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Biomedical subjects

J W Lewis

Publications and source records attributed to J W Lewis.

At least 127 records · Page 7Linked to original sources
PubMed1996

Methoclocinnamox: agonist and antagonist effects of a novel long-lasting opioid in rhesus monkeys.

The present studies characterized the agonist and antagonist effects of methoclocinnamox, a novel codeinone, in the warm-water (50 degrees C and 55 degrees C) tail-withdrawal assay of thermal antinociception in rhesus monkeys. Methoclocinnamox (0.1-1.0 mg/ kg) was fully effective in the warm-water tail-withdrawal assay in 50 degrees C but not 55 degrees C water, similar to previously studied mu-opioid partial agonists. Consistent with this, methoclocinnamox (0.32 mg/kg), at a time when it acted as an agonist in 50 degrees C water, was an antagonist of the higher efficacy mu-agonist fentanyl in 55 degrees C water. The agonist effects of methoclocinnamox were antagonized by quadazocine (1.0 mg/kg), but to a lesser degree than would be expected for competitive antagonism at mu-receptors. However, the nonequilibrium mu-selective antagonist clocinnamox (0.32 mg/kg) completely blocked the antinociceptive effect of methoclocinnamox. After its agonist effects had waned (typically < 24 hr), methoclocinnamox (0.1-1.0 mg/ kg) caused long-lasting and nonparallel shifts in the dose-effect curves of the mu-agonist morphine, whereas even at the highest dose (1.0 mg/kg) methoclocinnamox did not antagonize the kappa-agonist U50,488. It is concluded that methoclocinnamox exhibits initial opioid agonist effects, followed by prolonged, insurmountable, mu-antagonist effects.

Analgesics, Opioid↗
PubMed1995

Two rules for callosal connectivity in striate cortex of the rat.

In the rat, callosal cells occupy lateral as well as medial portions of striate cortex. In the region of the border between areas 17 and 18, which contains a representation of the vertical meridian of the visual field, cells projecting through the corpus callosum are concentrated throughout the depth of the cortex. In contrast, in medial portion of striate cortex, where peripheral portions of the visual field are represented, callosal cells are preferentially found in infragranular layers. These differences in topography and laminar distribution suggest that these callosal regions, referred to as medial and lateral callosal regions in the present study, subserve different functions. We explored this possibility by analyzing the patterns of callosal linkages in these two callosal regions. We charted the location of retrogradely labeled cells within striate cortex of one hemisphere after placing restricted injections of one or more fluorescent tracers into selected sites in the contralateral striate cortex. We found the medial and lateral callosal regions have distinctly different topographic organizations. Injections into medial striate cortex of one hemisphere produced labeled cells predominantly in mirror-symmetric loci in medial portions of contralateral striate cortex. The arrangement of these connections suggests that they mediate direct interactions between cortical regions representing visual fields located symmetrically on opposite sides of the vertical meridian of the visual field. In contrast, the mapping in the lateral callosal region is reversed: injections into the 17/18a border produced labeled fields located medial to the contralateral 17/18a border, while injections slightly medial to the 17/18a border produced labeled fields located at the contralateral 17/18a border.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Chloride effect on the early photolysis intermediates of a gecko cone-type visual pigment.

Nanosecond laser photolysis measurements were conducted on the cone-type visual pigment P521 in digitonin extracts of Tokay gecko (Gekko gekko) retina containing physiological chloride ion levels and also on samples which had been chloride depleted or which contained high levels (4 M) of chloride. Absorbance difference spectra were recorded at a sequence of time delays from 30 ns to 60 microseconds following excitation with a pulse of either 532- or 477-nm actinic light. Global analysis showed the kinetic decay data for gecko pigment P521 to be best fit by two exponential processes under all chloride conditions. The initial photoproduct detected had a broad spectrum characteristic of an equilibrated mixture of a Batho P521 intermediate with its blue-shifted intermediate (BSI P521) decay product. The first exponential process was assigned to the decay of this mixture to the Lumi P521 intermediate. The second exponential process was identified as the decay of Lumi P521 to Meta I P521. The initial photoproduct's spectrum exhibited a strong dependence on chloride concentration, indicating that chloride affects the composition of the equilibrated mixture of Batho P521 and BSI P521. These results suggest that the affinity for chloride is reduced approximately 5-fold in the Batho P521 intermediate and approximately 50-fold in the BSI P521 intermediate. Chloride concentration also affects the apparent decay rate of the equilibrated mixture. When the apparent decay rate is corrected for the composition of the equilibrated mixture, a relatively invariant microscopic rate constant is obtained for BSI decay (k = 1/55 ns-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Receptor reserve and affinity of mu opioid agonists in mouse antinociception: correlation with receptor binding.

In order to quantitate the extent to which opioid agonist potencies obtained in behavioral assays are determined by the apparent in vivo affinity and efficacy of the agonist, the antinociceptive effects of the mu opioid agonists morphine, fentanyl, etonitazene, and NIH 10741 were assessed before and after administration of the insurmountable mu opioid antagonist clocinnamox (CCAM) in a 55 degrees C warm-water tail withdrawal test in Swiss albino mice. Under control conditions, all four mu opioid agonists produced a full antinociceptive response with the following ED50 values (in mg/kg): morphine, 12; fentanyl, 0.47; etonitazene, 0.039; NIH 10741, 0.0051. Analysis of CCAM's effects according to Black and Leff gave the following agonist efficacy or tau values: Morphine, 4; fentanyl 15, etonitazene, 7; and NIH 10741, 59. The respective KA values were (in mg/kg): morphine, 29; fentanyl, 7.3; etonitazene, 0.22; and NIH 10741, 0.30. The major determinant of the experimentally observed ED50 values seemed to be the apparent in vivo affinity of the respective agonist and not its efficacy. KA values (expressed as mol/kg) correlated with the Ki values (in mol/l) obtained with [3H]DAMGO radioligand binding (r = 0.96 for pKA vs. pKi), although being on average 11,000-fold higher. Values for q, the available receptor fraction as determined in the behavioral experiments, correlated strongly (r = 0.96) with the q values determined by ex vivo [3H]DAMGO- and [3H]naltrexone equilibrium binding (i.e., Bmax,clocinnamox/Bmax,control), the relationship approaching unity.

Analgesia↗
PubMed1995

Epidemiological studies on intestinal helminth parasites of rural and urban red foxes (Vulpes vulpes) in the United Kingdom.

An epidemiological study of intestinal helminths in 843 foxes (Vulpes vulpes) from southern England revealed the presence of 13 parasite species: five nematodes--Toxocara canis (prevalence 55.9%), Toxascaris leonina (1.5%), Uncinaria stenocephala (68.0%), Trichuris vulpis (0.5%) and Capillaria aerophila (0.2%); four cestodes--Taenia pisiformis (13.8%), Taenia hydatigena (2.5%), Echinococcus granulosus (0.1%) and Dipylidium caninum (3.8%); two trematodes--Brachylaima recurva (2.9%) and Cryptocotyle lingua (2.3%); two acanthocephalans--Prosthorhynchus transversus (0.7%) and Macracanthorhynchus catulinus (0.1%). Trichuris vulpis, Brachylaima recurva, Macracanthorhynchus catulinus and Prosthorhynchus transversus are new host records for the UK. Results are discussed with reference to variations in the diets of urban and rural foxes and to their potential as reservoir hosts for helminths of medical and veterinary importance.

Animals↗
PubMed1995

Low-temperature trapping of early photointermediates of alpha-isorhodopsin.

Alpha-Isorhodopsin, an artificial visual pigment with a 9-cis-4,5-dehydro-5,6-dihydro(alpha)retinal chromophore, was photolyzed at low temperatures and absorption difference spectra were collected as the sample was warmed. A bathorhodopsin (Batho)-like intermediate absorbing at ca 495 nm was detected below 55 K,a blue-shifted intermediate (BSI)-like intermediate absorbing at ca 453 nm was observed when the temperature was raised to 60 K and a lumirhodopsin (Lumi)-like intermediate absorbing at ca 470 nm was found when the sample was warmed to 115 K. Photointermediates from this pigment were compared to those of native rhodopsin and 5,6-dihydroisorhodopsin. As in native rhodopsin, Batho is the first intermediate detected in alpha-isorhodopsin, though unlike native rhodopsin at low temperatures BSI is observed prior to Lumi formation. Alpha-Isohodopsin behaves similarly to 5,6-dihydroisorhodopsin, with the same early intermediates observed in both artificial visual pigments lacking the C5-C6 double bond. The transition temperature for BSI formation is higher in alpha-isorhodopsin, suggesting an interaction involving the chromophore ring in BSI formation. The transition temperature for Lumi formation is similar for these two pigments as well as for native rhodopsin, suggesting comparable changes in the protein environment in that transition.

Cold Temperature↗
PubMed1994

Metabolic labelling of wild and laboratory subspecies of the trichostrongyle nematode Heligmosomoides polygyrus.

The immunological, biochemical and taxonomic relationship between wild and laboratory subspecies of Heligmosomoides polygyrus was studied by metabolically labelling parasite proteins with [35S]-methionine. Much variability, both in content and synthesis of proteins was observed between the two subspecies. Laboratory female worms had a higher protein content and incorporated more radioactive label into somatic proteins than their wild counterparts. Incorporation of radioactivity into excretory/secretory (ES) proteins, predicted to contain important antigens, demonstrates a major reduction in synthesis of proteins with molecular weights 66, 55, 43, 41, 40, 39, 37, 28 and 16 kDa by laboratory females. These differences in protein synthesis might explain the differing infectivities of the two subspecies when passaged in inbred laboratory (Mus musculus) and wild (Apodemus sylvaticus) mice.

Animals↗
PubMed1994

The distribution and host range of species of the blood fluke Sanguinicola in British freshwater fish.

The distribution of host range of Sanguinicola armata, S. inermis and S. volgensis in British freshwater fish are described. S. inermis has been recorded in carp Cyprinus carpio, crucian carp Carassius carassius and tench Tinca tinca in southern, central and eastern England and in koi carp imported from Japan. S. armata has been detected in pike Esox lucius and tench and S. volgensis has been found in chub Leuciscus cephalus, dace Leuciscus leuciscus, perch Perca fluviatilis, roach Rutilus rutilus and pike in southern and eastern England. The first record of the co-occurrence of two species of Sanguinicola (S. inermis and S. volgensis) in a British inland water is reported. The importance of blood flukes and the role of anthropochore movement of fish hosts in dissemination of S. inermis are discussed.

Animals↗
PubMed1994

Genomic variability within laboratory and wild subspecies of Heligmosomoides polygyrus.

Genomic DNA extracted from laboratory and wild subspecies of the trichostrongyle nematode Heligmosomoides polygyrus were compared using RFLP and DNA/DNA hybridization techniques. Eight restriction endonuclease digests of the genomic DNA of the two subspecies were hybridized with heterologous ribosomal DNA probes and the total radio-isotope labelled DNA of the laboratory subspecies. DNA hybridization of the two subspecies of H. polygyrus yielded different banding patterns when probed with the rDNA clones in Pvu II digests and when total genomic DNA was used as the probe in Hind III and Pvu II digests. The remaining hybridization profiles of both subspecies were identical.

Animals↗
PubMed1994

Ultrastructure of the digestive system of adult Sanguinicola inermis.

The alimentary tract of adult Sanguinicola inermis Plehn, 1905 (Digenea: Sanguinicolidae) was studied by transmission electron microscopy. A highly developed muscular region, likely to be a modified sucker, is present anteriorly to the oesophagus. The tegumental oesophagus, on the basis of the characteristics of the surface cytoplasm, is differentiated into anterior, median and posterior regions with the apical cytoplasm of the median oesophagus drawn into extracellular vesicles from which arise surface knobs. The oesophagus leads to a cellular intestine composed of a single layer of epithelial cells. The apical surface of the intestine is drawn into short luminal projections and the intestinal cells contain numerous organelles and secretory granules. No host cells or cell debris were evident within the alimentary tract, although the intestinal lumen was filled with electron-dense material.

Animals↗
PubMed1994

The morphology of hymenolepidid and dilepidid cestodes from common and pygmy shrews (Soricidae) in southeast England.

One hundred and six of 109 common shrews (Sorex araneus) and 62 of 72 pygmy shrews (S. minutus), obtained by Longworth trapping in Southeast England, were infected with cestodes. Ten species were recovered: Choanotaenia hepatica and Hymenolepis prolifer (found in S. araneus); Choanotaenia crassiscolex, Hymenolepis furcata, H. jacutensis, H. schaldybini, H. scutigera, H. singularis, H. diaphana and H. infirma (in both hosts). The morphology, taxonomy and ecology of these species are discussed and the findings of the present study are discussed with reference to previous studies of the helminth fauna of British shrews. Cysticercoids of C. crassiscolex were found in the snail, Vitrina pellucida, and cysticercoids of H. schaldybini in the staphylinid beetle, Anthobium unicolor.

Animals↗
PubMed1994

Two new species of Eumegacetes Looss, 1900 (Digenea: Eumegacetidae) from Egyptian birds.

Two new species of the genus Eumegacetes Looss, 1900 are described from avian hosts in Sharkia province, Egypt and these include Eumegacetes (Anterovitellum) pycnonotus n. sp. from the bulbul, Pycnonotus barbatus, and E. (Posthovitellum) hirundus n. sp. from the barn swallow Hirundo rustica saviginii. The descriptions are based primarily on differences in the shape and elevation of the intestinal caeca, the position of the genital opening and the shape and distribution of the vitelline follicles, testes, ovary and uterine loops.

Animals↗
PubMed1994

Irreversible opioid antagonist effects of clocinnamox on opioid analgesia and mu receptor binding in mice.

The effects of the systemically active irreversible opioid receptor antagonist clocinnamox (C-CAM; 14 beta-(p-chlorocinnamoylamino)-7,8-dihydro-N- cyclopropylmethyl normorphinone mesylate) on mu receptor binding to cerebral membranes and on mu opioid analgesia were assessed using mice. After systemic administration, C-CAM produced a dose-dependent decrease in the Bmax values of both [3H]DAMGO ([D-Ala2, N-MePhe4, Gly5-ol][tyrosyl-3,5-3H]enkephalin) and [3H]naltrexone without affecting the Kd value of either ligand. After administration of 3.2 mg/kg of C-CAM, [3H]DAMGO binding recovered gradually, returning to control levels by 8 days. This time course of recovery was similar to that observed with 3.2 mg/kg of C-CAM against morphine analgesia in the warm-water tail-withdrawal assay. The analgesic effect of the mu agonist etonitazene also was assessed in the assay. C-CAM produced dose-dependent rightward and slight downward shifts of the etonitazene dose-effect curve. The analgesic activity of etonitazene had still not returned to base-line levels 12 days after administration of 32 mg/kg of C-CAM, a time at which [3H]DAMGO binding had returned to control levels. In addition, the apparent pA2 values of etonitazene with naltrexone in the tail-withdrawal assay were assessed at 4, 8 and 12 days after the administration of 32 mg/kg of C-CAM, and none were found to be different from the control pA2 value. These results support the notion that C-CAM is an irreversible mu receptor antagonist and suggest that post-treatment, perhaps newly synthesized, mu receptors are similar to mu receptors in control membranes.

Analgesia↗
PubMed1994

Right heart function and prediction of respiratory morbidity in patients undergoing pneumonectomy with moderately severe cardiopulmonary dysfunction.

Detailed hemodynamic monitoring was performed in 20 patients undergoing pneumonectomy with moderately severe chronic obstructive pulmonary disease. Flow-directed pulmonary artery catheters capable of determining thermal dilution right ventricular ejection fraction and other indexes of right ventricular performance were placed in each patient. The mean actual and percent values for forced expiratory volume in 1 second in this group were 1.8 +/- 0.5 L and 66% +/- 18%, respectively. Pulmonary hypertension was present in 76.5% of patients at the baseline nonintubated state. At pulmonary artery clamping, 53.8% of this subgroup had no change or a mean drop of 8 mm Hg in pressure. The remaining had a mean rise of 12 mm Hg. Mean systolic pulmonary artery pressures in this subset (41 mm Hg) did not change from the nonintubated state to pulmonary artery clamping. Patients with normal pulmonary artery pressures before intubation had an average rise of only 4 mm Hg at pulmonary artery clamping. In the immediate postoperative period, only 10.0% of the entire group had normal pulmonary artery pressures. Right ventricular ejection fraction and pulmonary vascular resistance were normal in 58.8% and 94.1%, respectively, at the baseline nonintubated state. Abnormal right ventricular ejection fraction values (< 45%) were present in 70.0% of patients at pulmonary artery clamping; 25.0% fell below 35%. Pulmonary vascular resistance increased above 200 dyne.sec.cm-5 in 30.0% at pulmonary artery clamping. No correlation was found between right ventricular ejection fraction and pulmonary vascular resistance or pulmonary artery pressure during operation. No pulmonary function test or hemodynamic variable measured in this study accurately predicted the days of hospital stay or early postoperative cardiopulmonary morbidity. At the baseline nonintubated state, no parameter consistently predicted late New York Heart Association class III/IV. At the time of pulmonary artery clamping, a right ventricular ejection fraction of less than 35%, a pulmonary vascular resistance greater than or equal to 200 dyne.sec.cm-5, and a pulmonary vascular resistance/right ventricular ejection fraction ratio greater than or equal to 5.0 predicted the development of long-term cardiopulmonary disability. Thirteen patients (65.0%) in this series with abnormally low preoperative pulmonary function could have been excluded from pneumonectomy. Only five of 13 patients (38.5%) had late class III/IV symptoms. Four of these five patients had a right ventricular ejection fraction less than 35% during operation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

In vivo determination of mu opioid receptor turnover in rhesus monkeys after irreversible blockade with clocinnamox.

In a warm-water tail withdrawal antinociception assay performed at 45, 50 and 55 degrees C in the rhesus monkey, the irreversible opioid antagonist clocinnamox at a dose of 0.1 mg/kg s.c. produced an acute rightward shift of the dose-response curves of the selective mu opioid agonists alfentanil and morphine at all tested temperatures. In addition, clocinnamox depressed the maxima of the dose-response curves for both agonists at 50 and 55 degrees C. Analysis of these data according to Furchgott as modified by Black and Leff showed that clocinnamox acutely decreased mu opioid receptors available for alfentanil by 88%; receptor numbers returned to control levels with a half-life of 6.3 days. Assessment of receptor population changes after clocinnamox administration with either alfentanil or morphine gave essentially identical results: 2 to 4 weeks after clocinnamox, the receptor population not only returned to preclocinnamox levels, but actually showed an overshoot. In contrast, apparent values of alfentanil affinity; its efficacy, e; the theoretically obtainable maximum effect of the mu opioid antinociceptive system, Em; and the stimulus-response transducing factor, n; did not change significantly over time. Alfentanil showed a 29-fold higher affinity than morphine, the respective KA values being 0.84 mg/kg for alfentanil and 24 mg/kg for morphine. The efficacy of alfentanil was always 2- to 3-fold higher than that of morphine for any temperature tested, the efficacies of both mu opioid agonists being higher at lower temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)

Alfentanil↗
PubMed1993

Effects of temperature on rhodopsin photointermediates from lumirhodopsin to metarhodopsin II.

Absorbance changes following the photolysis of mildly sonicated membrane suspensions of bovine rhodopsin are monitored using multichannel detection at 15, 20, 25, 30, and 35 degrees C. Difference spectra collected with microsecond time resolution are analyzed by singular value decomposition and multiexponential fitting. Several kinetic schemes are tested using methods that compare the observed rates and associated spectral amplitudes to the eigenvalues and eigenvectors of kinetic matrices. The time evolution of the spectra is more complex than can be accounted for by the traditional lumi-->metarhodopsin I<-->metarhodopsin II scheme. Above 25 degrees C, the formation of metarhodopsin II is achieved without a large transient accumulation of metarhodopsin I. Within the framework of first-order kinetics, the observations are explained by simple kinetic schemes that lead to the formation of a deprotonated Schiff's base species temporally distinct from metarhodopsin II directly upon the decay of lumirhodopsin.

Kinetics↗