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Biomedical subjects

J W Lewis

Publications and source records attributed to J W Lewis.

At least 55 records · Page 3Linked to original sources

Pathological and physiological changes in the South African freshwater crab Potamonautes warreni calman induced by microbial gill infestations.

The impact of microbial gill infestations on the pathology and physiology of the freshwater crab Potamonautes warreni was investigated by comparison of infested and uninfested crab populations from, respectively, a polluted and an unpolluted site along the Mooi River, North West Province, South Africa. Heavy gill infestations by bacteria (70%), peritrichous ciliates such as Lagenophrys sp. (15%), Zoothamnium sp. (10%), and Epistylis sp. (5%), and motile protozoans resulted in species-specific lesions in the gill epithelia of P. warreni and physiological changes in crabs from the polluted site. Bacterial colonies enmeshed in polysaccharide-like films produced indentations of the gill cuticular surfaces and dissociation of microvillous membranes at the basal zone of epithelial cells of gill lamellae of P. warreni. Lagenophrys sp. induced large subcuticular spaces with an unfolding or resorption of the plasma membrane in the gill epithelia. The attachment of stalks of Zoothamnium and Epistylis resulted in dilation of lamellar tissues, the formation of vacuoles, and an increase in subcuticular spaces in the epithelia. Physiological changes in infested crabs included significant differences (P = 0.001) in increments of wet body mass and a reduced growth rate over time compared with uninfested crabs. The specific oxygen consumption (M(O2)) in rested infested crabs significantly increased (31.29 +/- 5.8 micromol O2/kg/min) compared with the M(O2) in uninfested crabs (27.92 +/- 5.6 micromol O2/kg/min; P = 0.009). The heart rate of infested rested P. warreni was significantly lower (40.77 +/- 13.79 beats/min; P < 0.02) than that in uninfested crabs (61.09 +/- 29.02 beats/min) but the heart rate of infested crabs increased significantly with body mass (r = 0.53, P = 0.02). These findings suggest an interrelationship among organic pollution, microbial gill infestations, and specific pathological and physiological responses in the crab host. The role of P. warreni and its microbial gill communities as bioindicators of pollution are discussed.

Animals↗

Drug-induced methemoglobinemia during thoracoscopic lung biopsy.

Acquired methemoglobinemia occurs rarely in clinical practice. We present a case of a 57-year-old man who developed severe drug-induced methemoglobinemia after exposure to benzocaine spray and lidocaine jelly during intubation for an elective thoracoscopic lung biopsy. Information regarding the classifications, pathophysiology, diagnosis, and treatment of this entity is reviewed.

Aerosols↗

Toxicity of cadmium and zinc to Diplostomum spathaceum (Trematoda: Diplostomidae) cercarial survival.

The toxicity of cadmium and zinc at concentrations ranging from 0.1 to 10000 microg/l was investigated with cercariae of Diplostomum spathaceum at three temperatures (12, 20, 25 degrees C) and three levels of water hardness (distilled water, soft water, hard water). Under most environmental conditions survival of cercariae was reduced by increasing metal concentration. Increasing water hardness and decreasing water temperature caused an increase in the survival of both control and metal exposed cercariae. However, with decreasing temperature increased survival of metal-exposed cercariae above the control occurred at a number of low metal concentrations. Differences in the relative toxicity of cadmium and zinc to cercariae was dependent on the environmental conditions of exposure. The two heavy metals demonstrated little toxicity to cercariae during the period of maximum cercarial infectivity (0-5 h). The mechanisms of metal toxicity and their effects on cercarial survival are discussed.

Animals↗

Mapping visual cortex in monkeys and humans using surface-based atlases.

We have used surface-based atlases of the cerebral cortex to analyze the functional organization of visual cortex in humans and macaque monkeys. The macaque atlas contains multiple partitioning schemes for visual cortex, including a probabilistic atlas of visual areas derived from a recent architectonic study, plus summary schemes that reflect a combination of physiological and anatomical evidence. The human atlas includes a probabilistic map of eight topographically organized visual areas recently mapped using functional MRI. To facilitate comparisons between species, we used surface-based warping to bring functional and geographic landmarks on the macaque map into register with corresponding landmarks on the human map. The results suggest that extrastriate visual cortex outside the known topographically organized areas is dramatically expanded in human compared to macaque cortex, particularly in the parietal lobe.

Animals↗

Toxicity of cadmium and zinc to miracidia of Schistosoma mansoni.

The specific objectives of this study were to elucidate metal toxicity to hatching, survival and avoidance behaviour of Schistosoma mansoni miracidia. The toxicity of cadmium, zinc, and cadmium/zinc mixtures at concentrations ranging from 10000 to 10 microg/l was investigated. Metal mixture toxicity investigation was undertaken with equal concentrations of the metals. The hatching of miracidia from eggs was inhibited by concentrations of 1000-10000 microg/l of single metals. Metal mixtures had no effect on egg hatching. Survival of miracidia was reduced by increasing metal concentration except at concentrations of 10 microg/l for single metal toxicity where survival was increased above the control. Miracidia demonstrated a rapid avoidance behaviour when briefly exposed to heavy metals. The mechanisms of metal toxicity to miracidia are briefly discussed.

Animals↗

Toxicity of cadmium and zinc to encystment and in vitro excystment of Parorchis acanthus (Digenea: Philophthalmidae).

The toxicity of cadmium, zinc and cadmium/zinc mixtures at concentrations ranging from 1000 to 50000 microg/l were investigated against cercariae and metacercariae of Parorchis acanthus obtained from the dog whelk Nucella lapillus. Cercarial encystment at concentrations of 25000 microg/l or higher was significantly impaired by all test metals; however, at lower concentrations only zinc demonstrated toxicity. Mixtures of cadmium and zinc had a synergistic effect compared with single metal toxicity but only at 50000 microg/l. Excystment in vitro was only significantly affected by cercariae exposed to cadmium/zinc mixtures whilst encysting. Twenty-four h exposures of fully formed cysts had no effect on excystment in vitro. Effects on in vitro excystment rates over a 2 h period demonstrated widespread effects for cercariae-exposed P. acanthus. No effects were evident on excystment rates of cyst-exposed parasites.

Animals↗

Ammonia-induced cellular and immunological changes in juvenile Cyprinus carpio infected with the blood fluke Sanguinicola inermis.

Immunological and structural changes in the thymus and pronephros of Cyprinus carpio infected with the blood fluke, Sanguinicola inermis for 30 days, and exposed to 0.5 mg NH4+/1 for 48 and 168 h were investigated. Ultrastructural observations revealed cell disruption and highly vacuolated cytoplasm in the thymus. Of the cells that remained intact there was a significant increase in thrombocytes after 48 h exposure to the pollutant. In addition, there was a decrease in lymphocytes following exposure to ammonia at both time-periods studied. In contrast the pronephros of fish exposed to the pollutant underwent relatively mild changes in cellular architecture although ammonia and time of exposure had significant effects on the proportions of several leucocyte types. A significant decrease in neutrophils, thrombocytes and lymphocytes occurred in fish exposed to the pollutant for 168 h. Pronephric lymphocyte stimulation (cpm) by Con A and PWM increased in vitro, whereas the stimulation index was reduced in infected fish exposed to ammonia. Changes in the immune organs of S. inermis-infected carp treated with pollutant were both organ- and time-specific. The possible reasons for this are discussed and significance in relationship to parasitization assessed.

Ammonia↗

The potential use of the South African river crab, Potamonautes warreni, as a bioindicator species for heavy metal contamination.

In 1995, preliminary water and sediment analyses of the river bed and burrow sediments from 9 locations along the Mooi River, NW Province, South Africa had shown cadmium concentrations up to 0.009 mg l-1 +/- 0.003 and up to 0.33 and 0.89 weight % with scanning electron microscopy (SEM) and x-ray microanalysis. Samples of the adult river crab (Potamonautes warreni) were collected from the Mooi River at Noordbrug (26 degrees 40'S/27 degrees 05'E), 1 km north of Potchefstroom Town, and exposed to 0.2 or 2.0 mg Cd2+ l-1 in situ to determine tolerance, uptake and bioaccumulation of cadmium. Using flame atomic absorption spectroscopy (FAAS) the gills, haemolymph and digestive gland of naturally exposed P. warreni showed wet mass values of 0.74 +/- 0.27 microgram Cd2+ g-1, 0.007 +/- 0.007 microgram ml-1 and 0.12 +/- 0.09 microgram g-1 respectively. The tolerance of crabs to aqueous Cd reached its limit (ET50 = 42 hours) at 2.0 mg l-1 aqueous Cd exposure. At an exposure to 0.2 mg Cd2+ l-1 for 21 days, the greatest Cd (n = 11; 9.99 +/- 5.09 micrograms g-1 wet mass) and Cu concentrations (n = 11; 17.90 +/- 4.66 micrograms g-1 wet mass) were associated with the gills, and to a lesser extent the digestive gland (n = 11; 0.38 +/- 0.20 microgram g-1 wet mass), whereas concentrations of Zn were variable in both organs. In the haemolymph Cd levels were relatively small (n = 11; 0.012-0.006 microgram ml-1) with exposure and time and Cu, Zn concentrations varied. Changes in the uptake of Cd in P. warreni indicated that transport, storage and possibly regulatory mechanisms are likely to operate in adult crabs. The potential of P. warreni as a bioindicator species of pollution is also discussed.

Animals↗

Solid phase synthesis of 4-hydroxycinnamic acid and its derivatives for potential use in combinatorial chemistry: a novel route for the synthesis of 4-hydroxycinnamoyl coenzyme A and NMDA receptor antagonists.

Synthesis of 4-hydroxycinnamic acid 6 and its N-hydroxysuccinimide ester 8 has been carried out in high yield on solid support. Further development allowed the synthesis of 4-hydroxycinnamoyl CoA 1 in excellent overall yield. The utility of solid phase as a method for the synthesis of 4-hydroxycinnamic acid derivatives was demonstrated by the synthesis of a number of compounds including the NMDA receptor antagonists, N-(phenylalkyl)cinnamides 9 and 10.

Acyl Coenzyme A↗

Fecundity and egg output by Toxocara canis in the red fox, Vulpes vulpes.

The role of the red fox Vulpes vulpes in the dissemination of eggs of Toxocara canis into the environment is considered with reference to female worm fecundity and egg output in the faeces of infected foxes collected from four localities in southern England. A significant positive correlation was found between female worm size and the number of eggs in the uterus but there was no significant relationship between T. canis worm numbers and egg output in fox faeces. Reliable estimates of worm burdens in foxes could not, therefore, be determined from faecal egg counts alone. The highest mean egg output of 2145.0 epg recorded from adult foxes indicated that fox cubs are not necessarily the main sources of environmental contamination with T. canis eggs. Saturated magnesium sulphate was found to be a more effective flotation solution than zinc sulphate and sodium chloride for recovering eggs from fox faecal samples.

Animals↗

Monospecific helminth and arthropod infections in an urban population of brown rats from Doha, Qatar.

Parasitic infections were studied for the first time in an urban population of brown rats (Rattus norvegicus) from Doha. Only one species of helminth was found, the cestode Hymenolepis diminuta, and one ectoparasite, the flea Xenopsylla astia, from a sample size of 136 rats (52 males and 84 females). The prevalence of H. diminuta was 17.6%, increasing with host age but not in relation to host sex nor season of capture. Host age was a key factor in influencing abundance of infection, although there was a significant three-way interaction with season and host sex arising through heavy infections in juvenile male rats in the summer. The prevalence of X. astia was 45.6%, although both prevalence and abundance of infestations were season and host age dependent. In the winter prevalence and abundance were similar in both host age and sex groups, but in the summer both parameters of infestation were markedly higher among juveniles compared with adults. We found evidence for some association between these two species: H. diminuta was more prevalent among rats with fleas than among those without, although this association was season-, and independently sex- and age-dependent. There were no quantitative interactions and reasons for this are discussed in relation to the foraging and breeding behaviour of the brown rat in Qatar.

Animals↗

Corticocortical connections of visual, sensorimotor, and multimodal processing areas in the parietal lobe of the macaque monkey.

We studied the corticocortical connections of architectonically defined areas of parietal and temporoparietal cortex, with emphasis on areas in the intraparietal sulcus (IPS) that are implicated in visual and somatosensory integration. Retrograde tracers were injected into selected areas of the IPS, superior temporal sulcus, and parietal lobule. The distribution of labeled cells was charted in relation to architectonically defined borders throughout the hemisphere and displayed on computer-generated three-dimensional reconstructions and on cortical flat maps. Injections centered in the ventral intraparietal area (VIP) revealed a complex pattern of inputs from numerous visual, somatosensory, motor, and polysensory areas, and from presumed vestibular- and auditory-related areas. Sensorimotor projections were predominantly from the upper body representations of at least six somatotopically organized areas. In contrast, injections centered in the neighboring ventral lateral intraparietal area (LIPv) revealed inputs mainly from extrastriate visual areas, consistent with previous studies. The pattern of inputs to LIPv largely overlapped those to zone MSTdp, a newly described subdivision of the medial superior temporal area. These results, in conjunction with those from injections into other parietal areas (7a, 7b, and anterior intraparietal area), support the fine-grained architectonic partitioning of cortical areas described in the preceding study. They also support and extend previous evidence for multiple distributed networks that are implicated in multimodal integration, especially with regard to area VIP.

Animals↗

Mapping of architectonic subdivisions in the macaque monkey, with emphasis on parieto-occipital cortex.

The intraparietal sulcus (IPS) of the macaque monkey contains numerous areas associated with different aspects of cortical function, including motor control as well as visual, somatosensory, vestibular, and possibly auditory processing. This study focuses largely on the architectonic organization of areas within and near the IPS, but also examines remaining portions of the hemisphere with which the IPS is interconnected. We charted the location of up to 72 architectonically distinct areas plus numerous architectonic zones in individuals over a region covering most of the cortical hemisphere. Identified cortical subdivisions (areas plus zones) were represented on computationally generated flat maps in relation to gyral and sulcal geography, thereby facilitating the analysis of consistent as well as variable aspects of the sizes and relative positions of subdivisions across animals. Using myelin and Nissl stains, plus immunohistochemical staining with the SMI-32 antibody, 17 architectonic subdivisions were identified that are largely or entirely contained in the intraparietal and parieto-occipital sulci. This includes four newly identified zones: a heavily myelinated lateral occipitoparietal zone, termed LOP; a strongly SMI-32 immunoreactive zone termed 7t (near the tip of the IPS); plus medial and lateral subdivisions (VIPm and VIPl) of ventral intraparietal area (VIP), which was previously regarded as an anatomically homogeneous area. Within the superior temporal sulcus, we identified a densely myelinated zone termed the dorso-posterior subdivision of the medial superior temporal area (MSTdp) that bordered middle temporal area (MT). We charted the extent of numerous other architectonically defined subdivisions throughout the cortical hemisphere by using criteria largely based on previous studies, but in some instances involving revised or expanded identification criteria.

Animals↗

Selective kappa-opioid antagonists related to naltrindole. Effect of side-chain spacer in the 5'-amidinoalkyl series.

The study of kappa-opioid receptor function in vivo has been hampered by the limited choice of selective kappa-antagonists. Recently discovered kappa-antagonists have not yet been utilised in vivo. We here report the synthesis and in vitro evaluation of a new amidine derivative of naltrindole. It showed substantially greater kappa-selectivity in binding assays than known analogues with shorter spacer in the amidine side chain. This indicates that in nor-BNI and related selective kappa-antagonists, the second basic centre may not be ideally located.

Amidines↗

3-Deoxyclocinnamox: the first high-affinity, nonpeptide mu-opioid antagonist lacking a phenolic hydroxyl group.

The C(3)-substituent in morphinan opioids is of critical importance; the 3-OH group is usually associated with very much higher affinity for mu-receptors than H or -OMe. However in this series of 14beta-cinnamoylamino derivatives the codeinones (e.g. methoclocinnamox, MC-CAM) had unexpectedly high mu-opioid receptor affinity, similar to that of the morphinone (clocinnamox, C-CAM). The current report relates to the synthesis and in vitro evaluation of deoxyclocinnamox (DOC-CAM) which acted as a high-affinity opioid antagonist similar to C-CAM but with greater mu selectivity. Thus it appears that the C(3)-substituent does not play a major role in the binding of the 14beta-cinnamoyl series and that the cinnamoyl group itself may in fact be the dominant binding feature.

Animals↗

Structural constraints imposed by a non-native disulfide cause reversible changes in rhodopsin photointermediate kinetics.

Suspensions of bovine rhodopsin in 2% lauryl maltoside detergent were treated with Cu(phen)(3)(2+) to form a disulfide bridge between cysteines 140 and 222 which occur naturally in the bovine rhodopsin sequence. Absorption difference spectra were collected after excitation with a pulse of 477 nm light on the time scale from 1 micros to 690 ms, and the results were analyzed using global exponential fitting. Only two exponentials could be fit to data from the Cu(phen)(3)(2+)-treated rhodopsin, while three exponentials were needed to fit data either from untreated rhodopsin or from Cu(phen)(3)(2+)-oxidized rhodopsin after further dithiothreitol reduction. Dithiothreitol treatment of rhodopsin which had not been previously oxidized with Cu(phen)(3)(2+) had no effect on the observed kinetics. Since the 140-222 disulfide has previously been shown to block transducin activation, its effects on rhodopsin activation are of considerable interest. Cu(phen)(3)(2+) treatment favors formation of the meta I(380) intermediate relative to meta I(480) and slows formation of meta II from meta I(380). This suggests that the protein change involved in meta I(380) formation is similar to the structural constraint introduced by the 140-222 disulfide. These results show that formation of disulfides in rhodopsin has potential as a tool for discriminating between the three isochromic, 380 nm absorbing intermediates involved in rhodopsin activation and for gaining insight into how their structures differ.

Animals↗

Structural determinants of opioid activity in the orvinols and related structures: ethers of orvinol and isoorvinol.

A series of ethers of orvinol and isoorvinol has been prepared and evaluated in opioid receptor binding and in vitro functional assays. The most striking finding was the very large difference in kappa-opioid receptor activity between the diastereomeric ethyl ethers: 46-fold in binding, 150-fold in GPI, and 900-fold in the [(35)S]GTPgammaS assay in favor of the (R)-diastereomer. Additionally in the (R)-series there was a 700-fold increase in kappa-agonist potency in the [(35)S]GTPgammaS assay when OEt was replaced by OBn. The data can be explained in a triple binding site model: an H-bonding site, a lipophilic site, and an inhibitory site with which the 20-Me group in the (S)-ethers may interact. It appears that kappa-agonist binding of the orvinols avoids the inhibitory site in the intramolecular H-bonded conformation.

Analgesics, Opioid↗

Effect of salinity on hatching, survival and infectivity of Anguillicola crassus (Nematoda: Dracunculoidea) larvae.

The effect of salinity on hatching, larval survival and infectivity of Anguillicola crassus was studied under experimental conditions using eggs obtained from naturally infected eels. Egg hatching rate, second-stage larval survival and larval infectivity were maximal in fresh water and declined with increase in salinity. Larvae survived up to 100 d in fresh water, 70 d in 50 % sea water and 40 d in 100% sea water. Infectivity experiments demonstrated that salinity influenced transmission success throughout the life cycle by decreasing total infectivity of the larval population in utero within female A. crassus and when larvae were free-living in the aquatic environment. Infectivity was age-dependent in relation to salinity. Larvae were infective to intermediate and paratenic hosts for up to 80 d in fresh water, 21 d in 50% sea water and up to 8 d in 100% sea water. The data confirm field observations that infection levels decrease with an increase in salinity. The study contributes to experimental verification of the colonization abilities of A. crassus and supports the hypothesis that A. crassus can be disseminated and transmitted in brackish water. The importance of regular monitoring and stringent hygiene practices in the transportation of eels is emphasized.

Air Sacs↗