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Biomedical subjects

J Barrett

Publications and source records attributed to J Barrett.

At least 73 records · Page 4Linked to original sources
PubMed2000

Treatment of dysthymia and minor depression in primary care: A randomized controlled trial in older adults.

CONTEXT: Insufficient evidence exists for recommendation of specific effective treatments for older primary care patients with minor depression or dysthymia. OBJECTIVE: To compare the effectiveness of pharmacotherapy and psychotherapy in primary care settings among older persons with minor depression or dysthymia. DESIGN: Randomized, placebo-controlled trial (November 1995-August 1998). SETTING: Four geographically and clinically diverse primary care practices. PARTICIPANTS: A total of 415 primary care patients (mean age, 71 years) with minor depression (n = 204) or dysthymia (n = 211) and a Hamilton Depression Rating Scale (HDRS) score of at least 10 were randomized; 311 (74.9%) completed all study visits. INTERVENTIONS: Patients were randomly assigned to receive paroxetine (n = 137) or placebo (n = 140), starting at 10 mg/d and titrated to a maximum of 40 mg/d, or problem-solving treatment-primary care (PST-PC; n = 138). For the paroxetine and placebo groups, the 6 visits over 11 weeks included general support and symptom and adverse effects monitoring; for the PST-PC group, visits were for psychotherapy. MAIN OUTCOME MEASURES: Depressive symptoms, by the 20-item Hopkins Symptom Checklist Depression Scale (HSCL-D-20) and the HDRS; and functional status, by the Medical Outcomes Study Short-Form 36 (SF-36) physical and mental components. RESULTS: Paroxetine patients showed greater (difference in mean [SE] 11-week change in HSCL-D-20 scores, 0.21 [0. 07]; P =.004) symptom resolution than placebo patients. Patients treated with PST-PC did not show more improvement than placebo (difference in mean [SE] change in HSCL-D-20 scores, 0.11 [0.13]; P =.13), but their symptoms improved more rapidly than those of placebo patients during the latter treatment weeks (P =.01). For dysthymia, paroxetine improved mental health functioning vs placebo among patients whose baseline functioning was high (difference in mean [SE] change in SF-36 mental component scores, 5.8 [2.02]; P =. 01) or intermediate (difference in mean [SE] change in SF-36 mental component scores, 4.4 [1.74]; P =.03). Mental health functioning in dysthymia patients was not significantly improved by PST-PC compared with placebo (P>/=.12 for low-, intermediate-, and high-functioning groups). For minor depression, both paroxetine and PST-PC improved mental health functioning in patients in the lowest tertile of baseline functioning (difference vs placebo in mean [SE] change in SF-36 mental component scores, 4.7 [2.03] for those taking paroxetine; 4.7 [1.96] for the PST-PC treatment; P =.02 vs placebo). CONCLUSIONS: Paroxetine showed moderate benefit for depressive symptoms and mental health function in elderly patients with dysthymia and more severely impaired elderly patients with minor depression. The benefits of PST-PC were smaller, had slower onset, and were more subject to site differences than those of paroxetine.

Aged↗
PubMed2000

Pharmacologic doses of granulocyte colony-stimulating factor affect cytokine production by lymphocytes in vitro and in vivo.

Peripheral blood stem cell (PBSC) transplantation is successful in improving engraftment without increasing acute graft-versus-host disease (GVHD), despite much larger numbers of T cells in unmanipulated PBSCs than in bone marrow grafts. In mouse models and retrospective human studies, granulocyte colony-stimulating factor (G-CSF) therapy has been associated with less acute GVHD. We studied the effect of G-CSF on interferon (IFN)-gamma and IL-4 expression in CD4(+) lymphocytes. CD4(+) cells co-cultivated with G-CSF and stimulated with PHA or CD3 monoclonal antibodies showed significant decreases in IFN-gamma and increases in IL-4 expression (n = 13; P <. 01). G-CSF appeared to have a direct effect on CD4(+) cells independent of monocytes present in the culture because purified CD4(+) cells exposed to G-CSF, washed, and cocultivated with untreated monocytes demonstrated similar changes in IFN-gamma and IL-4 expression, whereas untreated CD4(+) cells cocultured with G-CSF-stimulated monocytes behaved as controls. We then studied peripheral blood mononuclear cells (PBMCs) from G-CSF-mobilized PBSC donors. When their PBMCs were cultured with PHA or CD3 monoclonal antibody, the percent of IFN-gamma-expressing cells decreased by a mean of 55% and 42%, respectively, whereas the percent of IL-4-containing cells increased by a mean of 39% and 58%, respectively, following G-CSF stimulation. Increased apoptosis of IFN-gamma-producing CD4(+) cells was not responsible for the shift in TH1/TH2 subsets. G-CSF-R mRNA was present in both CD4(+) and CD8(+) cells. These results suggest that G-CSF decreases IFN-gamma and increases IL-4 production in vitro and in vivo and likely modulates a balance between TH1 and TH2 cells, an effect that may be important in PBSC transplantation.

Antibodies, Monoclonal↗
PubMed2000

Characterization of an overexpressed spindle protein during a baculovirus infection.

The nucleopolyhedrovirus CfDEFNPV contains a gene encoding a viral protein, which accumulates as bipyramidal inclusion bodies (spindles) in the cytoplasm of infected cells. The spindles appear as early as 24 h postinfection, approximately 1 day earlier than viral occlusion bodies (OBs). Purification and characterization of the spindle protein was complicated by the fact that the OBs copurified with the spindles. We therefore modified CfDEFNPV by replacing the polyhedrin gene (plh) with a cassette containing the green fluorescent protein (GFP) gene. The recombinant virus did not produce OBs; however, the synthesis and morphogenesis of the spindles were not altered. When analyzed by SDS-PAGE, the spindles produced a 50-kDa protein, which was termed spindlin. Tunicamycin inhibition and endoglycosidase studies showed that spindlin was glycosylated. The N-terminus of spindlin was sequenced and its gene (gp50) was located on the viral genome. The gene was cloned and sequenced. Homologs of gp50 were found in several baculoviruses as well as in entomopoxviruses (EPV). In the latter virus, the homologous gene is that of fusolin, which also encodes a protein that forms spindle-shaped inclusion bodies in the cytoplasm of infected cells. Immunoblot analysis indicated that spindlin and fusolin were not serologically related, even though they share conserved polypeptide domains. Sequence analysis showed that gp50 of CfDEFNPV contains two late promoter motifs (TTAAG) in its 5' flanking region. Both were used, but the proximal motif (-14 to -18 nt relative to the ATG) was the primary sequence from which most of the mRNA was initiated. When gp50 was cloned in a heterologous baculovirus expression system, spindlin was synthesized, although the spindles were irregular in shape. This suggested that the spindle structure may be species-specific or it may require more than one gene product for its morphogenesis.

Amino Acid Sequence↗
PubMed2000

Relationship between expression of the KAI1 metastasis suppressor and other markers of advanced bladder cancer.

Expression of a newly described inhibitor of tumour metastasis, KAI1, was examined in bladder cancer progression and compared with the expression of p53 and pRb, which are markers of advanced disease. KAI1 mRNA (by in situ hybridization) and protein levels (by immunohistochemistry) were examined in 135 paraffin-embedded bladder tissue sections. Significant decreases in KAI1 mRNA and protein levels were detected between normal and tumour tissue (p<0.001 and p=0.026, respectively), and between non-invasive and invasive tumours (p=0.046 and p<0.001, respectively). Loss of KAI1 protein expression was accompanied by a shift in staining pattern from a uniform distribution to a weaker, membranous or heterogeneous pattern. Normal tissue and low-grade tumours showed little p53 protein staining. High level staining (indicative of mutant p53) was associated with increased grade in non-invasive tumours (p=0.031) but was not significantly higher in invasive tumours. Whilst p53 protein staining increased with malignant progression and KAI1 mRNA expression decreased, there was no significant correlation between the two patterns (p=0.33, adjusted for group, p=0.18) or when only cancer samples were analysed (p=0.065, adjusted for group, p=0.26), even when taking into account overexpression of MDM-2 protein as a pathway for inactivation of p53. There was no correlation between loss of KAI1 mRNA expression and gain of abnormal pRb staining (p=0. 30, or adjusted for tumour samples only, p=0.59). These results suggest that loss of KAI1 expression is associated with invasive bladder cancer, but is not related to mutation of p53 or to loss of normal pRb expression.

Antigens, CD↗
PubMed2000

Inhibition of glutathione S-transferases (GSTs) from parasitic nematodes by extracts from traditional Nigerian medicinal plants.

Piliostigma thonningii, Ocimum gratissimum, Nauclea latifolia and Alstonia boonei are used in Nigerian traditional medicines against gastrointestinal helminths of animals and man. Proanthocyanidins were detected in Piliostigma and Nauclea, but not Alstonia or Ocimum. Extracts of these plants killed 50% of brine shrimp nauplii at <10 ppm (Nauclea), 100 ppm (Piliostigma) and <1000 ppm (Ocimum and Alstonia), the Nauclea LD50 being similar to the anthelmintic drug piperazine. Extracts were also toxic to the parasitic nematode Haemonchus infective L3 stage. Nematode glutathione-S-transferases (GSTs) are potential drug targets. Apart from Alstonia all the medicinal plants contained heat-stable inhibitory activities against recombinant Ascaris and Onchocerca GSTs in vitro. Piliostigma, Ocimum and Nauclea had IC50s of 2, 10 and 15 microg/mL respectively for Ascaris GST and 4, 8, 28 microg/mL respectively for Onchocerca GST. We suggest that the inhibitory properties of some of these Nigerian plant extracts against GST may contribute to the pharmacological basis of their efficacy against helminths in traditional herbal use.

Animals↗
PubMed2000

Investigation of Fasciola hepatica sample preparation for two-dimensional electrophoresis.

This paper investigates the preparation of Fasciola hepatica samples for two-dimensional electrophoresis (2-DE). Whole samples were prepared by both hot sodium dodecyl sulfate (SDS) solubilisation and precipitation using trichloroacetic acid (TCA) to remove nonprotein contaminants and to inactivate endogenous proteases. Sample preparation had a marked influence on the 2-DE gel profile. TCA precipitation resulted in no measurable improvement in the profile observed, compared to the untreated control. Solubilisation of sample with hot SDS increased the number of protein spots, as did TCA precipitation with the addition of phosphotungstic acid. The preparation of excretory-secretory (ES) products poses problems due to both high salt concentrations and low protein concentration. All precipitation methods used to overcome this gave similar profiles, except acetone alone, which caused depletion of the larger proteins. TCA in acetone gave the best result, similar to that obtained by centrifugal filtration of the sample. Overcrowding of spots in some regions of the 2-DE gel occurred in the whole Fasciola hepatica sample. This problem was alleviated by differential solubilisation, which also resulted in the enrichment of some proteins.

Animals↗
PubMed2000

Running focus groups with elderly and disabled elderly participants.

This paper is based on a study to determine the information needs of elderly, disabled elderly people, and of their carers, in the UK. Four focus groups were run with a total of 20 participants to identify major themes and aid in the creation of a questionnaire for a national survey. This paper does not describe the findings of the focus groups but reports on the lessons learned from running them, in the light of the increasing importance of such methods. A number of difficulties arose, most associated with age-related declines in sensory, perceptual, cognitive and communication abilities. These difficulties are described, together with the steps that need to be taken to eliminate, or at least ameliorate, them, so that this powerful method of collecting information can be used fruitfully on elderly and disabled elderly people.

Aged↗
PubMed2000

Experience with over 2500 diagnostic peritoneal lavages.

This study was undertaken to confirm the safety and efficacy of diagnostic peritoneal lavage (DPL) for trauma patients. A prospectively maintained database of all DPLs performed in the past 75 months was analyzed. A red blood cell count of 100,000/mm(3) was considered positive for injury in blunt trauma; 10,000/mm(3) was considered positive for peritoneal penetration in penetrating trauma. Information relative to type of injury, DPL result, laparotomy result and complications, was analysed to determine if DPL was more or less suited to any specific indication or type of patient. Over a 75 month period, 2501 DPLs were performed at our urban level I trauma center. The overall sensitivity, specificity and accuracy for the above thresholds were 95, 99 and 98%. The majority (2409, 96%) were performed using percutaneous or "closed" seldinger technique. Ninety-two (4%) were performed using open technique because of pelvic fractures, previous scars and pregnancy. Open DPL was less sensitive than closed DPL in patients who sustained blunt trauma (90 vs 95%) but slightly more sensitive in determining penetration (100 vs 96%). Overall, there were 21 complications (0.8%). There was no difference in complication rate between open and closed DPL. In conclusion, DPL remains a highly accurate, sensitive and specific test with an extremely low complication rate. It can be performed either open or closed with comparable results. We recommend its use in the evaluation of both blunt and penetrating trauma.

Abdominal Injuries↗
PubMed2000

Myelodysplastic syndrome and aplastic anemia: distinct entities or diseases linked by a common pathophysiology?

It is often difficult to distinguish myelodysplastic syndrome (MDS) from severe aplastic anemia (SAA) because both can present with profoundly hypocellular bone marrows. The distinction matters because although both conditions are complicated by pancytopenia, the risk of progression to acute leukemia is much greater in MDS. This chapter reexamines the relationship between SAA and MDS. The clinical and morphological features and pathophysiology of AA (including moderate and severe forms of acquired AA) are compared with MDS and hypoplastic MDS, with particular reference to new observations implicating autoimmune processes in both conditions. SAA and hypoplastic MDS (HMDS) are discussed in the light of these findings and attempts to separate nonevolving bone marrow failure syndromes from marrow failure progressing to acute leukemia are reviewed. The weight of evidence supports a common pathophysiology and, more speculatively, a common etiology for at least some forms of AA and MDS.

Anemia, Aplastic↗
PubMed2000

Parasite proteomics.

Proteomics offers a new set of tools for investigating parasites and parasite-associated disease. In this article, John Barrett, Jim Jefferies and Peter Brophy describe the key technologies involved, including two-dimensional gel electrophoresis, image analysis, biological mass spectroscopy and database searching. The potential applications of proteomics in drug and vaccine discovery are reviewed, as are possible future developments.

Electrophoresis, Gel, Two-Dimensional↗
PubMed2000

Correction of the influence of baseline artefacts and electrode polarisation on dielectric spectra.

The deconvolution of biological dielectric spectra can be difficult enough with artefact-free spectra but is more problematic when machine baseline artefacts and electrode polarisation are present as well. In addition, these two sources of anomalies can be responsible for significant interference with dielectric biomass measurements made using one- or two-spot frequencies. The aim of this paper is to develop mathematical models of baseline artefacts and electrode polarisation which can be used to remove these anomalies from dielectric spectra in a way that can be easily implemented on-line and in real-time on the Biomass Monitor (BM). We show that both artefacts can be successfully removed in solutions of organic and inorganic ions; in animal cell and microbial culture media; and in yeast suspensions of varying biomass. The high quality of the compensations achieved were independent of whether gold and platinum electrodes were used; the electrode geometry; electrode fouling; current density; the type of BM; and of whether electrolytic cleaning pulses had been applied. In addition, the calibration experiments required could be done off-line using a simple aqueous KCl dilution series with the calibration constants being automatically calculated by a computer without the need for user intervention. The calibration values remained valid for a minimum of 3 months for the baseline model and indefinitely for the electrode polarisation one. Importantly, application of baseline correction prior to polarisation correction allowed the latter's application to the whole conductance range of the BM. These techniques are therefore exceptionally convenient to use under practical conditions.

Artifacts↗
PubMed2000

Molluscicidal activity of some Saudi Arabian euphorbiales against the snail Biomphalaria pfeifferi.

The comparative susceptibility of the snail vector of intestinal schistosomiasis, Biomphalaria pfeifferi to the action of extracts from Saudi Arabian Euphorbiales has been determined. Methanol and chloroform extracts of the plants tested (Jatropha glauca, Euphorbia helioscopia and Euphorbia schimperiana) were the most promising from the molluscicidal point of view with LD(50) values in the range 10-100 ppm.

Animals↗
PubMed2000

Donor leukocyte infusions in acute lymphocytic leukemia.

Donor leukocyte infusion (DLI) has well-documented activity in CML but the role of DLI in other diseases is less well defined. To evaluate the strategy in acute lymphocytic leukemia (ALL) we evaluated 44 ALL patients from 27 centers who were treated with DLI. Patients with persistent or recurrent disease received DLI from the original marrow donor (30 matched related, four mismatched family, and 10 matched unrelated). Chemotherapy was given before DLI to 28 patients. Of 15 patients who received no pre-DLI chemotherapy, two achieved complete remissions, lasting 1112 and 764+ days. In four patients who received DLI as consolidation of remission induced by chemotherapy or immunosuppression-withdrawal, duration of remission post DLI was 65, 99, 195 and 672+ days. Of 25 patients who received DLI in the nadir after chemotherapy, 13 survived > or =30 days post DLI but did not achieve remission, seven died within less than 30 days post DLI, and five entered remissions that lasted 42, 68, 83, 90, 193 days. Seven patients who did not respond to the initial DLI received a second DLI; none of these patients attained durable remission. Eighteen of 37 evaluable patients developed acute GVHD and five of 20 evaluable patients developed chronic GVHD. Overall actuarial survival is 13% at 3 years. In conclusion, DLI has limited benefit in ALL. New approaches are needed in this group of patients.

Actuarial Analysis↗