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Biomedical subjects

R Murphy

Publications and source records attributed to R Murphy.

At least 127 records · Page 7Linked to original sources
PubMed1991

Comparison of the presence and actions of substance P and neurokinin A in guinea-pig taenia coli.

The presence and sites of action of two closely related tachykinins, substance P (SP) and neurokinin A (NKA), were examined in the taenia coli of the guinea-pig. SP- and NKA-like immunoreactivity (LI) were demonstrated histochemically in nerve fibres supplying the taenia. Chromatographic characterization of aqueous acetic acid extracts of taenia showed only one peak of SP-LI, corresponding in retention time to authentic SP, whereas there were multiple peaks of NKA-LI, the major one of which corresponded to authentic NKA. SP-LI and NKA-LI, determined by radioimmunoassay, were in a molar ratio of SP equivalents to NKA equivalents of 8.5:1 in taenia extracts. Extrinsic denervation of the caecum had no significant effect on the concentration of either SP-LI or NKA-LI or on their immunohistochemical distributions. Both SP and NKA (10(-10) to 10(-5) M) caused contractions of the taenia that were unaffected by hyoscine (10(-6) M), mepyramine (10(-6) M) or tetrodotoxin (5 x 10(-7) M), indicating that both peptides act directly on the smooth muscle of the taenia. Contractions to SP occurred after a short, but concentration-dependent, delay, reached a peak quickly, and then decayed. In contrast, NKA caused contractions after longer latencies, the peak was reached more slowly, and the response was maintained for up to 10 min. (D-Pro2, D-Trp7,9)-SP (10(-5) M) antagonised responses to SP and NKA to a similar degree. It is concluded that both NKA and SP should be considered as transmitter candidates for non-cholinergic nerve-mediated excitation in the taenia.

Animals↗
PubMed1991

Computer-assisted image analysis of skin surface replicas.

Using a rubber-based dental impression material, negative surface impressions were made of demarcated areas of skin and prepared as dry specimens for scanning-electron microscopy. Electron micrographs were taken at low magnification and, using a programmed computer-assisted image analyser, it was possible to represent quantitatively the topography of that particular body site according to the degree of circularity of the various geometric subunits. This technique was most applicable to skin topography with a reliable geometrical pattern of triangles and squares, a feature of hair-bearing surfaces in general and in particular, the antecubital fossa. Using standardized trauma of various types the origin of skin surface markings were found to be located in the dermis. The technique was applied to the healing of experimental trauma produced by tape stripping, the resolution of clinical eczema and a comparison of steroid-treated and untreated tape-stripped skin.

Eczema↗
PubMed1991

Epidemiologic patterns of upper respiratory illness and Pneumocystis carinii pneumonia in homosexual men.

The relationship between self-reported upper respiratory illness symptoms (URI) and human immunodeficiency virus Type 1 (HIV-1) was examined in homosexual men using semiannual visits from 1984 to 1988. Temporal and geographic patterns of Pneumocystis carinii pneumonia (PCP) diagnosis in these men during the same time period are also described. URI, including acute sinusitis, was reported more often by 916 HIV-1-seropositive participants than by 2,161 seronegative participants (32.21 versus 28.86% p less than 0.001). For 387 seropositive subjects who progressed to acquired immunodeficiency syndrome (AIDS), the proportion reporting URI peaked one visit pre-AIDS at a level significantly higher than matched control subjects (0.45 versus 0.28, p less than or equal to 0.001). The peak was higher for those with PCP as an initial diagnosis. Reported URI peaked in winter and troughed in summer, and PCP diagnosis rates peaked and troughed 4 months later, respectively. Cities with the highest reported rates of URI also had the highest proportions of AIDS cases with PCP as an initial diagnosis. No temporal or geographic patterns were observed for other HIV-1-related symptoms or non-PCP AIDS diagnoses. These patterns suggest the possibility of a person-to-person transmission of P. carinii similar to that of other respiratory pathogens, which would imply a need to consider stricter methods to prevent nosocomial transmission of this pathogen in inpatient and outpatient settings. Further investigation of these issues is needed.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Stimulation of astroglial 5-HT1A receptors releases the serotonergic growth factor, protein S-100, and alters astroglial morphology.

Stimulation of astroglial 5-HT1A receptors causes astroglial cells to acquire a more mature morphology and to release a factor (or factors) which promotes growth of serotonergic neurons. By using an antibody-blocking approach, we have shown that at least one of the growth-promoting factors thus released is the astroglial-specific protein S-100. This may be a particularly important observation, in view of studies implicating S-100 in both Down's syndrome and Alzheimer's disease.

Animals↗
PubMed1990

Isolation of HIV-1 from monocytes of individuals negative by conventional culture.

To improve isolation of human immunodeficiency virus (HIV) from purified monocytic cell populations, a differential culture technique was applied to blood from HIV-seropositive individuals, culture-negative for HIV by routine culture. When 206 individuals were grouped by percentage of CD4+ lymphocytes, increases in viral isolation rates were significantly associated with declines in percentage of CD4+ cells (P less than .0001). Of 158 asymptomatic individuals, 78% had greater than 400 CD4+ lymphocytes/mm3. Only 19% were culture-positive using routine methods. Separation of peripheral blood mononuclear cells (PBMC) into purified lymphocyte and monocyte subpopulations for 12 asymptomatic patients and subsequent HIV culture of each purified subpopulation using three different indicator cell lines resulted in 100% virus recovery from purified monocytes cultured in the U-937 promonocytic cell line. Culture of purified lymphocytes in U-937 cells did not increase the isolation rate, whereas culture of patient PBMC in U-937 indicator cells and in allogeneic monocytes resulted in a 50% increase in HIV isolation. A monocytic indicator cell line added to routine culture methods may improve virus recovery from asymptomatic individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Pharmacologic profile of a low molecular weight heparin (enoxaparin): experimental and clinical validation of the prophylactic antithrombotic effects.

Some 10 low molecular weight heparin products are currently available for commercial use. Enoxaparin and fraxiparin appear to be the most developed low molecular weight heparins. Many well-designed clinical trials have been carried out for different clinical indications with both of these products. As shown in both experimental and clinical settings, the prophylactic antithrombotic efficacy of enoxaparin is distinct from other low molecular weight heparins. Enoxaparin has provided consistently impressive clinical results. Moreover, at comparable dosages, other products have exhibited safety/efficacy profiles different from that of enoxaparin. The clinical performance of each low molecular weight heparin is characteristic of only that particular agent. Besides the commercially available low molecular weight heparin preparations, some 14 other agents are under development at this time. Although each product has similar basic characteristics, their biological actions should be studied carefully. Apart from differences in the physicochemical properties, the pharmacologic actions of these agents may differ significantly. Only results from valid clinical trials will show similarities or differences between the low molecular weight heparins. Other manufacturers should follow the lead of enoxaparin and conduct their own clinical trials on each of their products.

Animals↗
PubMed1989

Analogues of vasoactive intestinal peptide (VIP) contract the guinea-pig uterine artery but do not antagonize VIP-induced relaxations.

Guinea-pig vasoactive intestinal peptide (gpVIP-(1-28] in the concentration range 3 x 10(-9)-3 x 10(-7) mol.1-1 relaxed precontracted segments of the guinea-pig uterine artery. Porcine VIP-(10-28) (pVIP-(10-28], [4-Cl-D-Phe6,Leu17]VIP, or [N-Ac-Tyr1, D-Phe2]GRF-(1-29)-NH2 did not antagonize VIP-induced relaxations of the artery, but high concentrations of the two VIP analogues produced large, transient contractions of the artery. In some preparations 10(-5) mol.1-1 gpVIP-(1-28) also caused transient arterial contractions. These data indicate the presence of two distinct receptors for VIP on the guinea-pig uterine artery, mediating opposite effects on vascular tone.

Animals↗
PubMed1989

Projections of neurons with neuromedin U-like immunoreactivity in the small intestine of the guinea-pig.

Neuromedin U immunoreactivity was located histochemically in the guinea-pig small intestine. Projections of immunoreactive neurons were determined by analysing patterns of degeneration following nerve lesions. The co-localization of neuromedin U immunoreactivity with immunoreactivity for substance P, neuropeptide Y, vasoactive intestinal peptide and calbindin was also investigated. Neuromedin U immunoreactivity was found in nerve cells in the myenteric and submucous plexuses and in nerve fibres in these ganglionated plexuses, around submucous arterioles and in the mucosa. Reactive fibres did not supply the muscle layers. Most reactive nerve cells in the myenteric ganglia had Dogiel type-II morphology and in many there was co-localization of calbindin, although some Dogiel type-II neuromedin U neurons were calbindin negative. Lesion studies suggest that these myenteric neurons project circumferentially to local myenteric ganglia. Projections from myenteric neurons also run anally in the myenteric plexus, while other projections extend to submucous ganglia, and still further projections run from the intestine to provide terminals in the coeliac ganglia. In the submucous ganglia neuromedin U was co-localized in three populations of nerve cells: (i) those with vasoactive intestinal peptide immunoreactivity, (ii) neurons containing neuropeptide Y, and (iii) neurons containing substance P. Each of these populations sends nerve fibres to the mucosa. Neuromedin U immunoreactivity is thus located in a variety of neurons serving different functions in the intestine and therefore probably does not have a single role in intestinal physiology.

Animals↗
PubMed1989

Measurement and chromatographic characterization of prodynorphin-derived peptides in the guinea-pig ileum.

Guinea-pig ileum was dissected and the mucosa, submucosa and external musculature extracted with aqueous acetic acid for measurement of four prodynorphin-derived peptides, namely dynorphin A 1-8, dynorphin A 1-17, dynorphin B, and alpha-neoendorphin. The peptide-like immunoreactive material extracted from the external musculature was characterized by multi-dimensional chromatographic analysis and compared to synthetic porcine standards. The chromatographic methods utilized were: reversed-phase high performance liquid chromatography (RP-HPLC), using two different eluants; cation exchange high performance liquid chromatography (CE-HPLC) and gel filtration chromatography. The dynorphin A 1-8-like immunoreactive material was homogeneous and coeluted with the standard in all chromatographic modes. The dynorphin A 1-17-like and dynorphin B-like immunoreactive material was heterogeneous but showed a peak that coeluted with synthetic standard in all chromatographic modes. The alpha-neoendorphin-like immunoreactive material also appeared to be heterogeneous with the major component on CE-HPLC coeluting with the synthetic peptide standard while the major component on RP-HPLC eluted differently. It was concluded that the guinea-pig ileum contains immunoreactivity for peptides derived from all coding regions of the prodynorphin gene and that these peptides may be present in multiple immunoreactive forms.

Animals↗
PubMed1989

Correlated functional and structural analysis of enteric neural circuits.

Views about the roles and nature of the enteric nervous system have changed dramatically in the last ten years. This system of neurons is recognized to control, through reflex pathways intrinsic to the gut wall, motility, transport of water and electrolytes, and blood flow in the small and large intestines. There are thus a range of neuron types in the enteric nervous system, including sensory neurons, motor neurons, and interneurons, involved in the control of each of these functions. The present paper deals with the recent efforts to provide an integrated functional and structural description of the nerve circuits. One of the challenges in this quest has been to identify primary sensory neurons and final motor neurons involved in motility control. Evidence is presented that in the guinea-pig small intestine the primary sensory neurons have Dogiel type II morphology and are, electrophysiologically, AH neurons. They send circumferential processes to adjacent myenteric ganglia and some of them, at least, have processes leading from the mucosa. Motor neurons are S neurons, with cell bodies in the myenteric plexus. Those that supply the circular muscle are Dogiel type I neurons and provide processes that run circumferentially for about one third of the circumference of the intestine. The circuits for secretomotor reflexes have been partly worked out. The secretomotor neurons have cell bodies in the submucous ganglia and are activated to return water and electrolytes to the lumen during digestion. The secretomotor reflexes are regulated, in accord with whole body water and electrolyte homeostasis, via sympathetic neurons which lower the excitability of secretomotor neurons.

Animals↗
PubMed1989

Campylobacter pylori in patients with dyspeptic symptoms and endoscopic evidence of erosion(s).

The relationship between Campylobacter pylori (CP), histologic gastritis, and dyspeptic symptoms is becoming gradually clearer, but there is still a lack of knowledge of the natural history of treated or untreated gastritis. We examined serial biopsies from the gastric fundus, body, and antrum, and from the duodenum in 16 dyspeptic patients. Patients with concomitant peptic ulcers, alcoholism, or nonsteroidal anti-inflammatory drug use were excluded. CP was present in the biopsies of 50% of patients at presentation. When CP was present, the antrum was always infected, and often had the highest density of organisms. In the duodenum, CP was found only in areas of gastric metaplasia. The presence of CP was highly correlated with gastritis activity (neutrophilic infiltrate). A 4-yr follow-up study of symptoms, endoscopic appearance, and histologic findings including the presence of CP was performed in 10 of the original 16 patients. After 4 yr, both the severity and frequency of epigastric pain remained the same in seven patients, worsened in one, and improved in two. All patients who had CP at initial presentation retained the organism (5/10), whereas none of the previously noninfected patients acquired the infection (5/10). Both CP-positive and -negative patients were treated for 3 wk with 524 mg bismuth subsalicylate qid, and for the first 2 of 3 wk with 250 mg metronidazole qid. One patient who was CP positive was lost to follow-up. In three of the remaining four patients on this regimen, the organism was eradicated. Of the nine patients who completed the treatment program, two had no change in symptoms and seven improved. CP was present in three of seven with improved symptoms and in one of two with no change in symptoms. After treatment, the only change in histology was the disappearance of activity in the CP-positive patients who lost the organism. In conclusion, CP was present in 50% of dyspeptic patients with endoscopic evidence of at least one erosion. Both the symptoms and CP persisted for 4 yr. Dyspeptic symptoms improved after bismuth subsalicylate/metronidazole therapy, regardless of the presence or absence of CP, although the regimen did succeed in eradicating the organism in three of the four CP-positive patients who completed the study.

Adolescent↗