PubMed Health⌕ Search

Biomedical subjects

J L Bennett

Publications and source records attributed to J L Bennett.

At least 55 records · Page 3Linked to original sources
PubMed1994

Predictors of upper gastrointestinal bleeding in patients with schistosomal periportal fibrosis.

A case-control study was conducted between 1985 and 1987 in the Gezira-Managil area of central Sudan to assess the major predictors of haematemesis. Eighty-four patients who had suffered at least one attack of oesophageal bleeding and had schistosomal periportal fibrosis demonstrated by ultrasonography were compared with 173 subjects without bleeding but with ultrasonographic evidence of periportal fibrosis. A splenic longitudinal dimension of more than 11 cm, periportal fibrosis worse than grade I and varices more than grade I were independently associated with a significant risk of variceal bleeding. Age, sex, presence of a palpable liver and portal vein diameter were not associated with a significant risk of bleeding after adjustment for potential confounding variables. Factors identified in this study could be helpful in the prophylactic management of patients with complicated schistosomiasis.

Adult↗
PubMed1994

Schistosoma mansoni: myogenic characteristics of phorbol ester-induced muscle contraction.

The myogenic nature of phorbol ester-induced muscle contractures of Schistosoma mansoni was investigated using muscle physiology and electrophysiological techniques. The contracture is dependent of extracellular Ca2+, is blocked by Ca2+ channel blockers, and appears to be associated with an increase in the permeability of the muscle to Ca2+ but not to Na+ or H+. The musculature is not depolarized during phorbol ester-induced contracture, but surface electrical activity decreases. Threshold treatments of phorbol ester and depolarization or praziquantel produce synergistic contractures of the parasite. The contracture could not be explained by altered release of or sensitivity to putative neurotransmitters, decreased Ca2+ efflux, or an increase in the sensitivity of the contractile system to Ca2+. These results support the hypothesis that activation of protein kinase-C in the schistosome with phorbol esters leads to muscle contracture by enhancing sarcolemmal Ca2+ channel activity.

Acetylcholine↗
PubMed1994

Serotonin and its requirement for maintenance of contractility in muscle fibres isolated from Schistosoma mansoni.

Muscle fibres isolated from adult Schistosoma mansoni contracted in a dose-dependent manner when exposed to elevated K+ with a maximum response obtained with 25 mM K+. These contractions were dependent on extracellular Ca2+ since Co2+ (5 mM) or nicardipine (1 microM) blocked the high K+ contractions. Serotonin (300 nM or higher) was required for maintenance of high K+ contractions. With concentrations of serotonin less than 300 nM the response was dose dependent. 5-Methoxytryptamine or alpha-methylserotonin at 1 microM as well as 10 microM tryptamine were able to substitute for serotonin, but 1 microM 5-carboxyamidotryptamine was ineffective. The order of potency for antagonists (10 microM) was: methiothepin > metergoline > Ly-278,584 = ketanserin. This pattern of responsiveness does not fit well with any known mammalian serotonin receptor subtype. Since forskolin, an adenylate cyclase activator, is able to mimic the action of serotonin and H89, a protein kinase inhibitor, is able to block the effect of serotonin, the effect of serotonin on contractility of the muscle may be via a cAMP-dependent pathway.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Platyhelminth FMRFamide-related peptides (FaRPs) contract Schistosoma mansoni (Trematoda: Digenea) muscle fibres in vitro.

Molluscan FMRFamide and two recently discovered platyhelminth FMRFamide-related peptides (FaRPs), GNFFRFamide from the cestode Moniezia expansa and RYIRFamide from the terrestrial turbellarian Artioposthia triangulata, cause dose-dependent contractions of individual muscle fibres from Schistosoma mansoni in vitro. The most potent FaRP tested was the turbellarian peptide RYIRFamide, which produced a concentration-dependent effect between 10(-9) and 10(-7) M. FMRFamide and GNFFRFamide were less potent, inducing contractions between 10(-8)-10(-6) M and 10(-7)-10(-5) M respectively. The contractile effect of each of these peptides was blocked by the presence of 1 microM FMR-D-Famide. FMRF free acid did not elicit contraction of the muscle fibres. The FaRP-induced contractions did not occur if the Ca2+ was omitted and 0.5 microM EGTA was added to the extracellular medium. The FaRP-induced contractions were not blocked by the Ca2+ channel blockers nicardipine, verapamil or diltiazem, although high K+-induced contractions of these fibres were blocked by nicardipine. These data indicate the presence of FaRP receptors on schistosome muscle fibres and demonstrate their ability to mediate muscle contraction. The action of these endogenous flatworm peptides on schistosome muscle is the first demonstration of a direct excitatory effect of any putative neurotransmitter on the muscle of a flatworm, and establishes a role for FaRPs in neuromuscular transmission in trematodes. In addition, it provides the first evidence that the peptidergic nervous system is a rational target for chemotherapeutic attack in parasitic platyhelmiths.

Amino Acid Sequence↗
PubMed1994

Significant reduction in chloroquine bioavailability following coadministration with the Sudanese beverages Aradaib, Karkadi and Lemon.

Chloroquine bioavailability in healthy males was examined following oral coadministration of 600 mg with three common Sudanese beverages, Aradaib (Tamarindus indica), Karkadi (Hibiscus sabdarifa) and Lemon (Citrus limetta) and drinking water. The tablets and beverages were taken on an empty stomach after an overnight fast. The plasma chloroquine concentrations were measured by HPLC. The extent and rate of chloroquine bioavailability were described by the area under the plasma concentrations versus time curve (AUC), the peak plasma concentration (Cmax) and with the time to reach Cmax (Tmax), respectively. The mean (+/- S.E.) AUC values after administration with water (control) and Aradaib, Karkadi and Lemon, respectively, were 7.52 +/- 0.87, 2.60 +/- 0.24, 2.16 +/- 0.30 and 2.41 +/- 0.29 mg.h/L. The corresponding mean Cmax values were 553 +/- 17.8, 184 +/- 21.3, 148 +/- 14.1 and 210 +/- 17.4 mg/L and the corresponding Tmax values were 3.0 +/- 1.0, 3.2 +/- 1.2, 2.6 +/- 0.8 and 2.5 +/- 1.0 h. The results indicate a statistically significant reduction in the AUC and Cmax of chloroquine as a result of a coadministration with each of the three beverages. A parallel reduction in the drugs antimalarial efficacy might be expected.

Adult↗
PubMed1993

Characterization of mevalonate-labeled lipids isolated from parasite proteins in Schistosoma mansoni.

Adult paired schistosomes incubated for 3 days in radiolabeled mevalonate can effectively label at least 2 major proteins with apparent sizes of 25 and 43 kDa. The 25-kDa mevalonate-labeled proteins comigrated with proteins that could be labeled with GTP. The lipids attached to these proteins were removed and resolved by HPLC and found to comigrate with known samples of farnesol and geranylgeraniol. Homogenates of the schistosome when incubated with labeled farnesol pyrophosphate effectively labeled a protein(s) with an apparent molecular weight of 43 kDa while homogenates incubated in the presence of labeled geranylgeranyl pyrophosphate-labeled schistosome proteins with an apparent molecular weight of 25 kDa. Our results demonstrate that Schistosoma mansoni has the ability to covalently attach farnesol and geranylgeranyl to low-molecular weight proteins.

Animals↗
PubMed1993

Serotonin and acetylcholine: further analysis of praziquantel-induced contraction of magnesium-paralysed Schistosoma mansoni.

The nature of stimulus-induced flaccid paralysis produced in Mg(2+)-paralysed Schistosoma mansoni was investigated. Serotonin induced a dose-dependent, heterologous flaccid paralysis with an IC50 of 600 nM. This flaccid paralysis was a function of the extracellular Mg2+:Ca2+ ratio and was reversible. Tonic contractions produced by phorbol-12,13-dibutyrate or 60 mM K+ were reversed by the application of serotonin and flaccid paralysis was induced. These actions of serotonin were mimicked by forskolin and synergized by IBMX but the potassium channel blocker, 3,4-DAP, did not produce flaccid paralysis. When Mg(2+)-paralysed parasites were stimulated with 3,4-DAP, IBMX produced a dose-dependent flaccid paralysis with an IC50 of 11 microM. Membrane permeable analogues of cAMP and cGMP did not synergize with IBMX. Cholinergic agonists, but not other inhibitory substances, prevented the serotonin- and forskolin-induced and the IBMX-synergized flaccid paralysis but not that produced by praziquantel. The possible interactions of these agents with the muscle are discussed.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Voltage-gated currents in muscle cells of Schistosoma mansoni.

Three morphologically distinct types of muscle fibres isolated from the platyhelminth Schistosoma mansoni have been studied with whole cell current- and voltage-clamp techniques. Fibres showed a marked time-dependent decrease in membrane resistance in response to depolarizing current injections. Voltage-clamp experiments revealed the presence of two distinct voltage-gated outward currents. The most prominent current is a slowly activating, slowly and incompletely inactivating potassium current similar to delayed rectifier currents which have been described in a variety of cell types from a variety of organisms. Also present is a faster activating, quickly and completely inactivating potassium current that shares functional characteristics with 'A'-currents. All three of the cell types studied possess a delayed rectifier current, but only two of the three types have 'A'-currents. Though depolarization with high K+ leads to contraction of the dispersed fibres, no voltage-gated inward currents could be detected by whole cell voltage-clamp under any of our conditions.

Animals↗
PubMed1993

Secondary structure of RNase MRP RNA as predicted by phylogenetic comparison.

RNase MRP is a ribonucleoprotein endoribonuclease that has been shown to cleave mitochondrial primer RNA sequences from a variety of sources. The bulk of RNase MRP activity is found in the nucleus where its function remains unknown. Two different approaches have resulted in predictions of distinct secondary structures for RNase MRP RNA. In order to analyze more definitively the higher-order structure of RNase MRP RNA, we have conducted a phylogenetic comparison of the available RNase MRP RNA sequences from human, mouse, rat, cow, toad, and yeast. The resulting secondary structure shares features in common with previously described structures for prokaryotic and eukaryotic RNase P RNAs (1) and RNase MRP RNAs (2, 3). In addition, the phylogenetic structure is consistent with available chemical modification data on RNase MRP RNA and with the detailed analysis of the To antigen binding domain located near the 5' end of the RNase MRP RNA. The structure is not limited to RNase MRP RNAs, but can be expanded to cover both eukaryotic RNase P RNAs and RNase P/MRP RNAs from plants.

Animals↗
PubMed1993

Expression of a retroposon-like sequence upstream of the putative Trypanosoma brucei variant surface glycoprotein gene expression site promoter.

We have cloned the region spanning the putative promoter from two variant surface glycoprotein gene expression sites that are at each end of chromosome M4 of Trypanosoma brucei IsTat 7. Both expression sites contain a retroposon-like sequence (ESR) pseudogene whose 3' end is approximately 30 bp upstream of the putative expression site promoter. The ESRs from both expression sites share considerable sequence homology and are related to LINE-like elements, especially the T. brucei ingi retroposon. Other ESRs are located on large, but not intermediate or mini-, chromosomes in the IsTaR 1 serodeme, and the total copy number is 10 to 20, similar to that estimated for variant surface glycoprotein expression sites. No DNA rearrangements in the vicinity of the ESR and putative expression site promoter were detected following antigenic switches in the IsTaR 1 serodeme. ESR transcripts are present in bloodstream, but not procyclic, forms. Variation in transcript size and sequence between bloodstream variant antigenic types implies that only the ESR from the active expression site is transcribed. This pattern of expression reflects that of sequences downstream of the putative expression site promoter, suggesting that the region of coordinately controlled expression extends upstream of this promoter.

Amino Acid Sequence↗
PubMed1993

Liver sonography in an area endemic for schistosomiasis haematobium.

Through the use of portable ultrasonography, eight cases (2%) of periportal fibrosis were identified in a random sample of 400 subjects selected from a village with a high prevalence and morbidity due to schistosomiasis haematobium in the White Nile Province of Sudan. In contrast, 36 cases (15%) of fibrosis were seen in an area with a similar prevalence and morbidity due to schistosomiasis mansoni in the Gezira Managil region of Sudan. Although there was only one case of Schistosoma mansoni as determined by repeated stool examination of the entire sample population in the first village, the majority of those with fibrosis and age-matched controls showed serologic evidence of active S. mansoni infection. This led to the conclusion that the cases of periportal fibrosis seen in the White Nile Province are most probably due to S. mansoni rather than to S. haematobium.

Adolescent↗
PubMed1992

Characterization of a Xenopus laevis ribonucleoprotein endoribonuclease. Isolation of the RNA component and its expression during development.

In order to facilitate studies of the assembly and transport of the site-specific RNase mitochondrial RNA processing (MRP) ribonucleoprotein, we have characterized it from Xenopus laevis cells. X. laevis RNase MRP displayed a similar spectrum of cleavage activity to that produced by previously isolated mammalian nuclear enzymes. A 277-nucleotide RNA component of the ribonucleoprotein was identified; the gene for the RNA was isolated, sequenced, and found to be 66 and 63% similar to mouse and human RNase MRP RNAs, respectively. Despite the evolutionary distance from its mammalian counterparts, X. laevis RNase MRP RNA contains five regions of homology to the mammalian RNase MRP RNA. Four of these regions correspond to those previously identified as conserved between RNase MRP and RNase P RNAs; the fifth encompasses nucleotides recently discovered to be sufficient for autoantigen binding. The expression and assembly of Xenopus RNase MRP RNA were examined in frog oocytes and developing embryos. RNase MRP RNA was expressed throughout oogenesis; it started to accumulate at stage I and reached a maximum in stage IV. During embryogenesis RNase MRP RNA expression began to elevate at approximately stage 22 and continued to rise through the swimming tadpole stage. When injected into the nucleus of mature oocytes, the X. laevis RNase MRP RNA gene was expressed accurately, and transcripts were packaged into immunoprecipitable particles.

Animals↗
PubMed1992

High-performance liquid chromatographic method for the analysis of Oltipraz in human serum and urine.

A rapid, sensitive procedure for the analysis of Oltipraz in serum and urine using high-performance liquid chromatography was developed. The proposed method illustrates recovery of Oltipraz from biological fluids was greater than 80%. Detection and separation of Oltipraz required as little as 1 ml of serum or urine. Oltipraz was detectable when 2 ng or more of drug was present in 1 ml of serum or urine; the method is highly reproducible when 5 ng/ml or more Oltipraz is present in the biological fluid.

Chromatography, High Pressure Liquid↗
PubMed1992

Clinical pharmacology studies of oltipraz--a potential chemopreventive agent.

Pharmacological studies on Oltipraz [4-methyl-5(pyrazinyl-2)-1-2-dithiole-3-thione)] were conducted with normal healthy subjects using various doses and schedules. Administration of single doses (1, 2 and 3 mg/kg) resulted in detectable drug levels in the serum (mean peak serum concentrations 16, 61 and 205 ng, respectively) and urine. The t1/2 was short (4.4, 4.1 and 5.3 hours respectively) and no steady state was achieved after multiple daily doses for 12 days. Introduction of a loading dose during the first day produced a steady state when 1.5 and 2.0 mg/kg/day were used. Daily administration of Oltipraz sustained the steady state with insignificant variations. Consumption of a high fat diet increased the serum and urine concentrations of Oltipraz (30-60%) compared to the low fat diet. Two subjects experienced flatulence during the administration of the drug. One subject developed numbness and pain in the thumbs with occurrence of small purplish-black spots resembling those observed in subacute endocarditis. These changes disappeared 10 days after discontinuation of the drug. No changes in peripheral blood counts, biochemical profile or thyroid function tests were observed after four weeks of Oltipraz. Further studies with a larger number of healthy subjects are needed for clarification of the safety and biological efficacy of small doses of Oltipraz during chronic administration.

Adult↗
PubMed1992

Schistosoma mansoni: patch-clamp study of a nonselective cation channel in the outer tegumental membrane of females.

An apparent ion channel with a conductance of 295 pS is present in isolated inside-out patches of outer tegumental membrane taken from female Schistosoma mansoni. With positive voltages applied to the intracellular face of the patch, percentage open time for the channel was 0 to 50; with negative voltages applied, percentage open time was greater than 99. Step changes in applied voltage characteristically induced opening-closing activity. However, there was no maintained applied voltage at which there was a high level of sustained opening-closing activity. The 295 pS conductance was by far the most commonly occurring conductance but it appears to result from cooperativity among several channels, the unitary conductance for the channel averaging 95 pS. Alterations in the Na+ or K+ concentration ratios changed the reversal potential for this conductance but alterations in the Cl- concentration did not. From this it is concluded that this channel is selective for Na+ or K+ over Cl- and it appears to be a nonselective cation channel.

Animals↗
PubMed1992

Praziquantel: The enigmatic antiparasitic.

Praziquantel (PZQ), a pyrazinoisoquinoline, was introduced as a novel anthelmintic in 1975. PZQ is currently the drug of choice for the treatment of a wide range of both veterinary and human trematode and cestode infections, including human schistosomiasis. Current estimates suggest that 150 million humans are infected with schistosomes, and it is expected that PZQ will play the lead role in chemotherapeutic control of those infections. Despite the time that has passed since its introduction and its obvious importance in global health care, it is not yet understood why PZQ is so selective and effective. The target molecules for PZQ have not been defined, nor are the sites of its effects within the parasites known. Here, Tim Day, James Bennett and Ralph Pax summarize some of the progress that has been made toward reaching these objectives in recent years.

Journal Article↗
PubMed1992

Praziquantel: physiological evidence for its site(s) of action in magnesium-paralysed Schistosoma mansoni.

The mechanism whereby praziquantel produces a contraction and subsequent flaccid paralysis (a loss of sensitivity to subsequent stimuli) of Schistosoma mansoni in a medium containing an elevated Mg2+:Ca2+ ratio was investigated. In RPMI, praziquantel produced a concentration-dependent tonic contraction of the parasite with an EC50 of 200 nM. Magnesium inhibited the contraction in such a manner as to convert the tonic contraction to a phasic one without altering the peak force generated. The Mg(2+)-dependent block was non-competitive with praziquantel but was competitive with extracellular Ca2+, ratios of 7.5:1;Mg2+:Ca2+ being needed to inhibit the tonic contraction and to induce flaccid paralysis. Flaccid paralysis was associated with a reduced ability of the parasite to take up 45Ca2+ from the bath compared to parasites that had not entered into flaccid paralysis and flaccid paralysis was reversible. Recovery from flaccid paralysis was accelerated by treatments that are expected to increase Ca2+ uptake by the parasite. At a concentration of 500 nM, praziquantel produced 2 distinct phasic contractions in intact parasites incubated in an elevated [Mg2+] medium but only 1 phasic contraction in parasites lacking their surface tegumental membranes. In zero Ca2+ I-RPMI, 10 microM praziquantel produced a phasic contraction of intact parasites but did not stimulate contraction of detegumented parasites until Ca2+ was reintroduced into the bath. These results indicate that praziquantel interacts with specific Ca(2+)-permeable sites in the tegumental and sarcoplasmic membranes of the parasite and that under these conditions of elevated Mg2+:Ca2+ ratios, these sites become blocked by Mg2+, leading to flaccid paralysis of the parasite.

Animals↗