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Biomedical subjects

F J Thompson

Publications and source records attributed to F J Thompson.

At least 19 recordsLinked to original sources
PubMed2005

TGF-beta and the evolution of nematode parasitism.

The many similarities between arrested dauer larvae of free-living nematodes and infective L3 of parasitic nematodes has led to suggestions that they are analogous lifecycle stages. The control of the formation of dauer larvae in Caenorhabditis elegans is well understood, with a TGF-beta-superfamily growth factor playing a central role. Recent analyses of the expression of homologous TGF-beta genes in parasitic nematodes has allowed this analogy to be tested; but the results so far do not support it. Rather, the results imply that in the evolution of animal parasitism, parasitic nematodes have taken signalling pathways and molecules from their free-living ancestors and used them in different ways in the evolution of their parasitic lifestyles.

Animals↗
PubMed2004

The effect of the host immune response on the parasitic nematode Strongyloides ratti.

The host immune response has profound effects on parasitic nematode infections. Here we have investigated how a range of infection parameters are affected by host immune responses and by their suppression and enhancement. The infection parameters considered were the number of parasitic females, their size, per capita fecundity and intestinal position. We found that in immunosuppressive treatments worms persist in the gut, sometimes with a greater per capita fecundity, maintain their size and have a more anterior gut position, compared with worms from control animals. In immunization treatments there are fewer worms in the gut, sometimes with a lower per capita fecundity and they are shorter and have a more posterior gut position, compared with worms from control animals. Worms from animals immunosuppressed by corticosteroid treatment reverse their changes in size and gut position. This description of these phenomena pave the way for a molecular biological analysis of how these changes in infection parameters are brought about by the host immune response.

Animals↗
PubMed2001

Temperature is a cue for gene expression in the post-infective L3 of the parasitic nematode Brugia pahangi.

The temporal expression pattern of two genes, Bp-cdd and Bp-S3, was studied at defined points throughout the life cycle of Brugia pahangi. Both mRNAs were up-regulated to coincide with the transition of the L3 from the vector to the mammalian host. Bp-cdd was expressed almost exclusively in the post-infective (p.i.) L3 and L4 stages of the life cycle while Bp-S3 was also expressed in adult worms, but at a much lower level than in the larval stages. Immunogold labelling with an antiserum raised to the recombinant Bp-CDD localised the native antigen to the hypodermis in the p.i. L3 and L4. Specific labelling was not detected in the adult worm. The expression of both mRNAs could be triggered by exposure of the vector-derived L3 to a simple mammalian culture system. Analysis of the factors, which induced expression suggested that the temperature shift which accompanies the transition from mosquito to mammal was the most important cue for expression of both genes.

Animals↗
PubMed2001

Heat shock and developmental expression of hsp83 in the filarial nematode Brugia pahangi.

hsp83 was cloned from the filarial nematode Brugia pahangi. The mRNA was constitutively expressed at 37 degrees C in life cycle stages that live in the mammalian host (microfilariae and adult worms). Heat shock resulted in only a minimal increase in levels of transcription. A genomic copy of hsp83 was isolated and was shown to contain 11 introns while sequencing of the 5' upstream region revealed several heat shock elements. Using a chloramphenicol acetyltransferase (CAT) reporter gene construct the expression of hsp83 from B. pahangi (Bp-hsp83) was studied by transfection of COS-7 cells. Similar to the expression pattern in the parasite, CAT activity was detected at 37 degrees C and was not influenced by heat shock. When the free-living nematode Caenorhabditis elegans was transfected with the same construct, CAT activity was not observed at normal growth temperatures (21 degrees C) or under moderate heat shock conditions (28 degrees C). However exposure to more severe heat shock (35 degrees C) resulted in an increase in CAT activity. These results suggest that Bp-hsp83 has a temperature threshold > or = 35 degrees C for expression.

Animals↗
PubMed2001

Acute effects of locomotor training on overground walking speed and H-reflex modulation in individuals with incomplete spinal cord injury.

OBJECTIVE: The purpose of this study was to assess the effect of a single bout of a locomotor-training paradigm on overground walking speed and H-reflex modulation of individuals with incomplete spinal cord injury (SCI). METHODS: Self-selected and maximum walking speeds and soleus H-reflexes (H/M ratios) during standing and stance and swing phases of walking (self-selected velocity) were obtained from 4 individuals with American Spinal Injury Association impairment classification D. Data were collected immediately before and after a single bout of locomotor training with body weight support on a treadmill. The pretraining H/M ratios of the SCI subjects were also compared with values from 4 able-bodied subjects who did not receive the intervention. Maximum H/M ratios while standing and during midstance and midswing phases of overground walking were considerably greater in the SCI subjects than in the control subjects. RESULTS: After the single bout of training, self-selected and maximum overground walking speeds of the subjects with SCI increased by 26% and 25%, respectively. Furthermore, H-reflexes were significantly more depressed in the SCI subjects during overground walking (28% less during stance, 34% less during swing). CONCLUSIONS: Although preliminary, these findings indicate that a single bout of locomotor training produced immediate increases in walking velocity and acute neurophysiologic changes in individuals with incomplete SCI.

Adolescent↗
PubMed2001

Feasibility and safety of neural tissue transplantation in patients with syringomyelia.

Transplantation of fetal spinal cord (FSC) tissue has demonstrated significant potential in animal models for achieving partial anatomical and functional restoration following spinal cord injury (SCI). To determine whether this strategy can eventually be translated to humans with SCI, a pilot safety and feasibility study was initiated in patients with progressive posttraumatic syringomyelia (PPTS). A total of eight patients with PPTS have been enrolled to date, and this report presents findings for the first two patients through 18 months postoperative. The study design included detailed assessments of each subject at multiple pre- and postoperative time points. Outcome data were then compared with each subject's own baseline. The surgical protocol included detethering, cyst drainage, and implantation of 6-9-week postconception human FSC tissue. Immunosuppression with cyclosporine was initiated a few days prior to surgery and continued for 6 months postoperatively. Key outcome measures included: serial magnetic resonance imaging (MRI) exams, standardized measures of neurological impairment and functional disability, detailed pain assessment, and extensive neurophysiological testing. Through 18 months, the first two patients have been stable neurologically and the MRIs have shown evidence of solid tissue at the graft sites, without evidence of donor tissue overgrowth. Although it is still too soon to draw any firm conclusions, the findings from the initial two patients in this study suggest that intraspinal grafting of human FSC tissue is both feasible and safe.

Adult↗
PubMed2001

Neurophysiological assessment of the feasibility and safety of neural tissue transplantation in patients with syringomyelia.

The feasibility and safety of a procedure involving fetal spinal cord tissue transplantation in patients with syringomyelia was assessed using a neurophysiological protocol designed to quantitate peripheral nerve function, spinal cord reflex excitability, and spinal cord conduction pathways essential for somatosensory evoked potentials. We report here data obtained before and for 18 months following the transplantation procedure performed on the first two patients in this study. The neurophysiological assessment protocols included measures of cortical and spinal cord evoked potentials, H-reflex excitability, and peripheral nerve conduction. Prior to the procedure, both patients had significant deficits on some of the neurophysiological measures, for example, lower extremity cortical evoked potentials. However, robust measures of intact pathways, such as upper extremity cortical evoked potentials, were also observed preoperatively in both patients. Thus, it was anticipated that conduction in these intact pathways could be at risk either from complications from the transplantation procedure and/or from continued expansion of the syrinx. Following the transplantation procedure, no negative changes were observed in any of the neurophysiological measures in either patient. In addition, patient 1 showed a decrease in the rate potentiation of tibial H-reflexes on the right side and an increase in the response probability of left tibial H-reflexes. The results of this postoperative longitudinal assessment provide a first-level demonstration of the safety of the intraspinal neural tissue transplantation procedure. However, the consideration of safety is currently limited to the grafting procedure itself, since the long-term fates of the donor tissue in these two patients remain to be shown more definitively.

Action Potentials↗
PubMed2001

Scientific basis of spasticity: insights from a laboratory model.

A variety of central nervous system injuries, diseases, and developmental deficits can lead to motor disorders that present complex mixtures of symptoms. Those that have a fundamental similarity characterized by the appearance of exaggerated velocity-dependent resistance to the lengthening of skeletal muscles are called spasticity. Reports based on clinical observations of motor disorders have and continue to provide the essential database of information regarding the range and distribution of unifying and discordant features of spasticity. Laboratory investigations employing animal models of motor disorders following experimental lesions of the central nervous system have reproduced some of the neurophysiologic changes that accompany injury of the central nervous system in humans. Those experimental lesions produced by spinal cord contusion/compression reproduce many of the histopathologic features displayed in traumatic injury of the human spinal cord as well. Studies using this model have revealed not only changes in reflex threshold and amplitude but also alterations in fundamental rate-modulation processes that regulate reflex excitability during repetitive stimulation. This report characterizes insights obtained from a laboratory investigation in search of fundamental mechanisms that contribute to the development of spasticity and provides a vantage point for understanding therapeutic strategies for treatment of spasticity.

Animals↗
PubMed2000

Modulation of triceps surae H-reflexes as a function of the reflex activation history during standing and stepping.

The facilitatory effectiveness of spindle afferent feedback is controlled by modulation of segmental reflex excitability such that the level of muscle activation is appropriate for the task. Phase-dependent modes of reflex modulation have been well-characterized. We hypothesized that segmental reflex excitability of the triceps surae was also modulated in a manner associated with the activation history of the spindle afferents and the segmental reflex pathway during isometric contractions, standing and stepping. In the first experiment. pairs of soleus (S) H-reflexes were evoked 80 ms apart with equal strength stimuli at rest and while subjects isometrically contracted their S against loads of 10%. 20%. and 50% of their maximum voluntary efforts. The percent depression of the second H-reflex relative to the first was used as a measure of the effect of reflex activation history. At rest, the second H-reflexes were depressed an average of 73% relative to the first. The degree of depression was progressively reduced as the plantarflexion torque increased. In the second experiment, paired H-reflexes were obtained from the S and medial (MG) and lateral gastrocnemii (LG) muscles while subjects were standing and during the stance phase of step initiation. The degree of depression of the second H-reflex during standing ( > 78%) was similar in magnitude to that produced at rest in Experiment I. At the end of the stance phase of stepping. depression of the second H-reflex of all three muscles was reduced to less than 25%. We conclude that the segmental reflex excitability is modulated as a function of the reflex activation history during these tasks.

Adult↗
PubMed1999

The isolation of differentially expressed cDNA clones from the filarial nematode Brugia pahangi.

A cDNA library constructed from 3 day post-infective L3 of the filarial nematode Brugia pahangi was screened by differential hybridization with cDNA probes prepared from different life-cycle stages. Five cDNA clones hybridizing selectively to the mosquito-derived L3 probe were isolated and characterized. Northern blot analysis of 4 of the clones confirmed that each was most highly expressed in the mosquito-derived L3. The expression of each mRNA during parasite development in the mosquito vector was investigated using RT-PCR, and all were shown to be abundant in the immature L3. Four of the 5 cDNAs cloned coded for structural proteins: 2 cuticular collagens, and the muscle proteins tropomyosin and troponin. Further studies on troponin using an antiserum raised to the recombinant protein demonstrated that the protein, unlike the mRNA, was present in all life-cycle stages examined, while immunogold labelling demonstrated that it was localized to the muscle blocks.

Animals↗
PubMed1998

Alteration in rate modulation of reflexes to lumbar motoneurons after midthoracic spinal cord injury in the rat. I. Contusion injury.

This study investigated the regulation of reflex excitability in normal and midthoracic contusion-injured animals. Recent observations revealed that rate depression, a rate-modulatory process that decreases reflex excitability, was significantly decreased following experimental midthoracic contusion injury. The present experiments were performed to extend those studies and to determine if posttetanic potentiation (PTP), a rate-modulatory process that increases reflex excitability, also was altered in lumbar monosynaptic reflexes (MSRs) following midthoracic contusion injury. In normal animals, a mean PTP of 160% of the pretetanus control was observed at 30 sec following tetanus of the tibial MSR. The decay of the PTP in normal animals followed a rapid initial, then a more gradual pattern, before returning to pretetanus values by 5 min posttetanus. Following midthoracic contusion injury, the maximal (unpotentiated) MSRs were significantly increased in amplitude, whereas the percent potentiation of the PTP of the tibial MSRs was significantly decreased. PTP decay in postcontusion animals was significantly more gradual than observed in normal animals and followed a single decay process. Further analysis of rate depression of tibial MSRs in normal animals revealed that the attenuation pattern produced by stimulation within the lower range of test frequencies was different from that produced by stimulation at the higher test frequencies. Following contusion, rate depression of tibial MSRs was significantly reduced at all test frequencies. These physiological changes in the stretch reflex neural pathway are discussed relative to the development of spasticity.

Animals↗
PubMed1996

Velocity-dependent ankle torque in the normal rat.

We evaluated the velocity-dependent ankle torque and associated activity of the ankle extensor muscle stretch reflexes in normal rats. A 287% increase in velocity-dependent ankle torque was observed at the highest velocity tested compared with the lowest velocity. Low velocity torques were minimally altered during general anesthesia that depressed EMG activity by up to 90%. However, velocity-dependent torque during higher velocity ankle rotations (306-612 degrees s-1 correlated with parallel increases in EMG magnitude recorded from the triceps surae muscles. General anesthesia (pentobarbital) abolished 61% of the velocity-dependent ankle torque at 612 degrees s-1. We conclude that ankle torque and ankle extensor muscle activity display velocity enhancement over a broad range. These observations indicate that protocols designed to assess ankle torque in the rat should use instrumentation to produce a broad range of velocities up to at least 600 degrees s-1.

Anesthesia, General↗
PubMed1996

Influence of ORF2 on host cell tropism of feline immunodeficiency virus.

Feline immunodeficiency virus (FIV) is a lentivirus associated with an immunodeficiency syndrome of the domestic cat. A short open reading frame (ORF2), of unknown function, is present in all FIV isolates. We have investigated the role of ORF2 in determining the cell tropism of two infectious molecular clones of FIV. FIV-PPR is able to productively infect feline peripheral blood leukocytes (PBLs) and a T lymphocyte cell line (MCH5-4), but not a feline astrocyte cell line (G355-5) or Crandell feline kidney cells (CrFK). In contrast, FIV-34TF10 is able to productively infect G355-5 and CrFK cells, but not PBLs or MCH5-4 cells. The major difference in these FIV clones is that ORF2 in FIV-PPR is capable of encoding a 79-amino-acid peptide, whereas there is a stop codon in ORF2 after 43 amino acids in FIV-34TF10. We performed site-directed mutagenesis to change the stop codon (TGA) in FIV-34TF10 to a tryptophan (TGG), the amino acid present at this location in FIV-PPR. FIV-34TF10 with ORF2 repaired (FIV-ORF2rep) productively infected PBLs, MCH5-4 cells, and primary macrophages, as well as CrFK and G355-5 cells, indicating that a protein encoded by ORF2 plays a role in determining the host cell tropism of FIV. ORF2 contains hydrophobic, acidic, and leucine-rich domains similar to those shown to be important for transactivating proteins of other lentiviruses. Coexpression of a plasmid expressing the ORF2 gene product with another construct expressing the chloramphenicol acetyl transferase (CAT) gene driven by the FIV LTR, resulted in transactivation of CAT expression in both feline and human cells.

Amino Acid Sequence↗
PubMed1996

Brugia pahangi: characterisation of a small heat shock protein cDNA clone.

Microfilariae of Brugia pahangi undergo a transition in their life cycle from the homeothermic mammalian host to the poikilothermic mosquito vector. Coincident with this switch, the developmental cycle of the microfilaria is reinitiated. When cultured at mammalian temperatures (37 degrees C), microfilariae express a complex of small heat shock proteins. In order to further characterise this group of proteins a cDNA library was constructed from heat-shocked microfilariae by reverse-transcriptase PCR and then screened with a heterologous probe. A clone which codes for a small heat shock protein was isolated and characterised in detail. Southern blot analysis identified a putative small heat shock protein multigene family. The expression of the small heat shock protein cDNA appears to be controlled at the level of RNA synthesis and is highly stage specific and temperature dependent.

Amino Acid Sequence↗
PubMed1996

Stage-specific gene expression in lymphatic filarial nematodes.

Lymphatic filarial nematodes remain a significant cause of morbidity throughout much of the tropics. One approach to the development of rational control methods is an improved understanding of the basic biology of these organisms in relation to the mechanisms used to complete their life cycles. In this article, Eileen Devaney, Sam Martin and Fiona Thompson review new approaches to defining stage-specific molecules in filarial nematodes, and discuss their recent work on the isolation and characterization of stage-regulated cDNAs from Brugia pahangi.

Journal Article↗