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J Thompson

Publications and source records attributed to J Thompson.

At least 73 records · Page 4Linked to original sources
PubMed2001

Comparative genomics in Plasmodium: a tool for the identification of genes and functional analysis.

Comparative genomics allows inferences to be drawn about the coding potential of related genomes, and the evolutionary forces that have influenced genome organisation. Early comparisons have indicated that there is significant synteny (conserved physical association of genes) between the human parasite Plasmodium falciparum and the malaria parasites of rodents, such as Plasmodium berghei. The various Plasmodium genome initiatives have now provided the opportunity to perform comparative genomics within different species of malaria parasites in more detail, allowing the discovery of orthologues and paralogues of less well conserved genes and addressing questions of conservation, evolution and structure of multi-gene families. A remarkable level of conservation is being revealed, illustrated here by a comparison of members of one of the first conserved gene families to emerge from the sequencing initiatives, the P48/45 gene family. We have identified two additional members in this family, Pf36p and Pfs38, and shown that all members are conserved in P. falciparum and P. berghei, opening the way for functional analyses in the latter more accessible rodent malaria model. In addition, it has been shown that direct comparison of a 13.6 kb contig of a chromosome of P. berghei and the orthologous region in P. falciparum reveals an unexpected high level of conservation of gene organisation and complexity. The results of this comparison highlight the value of a comparative approach to elucidate the gene content of complex loci and improve its annotation

Amino Acid Sequence↗
PubMed2001

Longitudinal evaluation of cognitive disorder in Huntington's disease.

The study investigated longitudinal change in cognitive function in 87 patients with Huntington's disease (HD), using a range of neuropsychological tests, which tap mental manipulative abilities, memory, and frontal executive skills. Over a 1-year period the largest changes were noted in letter fluency, object recall, and Stroop Test performance, whereas no changes were noted over more than 3 years on the modified Wisconsin Card Sorting Test. Contrary to expectation, greater change was evident over 1 year for tasks with low compared to high cognitive demands. The differential sensitivity of tasks was attributed in part to inherent characteristics of the tests themselves: their capacity to detect minor gradations of change and their vulnerability to practice effects. However, the greater change for relatively automatic, speed-based tasks with low cognitive demands was interpreted as reflecting the evolution of HD, with a greater magnitude of change occurring in basal ganglia than cortical function. One purpose of the study was to identify tasks sensitive to the progression of HD and hence most suitable for the evaluation of therapies. Despite reaching statistical significance by virtue of the large group size, numerical differences in test scores over 1 year were very small, suggesting that the use of such tests to evaluate change in individuals or small groups of subjects would be problematic. The data highlight the slow progression of HD, the limitations of standard cognitive tests in detecting change over short periods, and the need for therapeutic studies that encompass a relatively prolonged time frame.

Adult↗
PubMed2001

Staphylococcus aureus domain V functions in Escherichia coli ribosomes provided a conserved interaction with domain IV is restored.

Domain V of Escherichia coli 23 S rRNA (residues 2023-2630) was replaced by that from Staphylococcus aureus, thereby introducing 132 changes in the rRNA sequence. The resulting ribosomal mutant was unable to support cell growth. The mutant was rescued, however, by restoring an interaction between domains IV and V (residues 1782 and 2586). Although the importance of this interaction, U/U in E. coli, C/C in S. aureus, is therefore demonstrated, it cannot be the only tertiary interaction important for ribosomal function as the rescued hybrid grew more slowly than the wild type. Additionally, although the single-site mutations U1782C and U2586C in E. coli are viable, the double mutant is lethal.

Base Sequence↗
PubMed2001

Immunohistochemical detection of ornithine-decarboxylase in primary and metastatic human breast cancer specimens.

Increased ornithine decarboxylase (ODC) activity in human breast cancer specimens has recently been shown to be an independent adverse prognostic factor for recurrence and death. Biochemical measurement of ODC, however, is not practical for routine clinical use. Furthermore, it does not take into account the heterogeneous composition of human breast cancers which contain variable proportions of epithelial and stromal elements. Therefore, we developed an immunohistochemical method for ODC determination which can be applied to formalin-fixed, paraffin-embedded tissue sections. We report here our results in a series of 30 human breast cancer samples. ODC expression was detected most consistently in the malignant epithelial component of the tumors. Twenty-seven of 30 samples stained positive with intensities ranging from 1+ to 3+. The fraction of malignant epithelial cells expressing ODC varied among specimens between 10% and > 90%. When quantitated by H-SCORE, ODC expression was significantly higher in the malignant epithelial component than in normal appearing epithelial cells and stroma admixed within the tumor. Normal mammary tissue adjacent to the cancer was available for analysis in six cases. ODC expression was absent in two (while both cancers were positive) but present in four to a degree which was overall comparable to that observed in the corresponding tumors. We believe that this technique will be useful for future studies aimed at expanding our knowledge of the role of ODC and polyamines (PA) in breast cancer biology.

Adult↗
PubMed2001

Pre-emptive metoclopramide and ondansetron for nausea and vomiting associated with iloprost infusions.

OBJECTIVE: To assess the effectiveness of ondansetron in relieving symptoms of nausea and vomiting which were refractory to metoclopramide and cyclizine, in a patient receiving iloprost infusions. METHOD: Case observation in a series of 7 infusions. RESULTS: Ondansetron reduced WHO symptom scores of vomiting from Grade 2 to Grade 0. Symptoms of nausea were abolished on some occasions. CONCLUSION: Ondansetron was found to be effective at abolishing symptoms of vomiting and partially effective against symptoms of nausea. It may prove to be a useful treatment modality to allow the patient to tolerate further infusions of iloprost where nausea and vomiting has failed to respond to other agents.

Aged↗
PubMed2001

Antimicrobial activity of ergokonin A from Trichoderma longibrachiatum.

AIMS: Natural fungal products were screened for antifungal compounds. The mode of action of one of the hits found and the taxonomy of the producing organism were analysed. METHODS AND RESULTS: An extract from a Trichoderma species showed a more potent activity in an agar-based assay against the null mutant fks1::HIS strain than against the wild-type strain, suggesting that it could contain a glucan synthesis inhibitor. The active component was identified as the known compound ergokonin A. The compound exhibited activity against Candida and Aspergillus species, but was inactive against Cryptococcus species. It induced alterations in the hyphal morphology of Aspergillus fumigatus. The identification of the producing isolate was confirmed by sequencing of the rDNA internal transcribed spacers and comparison with the sequences of other Trichoderma species. The analysis showed that the producing fungus had a high homology with other strains classified as Trichoderma longibrachiatum and its teleomorph Hypocrea schweinitzii. CONCLUSIONS: The antifungal activity spectrum of ergokonin A and the morphology alterations induced on A. fumigatus are consistent with glucan synthesis as the target for ergokonin A. The production of ergokonin A is not uncommon, but is probably restricted to Trichoderma species. SIGNIFICANCE AND IMPACT OF THE STUDY: The discovery that ergokonin A could be an inhibitor of glucan synthesis, having a structure very different to other inhibitors, increases the likelihood that orally active agents with this fungal-specific mode of action may be developed.

Animals↗
PubMed2001

Vagus nerve stimulation: analysis of device parameters in 154 patients during the long-term XE5 study.

PURPOSE: To determine the effect of changes in device settings and duty cycle (on and off times) on the efficacy of vagus nerve stimulation (VNS) for refractory epilepsy. In the long-term XE5 study of VNS for intractable epilepsy, the median reduction in seizure frequency improved significantly after 1 year of follow-up. A central question is whether device changes improve efficacy. We analyzed the effects of device parameter changes on seizure frequency in 154 subjects who completed the study and who had complete data for analysis. METHODS: Retrospective analysis of device changes during the XE5 long-term study of VNS. During the XE5 long-term follow-up study, the subject's device settings were modified within a Food and Drug Administration (FDA)-approved range of output current, pulse duration, frequency, on time, and off time. Significant changes in device settings occurred after 3 months. We investigated the relationship between percentage reduction in seizures and changes in device parameters between the 3- and 12-month visits. Within-group comparisons were performed for those who continued on standard on/off cycle of 30 s on and 5 min off, and those with the most common off times of 3, 1.8, and < 1.1 min. RESULTS: Output current, pulse duration, frequency, and off time changed significantly between the 3- and 12-month long-term follow-ups. For the group as a whole, changes in device settings were not correlated with an improvement in efficacy. However, a significant improvement in efficacy occurred in a subgroup whose off time was reduced to < or = 1.1 min. In this group, the median reduction in seizures improved from 21% before the change in off time, to 39% after the change in off time (Wilcoxon Signed-Rank, p = 0.011). The responder rate (> 50% reduction in seizures) also significantly improved from 19 to 35% (McNemar's test, p = 0.046). CONCLUSIONS: The data from this retrospective analysis indicate that device changes were not the primary determinant of increased efficacy at 12 months of long-term follow-up. In general, patients who remained on the original settings of 30 s on and 5 min off continued to respond or improve in their response over the 1-year period. However, some patients may benefit from reductions in off time (increases in duty cycle). In a subgroup initially resistant to VNS, a change in off time to < or = 1.1 min off did result in significant improvements in efficacy.

Double-Blind Method↗
PubMed2001

Combination of interferon and ribavirin in chronic hepatitis C: re-treatment of nonresponders to interferon.

Chronic infection with hepatitis C virus (HCV) may result in cirrhosis, liver failure, and hepatocellular carcinoma. A minority of patients have a sustained response to antiviral therapy, and nonresponders remain at risk of developing progressive liver disease. We conducted a randomized, controlled trial of therapy with the combination of interferon (IFN) and ribavirin in patients with chronic hepatitis C who had not responded to an initial course of therapy with IFN alone. A total of 124 patients were randomized to receive the combination of IFN and ribavirin for either 24 or 48 weeks and followed for an additional 24 weeks after stopping therapy. Thirty-eight treated patients (30.6%) achieved a sustained virologic response (undetectable HCV RNA at the 24-week follow-up point). This was associated with significant improvement in necroinflammatory activity noted on liver biopsy. Interestingly, there was not a statistically significant difference in response rates based on the duration of treatment; HCV genotype was the strongest predictor of a sustained response. Sustained responses were noted even in patients with poor predictive factors, including those with advanced hepatic fibrosis or cirrhosis, high levels of HCV RNA in serum, and those infected with HCV genotype 1. The study included 24 patients with normal serum alanine transaminase (ALT) values before therapy who had similar responses to those with initially elevated transaminase values. This study suggests that the combination of IFN and ribavirin is a useful modality of therapy in patients with chronic hepatitis C who did not respond to IFN alone.

Adult↗
PubMed2001

Prevalence of HIV-1 and oral lesions in pregnant women in rural Malawi.

OBJECTIVE: Whether oral lesions were associated with human immunodeficiency virus-type 1 (HIV-1) status in a cohort of pregnant Malawian women was studied. STUDY DESIGN: Six hundred thirty-eight women participated in a randomized prospective study at 3 prenatal clinics in a rural area of southern Malawi. Oral examinations, followed by collection of oral fluid specimens with an HIV-1 oral specimen collection device, were performed. The specimens were tested for antibodies against HIV-1. RESULTS: Sixty-one oral lesions were found in 60 participants. While traditional HIV-1 associated lesions were rare, benign migratory glossitis was unexpectedly common (6%). Oral hairy leukoplakia was significantly more common among women who were HIV-1 positive than among women who were HIV-1 negative. An HIV-1 prevalence rate of 21.8% was estimated among the women, with the highest rate of HIV-1 infection (34.1%) among women aged 25 to 29 years. CONCLUSION: Stratifying lesions showed a small number of oral hairy leukoplakia to be markers for HIV-1. A high seroprevalence was found in this rural cohort, but there were unexpectedly few oral lesions. The relatively few oral lesions diagnosed may indicate a recent infection with HIV.

Adult↗
PubMed2001

Evaluation of a predictive model for implant surface topography effects on early osseointegration in the rat tibia model.

STATEMENT OF PROBLEM: Alterations in commercially pure titanium (cp Ti) implant surface topography can be made to increase bone formation or the interfacial shear strength of bone at the functioning implant. It is not known whether these 2 goals are congruent or mutually exclusive. PURPOSE: The aim of this study was to determine the effect of implant surface topography parameters of calculated biomechanical significance on the process of bone formation in a rat tibia model of osseointegration. MATERIAL AND METHODS: Implants (cp Ti grade IV) were machined and subsequently treated by grit blasting or grit blasting and 6.4 mol/L HCl. Measurements of surface roughness were made by atomic force microscopic analysis of similarly treated titanium disks. Cleaned and sterilized implants (12 machined, 12 with nonideal pit morphology, 12 with ideal pit morphology) were placed into the tibiae of 400-g male Wistar rats by using a series of drills, irrigation, and a self-tapping procedure. After 3 weeks, tibiae were harvested and processed and embedded in methyl methacrylate resin. Polished sections were examined by backscatter electron microscopy, and the percentage implant surface contacting bone was measured with the Scionics PC image analysis program. RESULTS. The implants possessing a proposed ideal pit morphology supported significantly greater bone formation at the implant surface (54% +/- 7% bone-to-implant contact [P<.003]) than the nonideal pit morphology (40% +/- 15%) or machined surfaces (34% +/- 6%). CONCLUSION: Implant surfaces with a proposed ideal pit morphology (which possess a calculated biomechanical significance) enhanced bone formation at early periods after placement in the rat tibia model.

Animals↗
PubMed2001

Affinity and location of an internal K+ ion binding site in shaker K channels.

We have examined the interaction between TEA and K+ ions in the pore of Shaker potassium channels. We found that the ability of external TEA to antagonize block of Shaker channels by internal TEA depended on internal K+ ions. In contrast, this antagonism was independent of external K+ concentrations between 0.2 and 40 mM. The external TEA antagonism of internal TEA block increased linearly with the concentration of internal K+ ions. In addition, block by external TEA was significantly enhanced by increases in the internal K+ concentration. These results suggested that external TEA ions do not directly antagonize internal TEA, but rather promote increased occupancy of an internal K+ site by inhibiting the emptying of that site to the external side of the pore. We found this mechanism to be quantitatively consistent with the results and revealed an intrinsic affinity of the site for K+ ions near 65 mM located approximately 7% into the membrane electric field from the internal end of the pore. We also found that the voltage dependence of block by internal TEA was influenced by internal K+ ions. The TEA site (at 0 internal K+) appeared to sense approximately 5% of the field from the internal end of the pore (essentially colocalized with the internal K+ site). These results lead to a refined picture of the number and location of ion binding sites at the inner end of the pore in Shaker K channels.

Animals↗
PubMed2001

Improved binding of a bivalent single-chain immunotoxin results in increased efficacy for in vivo T-cell depletion.

Anti-CD3 immunotoxins exhibit considerable promise for the induction of transplantation tolerance in pre-clinical large animal models. Recently an anti-human anti-CD3epsilon single-chain immunotoxin based on truncated diphtheria toxin has been described that can be expressed in CHO cells that have been mutated to diphtheria toxin resistance. After the two toxin glycosylation sites were removed, the bioactivity of the expressed immunotoxin was nearly equal to that of the chemically conjugated immunotoxin. This immunotoxin, A-dmDT390-sFv, contains diphtheria toxin to residue 390 at the N-terminus followed by VL and VH domains of antibody UCHT1 linked by a (G(4)S)(3) spacer (sFv). Surprisingly, we now report that this immunotoxin is severely compromised in its binding affinity toward CD3(+) cells as compared with the intact parental UCHT1 antibody, the UCHT1 Fab fragment or the engineered UCHT1 sFv domain alone. Binding was increased 7-fold by adding an additional identical sFv domain to the immunotoxin generating a divalent construct, A-dmDT390-bisFv (G(4)S). In vitro potency increased 10-fold over the chemically conjugated immunotoxin, UCHT1-CRM9 and the monovalent A-dmDT390-sFv. The in vivo potency of the genetically engineered immunotoxins was assayed in the transgenic heterozygote mouse, tgepsilon 600, in which the T-cells express human CD3epsilon as well as murine CD3epsilon. T-cell depletion in the spleen and lymph node observed with the divalent construct was increased 9- and 34-fold, respectively, compared with the monovalent construct. The additional sFv domain appears partially to compensate for steric hindrance of immunotoxin binding due to the large N-terminal toxin domain.

Animals↗
PubMed2001

Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients.

OBJECTIVE: To investigate whole body in vivo cysteine kinetics and its relationship to whole blood glutathione (GSH) synthesis rates in septic, critically ill pediatric patients and controls. DESIGN: Prospective cohort study. SETTING: Multidisciplinary intensive care unit and pediatric inpatient units at a children's hospital. PATIENTS: Ten septic pediatric patients and ten controls (children admitted to the hospital for elective surgery). INTERVENTIONS: Septic patients (age, 31 months to 17 yrs) and controls (age, 24 months to 21 yrs) received a 6-hr primed, constant, intravenous tracer infusion of l-[1-13C]cysteine. Blood samples were obtained to determine isotopic enrichment of plasma cysteine and whole blood [1-13C]cysteinyl-glutathione by gas-chromatography mass spectrometric techniques. The plasma flux and oxidation rate of cysteine and the fractional and absolute synthesis rates of GSH were determined. Septic patients received variable protein and energy intake, as per routine clinical management, and controls were studied in the early postabsorptive state. MEASUREMENTS AND MAIN RESULTS: Plasma cysteine fluxes were increased in the septic patients when compared with the controls (68.2 +/- 17.5 [sd] vs. 48.7 +/- 8.8 micromol x kg(-1) x hr(-1); p <.01), and the fraction of plasma cysteine flux associated with oxidative disposal was similar among the groups. The absolute rates of GSH synthesis in whole blood were decreased (p <.01) in the septic patients (368 +/- 156 vs. 909 +/- 272 micromol x L(-1) x day(-1)). The concentration of whole blood GSH also was decreased in the septic group (665.4 +/- 194 vs. 1059 +/- 334 microM; p <.01) CONCLUSIONS: Whole blood glutathione synthesis rates are decreased, by about 60%, in critically ill septic children receiving limited nutritional support. Plasma cysteine fluxes and concentration of cysteine were increased in the septic patients, suggesting a hypermetabolic state with increased protein breakdown. The mechanisms whereby GSH synthesis rates are decreased in these patients are probably multifactorial, presumably involving an inflammatory response in the presence of limited nutritional support. The role of nutritional modulation and the use of cysteine prodrugs in maintaining GSH concentration and synthesis remain to be established.

Adolescent↗
PubMed2001

Vagal nerve stimulation does not unkindle seizures.

The purpose of this study was to investigate a mechanism of action for the effect of vagal nerve stimulation on reducing seizures in patients with complex partial epilepsy. The hypothesis tested was that vagal nerve stimulation has an antikindling effect on epilepsy. The databases of two large clinical trials (E03, E05) were accessed, and statistical methods were applied using logarithmic transforms and regression analysis. Two parameters--duration of a patient's epilepsy before entering the clinical trial and the patient's seizure density before entering the clinical trial--were used as markers of subsequent seizure control during vagal nerve stimulation. In general, there was not a good fit to the regression lines, and the slope of the lines did not conform to the hypothesis. The hypothesis that vagal nerve stimulation may unkindle epileptic seizures was not supported.

Epilepsy, Complex Partial↗
PubMed2001

The predictive value of serum interleukins in recurrent respiratory papillomatosis: a preliminary study.

OBJECTIVE: IL-2 is the primary interleukin responsible for activation of the cell-mediated (Th1) arm of the immune response. Our objective was to determine whether a correlation existed between circulating levels of interleukin-2 as well as its soluble receptor (sIL-2R) and the clinical course of recurrent respiratory papillomatosis. METHODS AND MATERIALS: Fifteen children with a histological diagnosis of RRP were recruited. Age at the time of study, time since first diagnosis, and number of surgical interventions were recorded. The number of surgically treated recurrences per year was then calculated. We obtained serum samples from each of these 15 children and from 10 normal control subjects. We then performed in vitro determination of serum IL-2 and soluble IL-2 receptor levels using enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: IL-2 was significantly lower (136.6 vs. 199.9 pg/mL, P =.035) in papilloma patients than in control subjects. IL-2R was also lower in papilloma patients (531.7 vs. 785.8 U/mL, P =.025). There was no statistical age difference between the papilloma and control groups. Among patients with papillomatosis, IL-2 and sIL-2R levels were significantly higher in those with aggressive disease (>4 surgically treated recurrences per year) versus non-aggressive disease (179.2 vs. 99.2 pg/mL, P =.024; and 697 vs. 387 U/mL, P =.022). Age was also significantly lower in the aggressive papilloma group (P =.002). CONCLUSIONS: Levels of interleukin-2 and IL-2 receptor were significantly lower in patients with recurrent respiratory papillomatosis compared with normal children. These data support the presence of an aberrant cell-mediated immune response in children with recurrent respiratory papillomatosis.

Adolescent↗
PubMed2001

Improving physicians' HIV risk-assessment skills using announced and unannounced standardized patients.

OBJECTIVE: To evaluate feasibility and to validate a rating scale for two educational programs that use standardized patient-instructors (SPIs) in the office setting to improve physicians' HIV risk communication skills. DESIGN: Pilot randomized trial of announced and unannounced SPIs. PARTICIPANTS/SETTINGS: Twenty four primary care physicians in the Rochester, NY, area. MEASUREMENTS: The Rochester HIV Interview Rating Scale (RHIRS), HIV test ordering, physician satisfaction questionnaire. RESULTS: Physicians found the intervention useful, and predicted a positive effect on their future HIV-related communication. HIV test ordering and RHIRS scores increased similarly in both intervention groups. Announced SPI visits were more convenient and preferred by physicians. Cost for each SPI visit was $75. CONCLUSIONS: A brief office-based intervention using SPIs was feasible, well-accepted, convenient, and inexpensive. Announced SPIs were preferred to unannounced SPIs. Pilot results suggesting improvement in HIV-related communication should be confirmed in a larger randomized trial.

Adult↗
PubMed2001

Identification of proteins from Plasmodium falciparum that are homologous to reticulocyte binding proteins in Plasmodium vivax.

Plasmodium falciparum infections can be fatal, while P. vivax infections usually are not. A possible factor involved in the greater virulence of P. falciparum is that this parasite grows in red blood cells (RBCs) of all maturities whereas P. vivax is restricted to growth in reticulocytes, which represent only approximately 1% of total RBCs in the periphery. Two proteins, expressed at the apical end of the invasive merozoite stage from P. vivax, have been implicated in the targeting of reticulocytes for invasion by this parasite. A search of the P. falciparum genome databases has identified genes that are homologous to the P. vivax rbp-1 and -2 genes. Two of these genes are virtually identical over a large region of the 5' end but are highly divergent at the 3' end. They encode high-molecular-mass proteins of >300 kDa that are expressed in late schizonts and localized to the apical end of the merozoite. To test a potential role in merozoite invasion of RBCs, we analyzed the ability of these proteins to bind to mature RBCs and reticulocytes. No binding to mature RBCs or cell preparations enriched for reticulocytes was detected. We identified a parasite clone that lacks the gene for one of these proteins, showing that the gene is not required for normal in vitro growth. Antibodies to these proteins can inhibit merozoite invasion of RBCs.

Amino Acid Sequence↗