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Biomedical subjects

J L Bennett

Publications and source records attributed to J L Bennett.

At least 37 records · Page 2Linked to original sources
PubMed1997

Digital video image capture in establishing positive identification.

Positive identification of skeletonized, decomposed, or disfigured victims lacking clinical records is a difficult endeavor. However, videotapes of family and social activities can be analyzed using the frame isolating technique of video image capture by inexpensive means. A rare skeletal Class III malocclusion and dental peculiarities in a decomposing 3-year old lacking a clinical history were compared to videotapes taken of a suspected victim shortly prior to her disappearance. Overlaying transparent dental tracings from digitized skeletal remains onto selected frames of the videotape (and reversing this process) produced the identification and hastened the entire investigation.

Child, Preschool↗
PubMed1996

Epstein-Barr virus--associated acute autonomic neuropathy.

A 44-year-old man developed blurry vision, photosensitivity, orthostasis, constipation, and acrodysesthesias after a febrile illness. The neurologic examination and ancillary studies were consistent with a dysautonomic small fiber neuropathy. The cerebrospinal fluid (CSF) contained both Epstein-Barr virus (EBV) DNA and antibody to EBV. This is the first report of an acute autonomic neuropathy with documented EBV infection in CSF.

Adult↗
PubMed1996

Schistosoma mansoni: L-glutamate-induced contractions in isolated muscle fibers; evidence for a glutamate transporter.

Schistosoma mansoni muscle fibers contract in response to L-glutamate in a dose-dependent manner (10(-6)-10(-3) M). L-aspartate and D-aspartate are likewise effective in eliciting contraction of the fibers. Mammalian glutamate receptor agonists produce little or no contraction at concentrations as high as 1 mM. In addition, common glutamate receptor antagonists do not inhibit the contraction induced by L-glutamate. However, amino acids known to be substrates for the high-affinity glutamate transporter elicit contraction of the muscle fibers. These results suggests that there is a high-affinity glutamate transporter on the muscle fibers which, because of its electrogenic nature, is causing depolarization and contraction. This is supported by the evidence that contraction induced by L-glutamate is dependent on extracellular Ca2+ and is blocked by nicardipine (10 microM). [3H]L-glutamate is taken up in a dose-dependent manner by the muscle fiber preparation. This uptake is also time- and temperature-dependent. Both the L-glutamate-induced contractile response and [3H]L-glutamate uptake are Na(+)-dependent and can be blocked by specific inhibitors of the high-affinity transporter. This experimental evidence supports the hypothesis that there is a Na(+)-dependent high-affinity glutamate transporter on the schistosome muscle membrane.

ATP-Binding Cassette Transporters↗
PubMed1996

A rab-related GTP-binding protein in Schistosoma mansoni.

Schistosomiasis is a parasitic disease initiated by the deposition of eggs in host tissues by the blood fluke Schistosoma. A gene encoding a low-molecular weight GTP-binding protein (LMWGP) was cloned from Schistosoma mansoni using a polymerase chain reaction (PCR)-based strategy. The gene was termed smrab (Schistosoma mansoni rab-related protein). Northern blot analysis hybridizes smrab cDNA with a 1.5-kb band of mRNA; this mRNA is abundantly expressed in male schistosomes, while only slightly in females. The deduced amino acid sequence of smrab shares ca. 70% homology with that of several rab-related LMWGPs. Smrab terminates in a CCXXX motif, which is one of several signals for post-translational isoprenoid modification by geranylgeranyl protein transferase (GGPT) type II. A GGPT assay with in vitro translation product confirms that smrab is geranylgeranylated. Recombinant expression of smrab in the pET3a expression vector yields insoluble protein which migrates as a 23-kDa band on SDS-PAGE. N-terminal sequence information of the recombinant protein matches the predicted amino acid sequence of smrab. GTP-binding analysis indicates that the recombinant protein binds GTP. Therefore, smrab meets the criteria recently established for acceptance into the ras superfamily of GTP-binding proteins (Kahn, R.A., Der, C.J. and Bokoch, G.M. (1992) The ras superfamily of GTP-binding proteins: guidelines on nomenclature. FASEB J. 6, 2512-2513, Ref. [21]).

Alkyl and Aryl Transferases↗
PubMed1996

Schistosome resistance to praziquantel: Fact or artifact?

Praziquantel is the current drug of choice for human schistosomiasis. Recent reports from laboratory and field studies concerning reduced praziquantel efficacy against Schistosoma mansoni have generated some controversy. The prevailing question is whether the emergence of strains of schistosome resistant to praziquantel is a fact, or an artifact resulting from erroneous field or laboratory experimentation. In this article, Padraic Fallon, Liang-feng Tao, Magdi Ismail and James Bennett examine the available evidence for schistosome resistance to praziquantel. Contributory factors to the schistosomicidal activity of praziquantel, which may interfere with evaluation of drug efficacy or resistance, are also considered.

Journal Article↗
PubMed1996

Cholinergic inhibition of muscle fibres isolated from Schistosoma mansoni (Trematoda:Digenea).

Cholinergic compounds inhibit FMRFamide-induced contractions in dispersed muscle fibres isolated from adult Schistosoma mansoni. Acetylcholine (ACh) was the most effective cholinergic agonist tested with an EC50 < 100 nM. Less effective were propionylcholine and arecoline with EC50 < 1 microM and butyrylcholine and carbachol with EC50 < 10 microM. Choline, muscarine, pilocarpine, nicotine, DMPP (1,1-dimethylphenylpiperazine) and levamisole were all ineffective. Amongst tested antagonists, d-tubocurarine (100 microM), mecamylamine (1 mM), scopolamine (1 mM) and quinuclidinyl benzilate (10 microM) were all ineffective. Bicuculline, picrotoxin and strychnine were also ineffective. However alpha-bungarotoxin, at 100 nM, was able to block the inhibitory ACh effect. From these data it appears that the cholinergic receptor on the schistosome muscle fibres may be of the nicotinic type, but that its pharmacology is different from that of nicotinic receptors of vertebrates as well as of nematodes or a variety of other invertebrates.

Acetylcholine↗
PubMed1996

Neuromuscular physiology and pharmacology of parasitic flatworms.

The trematode and cestode flatworms include numerous parasitic forms of major medical and economic importance. A better knowledge of the neuromuscular physiology of these animals could lead to development of new control measures against these parasites. Since these animals are near the stem from which all other animals have evolved, better knowledge of these animals could also yield valuable information about the early evolution of nerve and muscle systems in the animal kingdom. This review focuses on what is known about the characteristics of the somatic muscle in these animals. The anatomy of the muscles is described along with a review of current information about their electrophysiology, including descriptions of the ion channels present. Also included is a summary of recently acquired data concerning the nature of serotonin, peptide, acetylcholine and glutamate receptors on the membranes of the muscles.

Animals↗
PubMed1996

Rheological and microvascular parameters in diabetic peripheral neuropathy.

1. In order to determine whether rheological changes occur in neuropathic diabetic patients in the absence of smoking, proteinuria, retinopathy or other factors thought to influence haemorheology, three groups of subjects were studied; 24 non-diabetic control subjects (C), 24 non-neuropathic (D) and 24 neuropathic (N) diabetic patients. The groups were matched for age, sex, type and duration of diabetes. No patient or control was a current smoker. No patient had clinically detectable retinopathy or microalbuminuria. Neuropathy was defined as a peroneal conduction velocity < 40 ms-1. All subjects were tested resting semi-recumbent after a light breakfast. 2. There were no significant differences in rheological or microvascular parameters between uncomplicated diabetic patients and non-diabetic control subjects, although peroneal nerve motor conduction velocity was significantly reduced in otherwise uncomplicated diabetic patients [C 51.7 +/- 6.0 ms-1 (mean +/- SD) versus D 45.1 +/- 5.2 ms-1 (P < 0.05 C versus D)]. 3. Transcutaneous oxygen and laser Doppler flux measured at 44 degrees C were higher in control subjects than in neuropathic diabetic patients [C 76 +/- 16 mmHg versus D 71 +/- 10 mmHg versus N 63 +/- 9 mmHg, and C 72 +/- 40 flow units versus D 64 +/- 41 flow units versus N 50 +/- 26 flow units respectively (both P not significant C versus D, P < 0.05 N versus C). 4. Erythrocyte aggregation, plasma viscosity and plasma fibrinogen were all significantly higher in the neuropathic diabetic patients compared with non-diabetic control subjects (all P < 0.05 N versus C). Erythrocyte filtration was not significantly different between groups but was lower in diabetic patients. Whole-blood viscosity (corrected to 45% haematocrit) was significantly higher at both high (100 s-1) and low (1 s-1) shear rates in neuropathic diabetic patients than in non-diabetic control subjects (both P not significant C versus D, P < 0.05 N versus C). There were no significant differences in whole-blood viscosity at a shear rate of 0.01 s-1. 5. In summary, there were no significant differences in rheological or microvascular parameters between matched groups of uncomplicated diabetic patients and control subjects, but erythrocyte aggregation, fibrinogen and plasma and corrected whole-blood viscosity were all significantly different in neuropathic diabetic patients compared with control subjects, as were assessments of microvascular flow. These results suggest that haemorheological changes are associated with disturbances of microvascular flow and diabetic peripheral neuropathy in the absence of other diabetic complications.

Adult↗
PubMed1996

The effectiveness of annual versus biennial mass chemotherapy in reducing morbidity due to schistosomiasis: a prospective study in Gezira-Managil, Sudan.

The most serious complication of schistosomiasis is periportal fibrosis, which affects a large number of subjects in endemic areas. Population-based chemotherapy remains the most effective way of controlling this disease. In an attempt to find the best way to deliver chemotherapy to the endemic population, we compared the impact of repeated annual versus biennial mass chemotherapy on morbidity due to schistosomiasis in two villages in Gezira, Sudan. One village was given five rounds of mass chemotherapy annually in the years 1990-1994 while the other village was given three rounds of mass chemotherapy biennially from 1988 to 1994. Before treatment, these villages had similar intensity of infection and prevalence. One round of either annual or biennial treatment reduced the intensity of infection, but not prevalence or morbidity. After two rounds of annual chemotherapy, infection rates, bloody diarrhea, and fibrosis in those 20 years of age and less were significantly reduced. Two rounds of biennial chemotherapy had a similar effect on rates and bloody diarrhea; however, fibrosis was reduced only after the third round of biennial chemotherapy. Prevalence of hepatosplenomegaly increased after both treatment regimens. Reinfection was most prominent in those 5-14 years of age. These findings support the general notion that repeated chemotherapy may be needed in areas of high transmission of schistosomiasis. We recommend two rounds of annual mass chemotherapy to significantly reduce infection and morbidity.

Adolescent↗
PubMed1996

Characterization of isolates of Schistosoma mansoni from Egyptian villagers that tolerate high doses of praziquantel.

To determine if resistance/tolerance to the antischistosomal drug praziquantel (PZQ) is appearing in Egyptian villages within the Nile delta region, where it has been used extensively, we treated 1,607 infected villagers and observed that 321 required one additional treatment while 89 villagers required two additional treatments; 24 of the 89 were still not cured after a third dose of this drug. Eggs were isolated from fecal samples and serum was isolated from blood taken from seven villagers successfully treated after a single dose and from 14 villagers not successfully treated after two or three doses of PZQ. The eggs were used to establish infections in mice (isolates), which were then treated six weeks after infection with three different doses of PZQ. Serum was used to determine the concentration of PZQ in the infected humans. Three of the egg isolates from the 14 villagers that could not be treated with three doses of PZQ produced infections in mice that were statistically less responsive to PZQ when compared with isolates obtained from patients that were cured after a single dose of this drug. Pharmacokinetic parameters were the same in patients treated successfully after a single dose versus those not treated successfully following two or three doses, thus eliminating the possibility that poor cure rates among infected villagers was due to a decrease in PZQ bioavailability. From our data, approximately 1-2.4% of the villagers treated with PZQ could not be completely cured of their infection and three of every 1,000 treated villagers may harbor parasites that can tolerate high doses of PZQ. These results indicate that the extensive use of PZQ in the Nile delta region of Egypt has not resulted in a dramatic change in the efficacy of this drug. The isolation of schistosomes that are less susceptible to PZQ may be a warning signal that will require establishment of a monitoring system, similar to the one we have developed, to determine if the percentage of patients that cannot be cured by PZQ is increasing. Furthermore, if that percentage begins to increase over time, it will be critical to determine, by pharmacologic methods reported in this study, whether isolates obtained from uncured patients are becoming increasingly resistant to PZQ.

Adult↗
PubMed1995

Plaque-associated expression of human herpesvirus 6 in multiple sclerosis.

Representational difference analysis was used to search for pathogens in multiple sclerosis brains. We detected a 341-nucleotide fragment that was 99.4% identical to the major DNA binding protein gene of human herpesvirus 6 (HHV-6). Examination of 86 brain specimens by PCR demonstrated that HHV-6 was present in > 70% of MS cases and controls and is thus a commensal virus of the human brain. By DNA sequencing, 36/37 viruses from MS cases and controls were typed as HHV-6 variant B group 2. Other herpesviruses, retroviruses, and measles virus were detected infrequently or not at all. HHV-6 expression was examined by immunocytochemistry with monoclonal antibodies against HHV-6 virion protein 101K and DNA binding protein p41. Nuclear staining of oligodendrocytes was observed in MS cases but not in controls, and in MS cases it was observed around plaques more frequently than in uninvolved white matter. MS cases showed prominent cytoplasmic staining of neurons in gray matter adjacent to plaques, although neurons expressing HHV-6 were also found in certain controls. Since destruction of oligodendrocytes is a hallmark of MS, these studies suggest an association of HHV-6 with the etiology or pathogenesis of MS.

Adult↗
PubMed1995

Ascaris suum: characterization of transmural and hypodermal potentials.

Electrophysiological measurements demonstrate that an electrochemical potential exists across the body wall of parasitic nematodes. The ionic dependence of this transmural electrical potential (Etm) in the gastrointestinal nematode Ascaris suum was investigated using conventional electrophysiological techniques. Etm recorded from intact A. suum maintained in artificial pseudocoelomic fluid (APF) was -40 +/- 12 mV. This potential was more sensitive to external acetate than to Na+, K+, or Cl-, although elimination of most Na+ from the medium significantly hyperpolarized the body wall. An Ussing chamber and isolated segments of A. suum body wall were used to delineate the barrier characteristics of the individual components of the body wall: the cuticle and the inward- and outward-facing membranes of the hypodermis. The cuticle (i.e., muscle and hypodermis scraped away) is highly permeable to both inorganic and organic ions, with the rank-order of permeability among ions tested being K+ > Na+ = Cl- > acetate- > gluconate-. The inward- and outward-facing membranes of the hypodermis were more polarized than the body wall complex, exhibiting potentials in APF of -47.6 +/- 6 mV (Ei) and -74.9 +/- 7 mV (Eo) versus -26 +/- 8 mV (Etm for isolated body wall segments), respectively. The electrical potential across the hypodermal membranes became depolarized when high K+ medium or low acetate medium was added to the muscle side, but not when added to the cuticle side of isolated body wall segments. Etm, Eo, and Ei were unaffected by reduction of Na+, K+, or Cl- concentrations in the recording medium. All three potentials, however, became markedly depolarized when the temperature of the incubation medium was reduced. These results indicate that the cuticle/hypodermis complex of A. suum is differentially permeable to both inorganic and organic ions and suggest that active transport of ions or outward diffusion of metabolic end-products contributes extensively to the maintenance of transmural electrochemical gradients.

Animals↗
PubMed1995

Immunohistochemical localization of a Shaker-related voltage-gated potassium channel protein in Schistosoma mansoni (Trematoda: Digenea).

We have recently isolated a cDNA (SKv1.1) encoding a Shaker-related K+ channel from the human parasitic trematode Schistosoma mansoni. In order to better understand the functions of SKv1.1 protein, the distribution of SKv1.1 protein in adult S. mansoni was analyzed by immunohistochemistry using a region-specific antibody. SKv1.1 proteins were widely expressed in the nervous and muscular systems. The strongest immunoreactivity (IR) was observed in the nervous system of both male and female. In the nervous system, IR for SKv1.1 proteins was localized in cell bodies and nerve fibers of the anterior ganglia, the central commissure, and the main nerve cords. IR was also observed in the dorsal and the ventral peripheral nerve nets, fine nerve fibers entering into a variety of structures such as the dorsal tubercles, longitudinal and ventral muscle fibers, and oral and ventral suckers. In the muscular system, SKv1.1 proteins were localized to the longitudinal, circular, and ventral muscle fibers of male as well as in isolated muscle fibers where native A-type K+ currents were measured. Moderate IR was also seen in a large number of cell bodies in the parenchyma. These results indicate that SKv1.1 protein may play an important role in the regulation of the excitability of neurons and muscle cells of S. mansoni.

Amino Acid Sequence↗
PubMed1995

Analysis of the kinetics and voltage-dependency of transient and delayed K+ currents in muscle fibers isolated from the flatworm Schistosoma mansoni.

There are two distinct voltage-dependent K+ currents in muscle fibers freshly isolated from the human flatworm parasite S. mansoni. Present is a delayed rectifier current with a tau act of 17 msec and tau inact > 3 sec. The delayed rectifier is very resistant to steady-state inactivation, with over 40% of the current non-inactivating, and over 15 sec required for the maximum inactivation of the other portion. The current is resistant to block by extracellular tetraethylammonium, is half-blocked by 10 mM 4-aminopyridine, and is insensitive to dendrotoxin. Also present is an "A" current with tau act < 1 msec and tau inact < 15 msec. The "A" current, like the delayed rectifier current, is resistant to block by external tetraethylammonium and is insensitive to dendrotoxin. Three micromoles of 4-aminopyridine produce a half-blockade of the "A" current. These two K+ currents are very similar to a delayed rectifier and "A" currents that have been described in a number of lower and more advanced animals.

4-Aminopyridine↗
PubMed1995

Cloning and functional expression of a Shaker-related voltage-gated potassium channel gene from Schistosoma mansoni (Trematoda: Digenea).

We have isolated a cDNA (SKv1.1) encoding a Shaker-related K+ channel from an adult cDNA library of the human parasitic trematode Schistosoma mansoni. The deduced amino acid sequence (512 aa, 56.5 kDa) contains 6 putative membrane-spanning domains (S1-S6) and a pore-forming domain (H5). SKv1.1 is grouped in the Shaker family, but forms a unique branch within this family, on the basis of dendrogram analysis. SKv1.1 shows significant sequence identity with most other Shaker channels, with 64-74% identity in the core region (S1-S6). It has the highest sequence identity with the K+ channel (Ak01a) from Aplysia. Northern blot analysis detected a single primary transcript of 2.8 kb. Southern blot analysis indicated that SKv1.1 is present as a single copy in the genomic DNA of S. mansoni. Expression of SKv1.1 in Xenopus oocytes produced a rapidly activating and inactivating outward K+ current which is highly sensitive to 4-aminopyridine, but is insensitive to tetraethylammonium, mast cell degranulating peptide, dendrotoxin and charybdotoxin. The presence of a Shaker homologue in Schistosoma suggests that Sh subfamilies may exist in other lower invertebrates as well as platyhelminths.

Amino Acid Sequence↗
PubMed1995

A preliminary investigation of postmortem tooth loss.

Forensic anthropologists have found a seemingly increased frequency of dismemberment cases and subsequent scattering of the elements that mandates developing unconventional methods of estimating postmortem interval. The chronological sequence in postmortem tooth loss has been investigated as an indicator for estimation of time since death. The anterior dentitions of cadavera were observed to discern patterns in "drop time" based on age, periodontal health, seasonality and location of body placement. Individuals deposited in the summer months lost teeth much more rapidly than those deposited in the late fall or winter months. Similarly, individuals exposed to direct sunlight, a micro-environment where rapid decomposition has been noted, lost teeth before individuals in shaded locales. Since tooth loss is dependent on the deterioration of the soft tissues which bind the tooth into the alveolar bone, we found tooth loss to be correlated with general soft tissue decomposition rates as dictated by season and environment. When utilized as sole indicator, the patterns of postmortem tooth loss can not be used for estimating time since death. However, when used in conjunction with other indicators, tooth loss patterns may provide useful information for more accurate estimation of the postmortem interval.

Adult↗
PubMed1995

Effect of cimetidine, bicarbonate and glucose on the bioavailability of different formulations of praziquantel.

The effects of cimetidine, bicarbonate and glucose on the bioavailability of the two brands of praziquantel (CAS 55268-74-1) available in Egypt were studied in normal healthy volunteers. Brand 1 when coadministered with cimetidine showed elevated concentration of the drug at all time intervals. The difference was statistically significant at 3, 4, 6 and 8 h following treatment. On the other hand coadministration of cimetidine with brand 2 (Distocide) showed elevated concentration of the drug 1 h post treatment. Analysis of the pharmacokinetic parameters revealed insignificant difference comparing brand 1 versus brand 1 plus cimetidine. Significant differences were observed between the elimination rate constant Ke (h-1) for brand 2 (0.017 +/- 0.004) alone versus brand 2 plus cimetidine (0.006 +/- 0.001). Coadministration of bicarbonate or glucose with either brand 2 or brand 1 tended to depress the serum concentration of praziquantel. Possible explanations of these findings are discussed.

Adolescent↗