 48 h at pH 8-10. ICG is an indicator and a weak acid with a pKa of 3.27. In bile stabilized with 25% methanol, the precision of the method (CV) is 5% and the accuracy is 106-127%.

Bile↗

Baroreceptor reflexes in conscious guinea-pigs are unaffected by depletion of cardiovascular substance P nerves.

Adult guinea-pigs were injected with doses of capsaicin increasing from 10 mg/kg to 400 mg/kg over 6-days. The guinea-pigs were supplied with indwelling arterial cannulae 14 days later and the next day cardiovascular function was assessed in the conscious animals. Resting blood pressures and heart rates were recorded and then baroreceptor reflex function was evaluated by recording the changes in heart period which were evoked by blood pressure responses to injections of phenylephrine and glyceryl trinitrate. Substance P was measured by radioimmunoassay and its localization examined by immunohistochemistry. The capsaicin treatment caused a substantial reduction in substance P levels in vascular and cardiac nerves. However, there were no changes in resting heart rate, blood pressure or baroreceptor sensitivity. It is concluded that the widespread substance P nerves associated with the heart and blood vessels are not necessary for baroreceptor reflex function. Their role or roles remain unknown.

Animals↗

Substance P in nerve tissue in the gut.

Substance P is present in intrinsic nerves in the intestine and in some extrinsic sensory nerves. It can be released from these nerves to act on the muscle layers and on other enteric neurons. Immunohistochemical studies show that the enteric substance P neurons are short and branch profusely to supply all intestinal layers. Pharmacological studies indicate that enteric substance P neurons receive inputs from enteric cholinergic interneurons. This suggests that these neurons are part of multineuronal nerve pathways in the intestine. The substance P neurons are not essential for the enteric reflexes which subserve peristalsis but they appear to modulate these reflexes.

Acetylcholine↗

Pharmacological inhibition of chenodeoxycholate-induced fluid and mucus secretion and mucosal injury in the rabbit colon.

The effects of various pharmacological agents on bile acid-induced fluid secretion, mucus secretion, and mucosal injury were investigated using a perfusion technique in rabbit colon. Atropine markedly reduced and carbachol potentiated the fluid secretion, mucus output, and mucosal damage observed during bile acid perfusion. In contrast, pretreatment of the colonic mucosa with lignocaine and parenteral administration of methysergide and somatostatin produced a modest reduction in the fluid secretory response without apparent effects on mucus output or mucosal damage. These results suggested that cholinergic agonists and antagonists influence the mucosal resistance to bile acid-induced injury possibly through their effects on mucus secretion. Increasing or decreasing mucosal resistance to the detergent effects of bile acids appeared to have marked effects on the magnitude of induced fluid secretion. A minor reduction in overall secretory response to bile acids was also apparent with agents not influencing mucus secretion or mucosal injury.

Animals↗

Characterization of substance P-like immunoreactivity in peripheral sensory nerves and enteric nerves by high pressure liquid chromatography and radioimmunoassay.

Material exhibiting immunoreactivity for substance P in enteric nerves, obtained from the myenteric plexus of the guinea pig small intestine, and in the peripheral ends of sensory nerves of the ureter, atrium and superior mesenteric artery, was characterized by separation by high pressure liquid chromatography, and quantified by radioimmunoassay of fractions collected from the chromatograph. Capsaicin, which depletes substance P-like immunoreactivity from sensory, but not from other substance P-containing nerves, reduced the content of substance P-like immunoreactivity in ureter, atrium and superior mesenteric artery by more than 99.5%, whereas the reduction in immunoreactive material in the myenteric plexus was less than 10%. Separation of extracts of myenteric plexus, ureter and atrium on a reversed-phase column gave major peaks corresponding to authentic substance P and minor peaks that coeluted with oxidized substance P. If the extracts were oxidized with hydrogen peroxide before chromatography, all the immunoreactivity was found in the peak corresponding to oxidized substance P. In the superior mesenteric artery extracts, in addition to the components corresponding to substance P and its oxidized derivative, there was a small intermediate peak that has yet to be identified. Physalaemin, which has been suggested to be present in mammalian nerves, was not detectable in any of the extracts. It is concluded that both enteric nerves and the peripheral processes of sensory nerves which show immunoreactivity for substance P in this species contain the authentic peptide.

Animals↗

Somatostatin is contained in and released from cholinergic nerves in the heart of the toad Bufo marinus.

The heart of the toad Bufo marinus contained a substance with somatostatin-like immunoreactivity which eluted with somatostatin on reverse phase high pressure liquid chromatography. Immunoreactivity to somatostatin was localised histochemically to nerve fibers in muscle bundles of the sinus venosus, atria and ventricles and to nerve cell bodies in the sinus venosus and inter-atrial septum. Nerve cell bodies were localised both by interference contrast microscopy and immunohistochemistry; all detectable intracardiac neurons were immunoreactive. Synthetic somatostatin inhibited the rate and force of beat of atrial preparations, but did not affect the driven ventricle. Vagal stimulation caused inhibition of all cardiac chambers. After muscarinic blockade with hyoscine, vagal stimulation with 3 Hz or more still caused inhibition of the pacemaker and atrium, but not of the ventricle. The hyoscine-resistant vagal effects were diminished by about 60% after induction of tachyphylaxis to somatostatin. When when the vagus nerves were stimulated intermittently for 1 h at 10 Hz, in the presence or absence of hyoscine, the effect of somatostatin was reduced by about 60%. It is concluded that the cholinergic postganglionic neurons of the cardiac vagus contain somatostatin. When the vagus is stimulated at 3 Hz or more, the neurons release sufficient somatostatin to inhibit the pacemaker and atrial muscle.

Animals↗