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Biomedical subjects

A de Jong

Publications and source records attributed to A de Jong.

At least 19 recordsLinked to original sources
PubMed2006

Plant sterol or stanol consumption does not affect erythrocyte osmotic fragility in patients on statin treatment.

OBJECTIVE: To assess the effects of plant sterol or stanol ester consumption on their incorporation into erythrocytes and their effects on osmotic fragility of red blood cells. DESIGN: Double-blind, randomized, placebo-controlled intervention trial. SUBJECTS AND INTERVENTION: Forty-one subjects on stable statin treatment - who already have increased serum plant sterol and stanol concentrations - first received for 4 weeks a control margarine. For the next 16 weeks, subjects were randomly assigned to one of three possible interventions. Eleven subjects continued with control margarine, 15 subjects with plant sterol ester enriched and 15 subjects with plant stanol ester-enriched margarine. Daily plant sterol or stanol intake was 2.5 g. Erythrocyte haemolysis was measured spectrophotometrically at five different saline concentrations. RESULTS: Despite significant (P = 0.004) increases of, respectively, 42 and 59% in cholesterol-standardized serum sitosterol and campesterol concentrations in the plant sterol group as compared to the control group, campesterol levels in the red blood cells did not change (P = 0.196). Osmotic fragility did not change significantly (P = 0.757) in the plant sterol and plant stanol groups as compared to the control group. CONCLUSION: We conclude that plant sterol and stanol ester consumption for 16 weeks does not change osmotic fragility of erythrocytes in statin-treated patients. SPONSORSHIP: Netherlands Organisation for Health Research and Development (Program Nutrition: Health, Safety and Sustainability, Grant 014-12-010).

Anticholesteremic Agents↗
PubMed2006

Mapping the pathways to staphylococcal pathogenesis by comparative secretomics.

The gram-positive bacterium Staphylococcus aureus is a frequent component of the human microbial flora that can turn into a dangerous pathogen. As such, this organism is capable of infecting almost every tissue and organ system in the human body. It does so by actively exporting a variety of virulence factors to the cell surface and extracellular milieu. Upon reaching their respective destinations, these virulence factors have pivotal roles in the colonization and subversion of the human host. It is therefore of major importance to obtain a clear understanding of the protein transport pathways that are active in S. aureus. The present review aims to provide a state-of-the-art roadmap of staphylococcal secretomes, which include both protein transport pathways and the extracytoplasmic proteins of these organisms. Specifically, an overview is presented of the exported virulence factors, pathways for protein transport, signals for cellular protein retention or secretion, and the exoproteomes of different S. aureus isolates. The focus is on S. aureus, but comparisons with Staphylococcus epidermidis and other gram-positive bacteria, such as Bacillus subtilis, are included where appropriate. Importantly, the results of genomic and proteomic studies on S. aureus secretomes are integrated through a comparative "secretomics" approach, resulting in the first definition of the core and variant secretomes of this bacterium. While the core secretome seems to be largely employed for general housekeeping functions which are necessary to thrive in particular niches provided by the human host, the variant secretome seems to contain the "gadgets" that S. aureus needs to conquer these well-protected niches.

Bacterial Proteins↗
PubMed2003

Interplay between human papillomaviruses and dendritic cells.

The design of the human papillomavirus (HPV) infection cycle is tightly fitted to the differentiation program of its natural host, the keratinocyte. This has important consequences for the role of antigen-presenting cells in the priming of antiviral immunity. The confinement of HPV infection to epithelia puts the epithelial dendritic cell, the Langerhans cell (LC), in charge of the induction of T cell-dependent immunity. Because HPV-infected keratinocytes cannot reach the regional lymphoid organs, and HPV-infection of LCs does not result in viral gene expression, priming of antiviral T cells exclusively depends on cross-presentation of viral antigens by the LC. Sensitization of the immune system in the regional lymphoid organs elicits systemic anti-HPV immunity as well as intraepithelial immune surveillance by memory-type intraepithelial T cells and locally produced antibodies. The high rate of spontaneous rejections of high-risk HPV-infections and HPV-positive premalignant lesions indicates that in general the LC-driven antigen presentation machinery is capable of raising an effective immune defense against HPV. Epidemiological studies also reveal that a decrease in the vigilance of the immune system is readily exploited by HPV to escape immune destruction, resulting in persistent infections and development of HPV-positive cancers. In view of the inherent antigenicity of HPV, immune intervention strategies constitute a promising approach for both the prevention and the therapeutic treatment of HPV-induced diseases. Importantly, the mechanisms that govern the induction and effector phases of the intraepithelial immune surveillance against HPV must be taken into account when designing such strategies.

Antigen-Presenting Cells↗
PubMed2002

Enhancement of human papillomavirus (HPV) type 16 E6 and E7-specific T-cell immunity in healthy volunteers through vaccination with TA-CIN, an HPV16 L2E7E6 fusion protein vaccine.

TA-CIN is a vaccine that comprises the human papillomavirus (HPV) type 16 L2, E6 and E7 as a single fusion protein. In a mouse model, TA-CIN effectively prevented outgrowth of HPV16-positive tumour cells. To assess the safety and immunogenicity of TA-CIN, a dose escalating (26, 128, 533 micro g), double blind and placebo-controlled phase I study was conducted in 40 healthy volunteers. TA-CIN was administered without adjuvant by intramuscular injection on weeks 0, 4 and 8. No serious adverse events of the vaccination were reported during the study. Both IgG antibodies and proliferative responses against TA-CIN were elicited at all three doses. More importantly, T-cell immunity against the HPV16 E6 and E7 oncoproteins was detected by IFN gamma ELISPOT in 8/11 evaluable subjects vaccinated with the 533 micro g dose.

Adult↗
PubMed2002

[Screening for carriers of the fragile X syndrome; ethical exploration].

Large-scale population screening for carriers of fragile X syndrome is premature. Notably the limited possibilities to detect carriers (of an instable premutation) in the general population with certainty, poses some ethical dilemmas. The possible psychological consequences of this are unknown. A pilot study can only be started if the added value of population screening as opposed to cascade screening is plausible, and the requirement of proportionality is satisfied. If this is the case, preconceptional screening is preferable to prenatal screening. Information should be provided in a process-like manner as this fits in best with the decision-making process that possibly follows participation in a population screening for carriers of fragile X syndrome. Further research into the ethics of cascade screening is desirable. This screening can be carried out on a complementary basis to population screening.

Ethics, Professional↗
PubMed2001

The role of postoperative chest radiography in pediatric tracheotomy.

A postoperative chest radiograph has traditionally been obtained after tracheotomies to evaluate for the presence of a pneumothorax and to assess tube position. Several recent studies in adults have questioned the usefulness of routine postoperative chest radiography in uncomplicated cases, but the role of post-operative chest radiography in pediatric patients has not been previously reviewed. We performed this study to examine the clinical utility of post-tracheotomy chest radiography in pediatric patients and determine if this routine practice impacts patient management enough to merit continued usage. A retrospective review was performed of 200 consecutive pediatric patients who underwent tracheotomies by the otolaryngology service in a tertiary care pediatric hospital from January 1994 to June 1999. All patients received postoperative chest radiographs. Five of 200 patients had a new postoperative radiographic finding, with three requiring interventions. Two patients required chest tube placement for pneumothorax, and one patient required tracheostomy tube change for repositioning. Fifty-one patients, including both pneumothoraces, exhibited clinical signs of pneumothorax (decreased breath sounds or oxygen saturation) in the immediate postoperative period. Chest X-ray ruled out a pneumothorax in the remaining 49 patients. The majority of these 51 patients were less than 2 years old (94%, P=0.002) or weighed less than 17 kg (89%, P=0.004). Postoperative chest X-rays yielded clinically relevant information in 168 patients that fell into one or more of four high risk categories: age less than 2, weight less than 17 kg, emergent procedures, or concomitant central line placement. Avoiding chest X-rays in the remaining 32 patients would have resulted in potential savings of $5000, which does not reflect the actuarial cost of a missed complication. Since the majority of our patients (84%) fell into a high-risk category, we feel it would be prudent to continue obtaining postoperative chest radiographs following all pediatric tracheotomies.

Chest Tubes↗
PubMed2001

Natural T-helper immunity against human papillomavirus type 16 (HPV16) E7-derived peptide epitopes in patients with HPV16-positive cervical lesions: identification of 3 human leukocyte antigen class II-restricted epitopes.

Tumor-specific T-helper (Th) immunity was found to play a pivotal role in the natural and vaccine-induced immune defense against tumors. Since the majority of cervical cancers express human papillomavirus type 16 (HPV16) E7 oncoprotein, it is important to investigate the Th response against this target antigen in detail. By means of PBMC cultures from HLA-typed healthy donors, we identified the central part of HPV16 E7 (E7(41-72)) as the major immunogenic region within this antigen. Furthermore, we mapped 3 distinct Th epitopes within this region (DR15/E7(50-62), DR3/E7(43-77), DQ2/E7(35-50)). In a parallel approach, employing IFN-gamma ELISPOT analysis, we detected Th immunity against HPV16 E7 in subjects with HPV16+ lesions. Several of these responses matched with the 3 Th epitopes defined in our study. A number of other HPV16+ subjects did not display any E7-specific type 1 cytokine-producing T-cell immunity, indicating failure of the immune response. Our combined data argue for more extensive as well as longitudinal analysis of HPV16-specific T-cell immunity using the ELISPOT assay described, as well as for HPV-specific vaccination of individuals with HPV+ lesions.

Cancer Vaccines↗
PubMed2001

Role of variability in microvascular resistance on fractional flow reserve and coronary blood flow velocity reserve in intermediate coronary lesions.

BACKGROUND: Fractional flow reserve (FFR) and coronary blood flow velocity reserve (CFR) represent physiological quantities used to evaluate coronary lesion severity and to make clinical decisions. A comparison between the outcomes of both diagnostic techniques has not been performed in a large cohort of patients with intermediate coronary lesions. METHODS AND RESULTS: FFR and CFR were assessed in 126 consecutive patients with 150 intermediate coronary lesions (between 40% and 70% diameter stenosis by visual assessment). Agreement between outcomes of FFR and CFR, categorized at cut-off values of 0.75 and 2.0, respectively, was observed in 109 coronary lesions (73%), whereas discordant outcomes were present in 41 lesions (27%). In 26 of these 41 lesions, FFR was <0.75 and CFR>or=2.0 (group A); in the remaining 15 lesions, FFR was >or=0.75 and CFR<2.0 (group B). Minimum microvascular resistance, defined as the ratio of mean distal pressure to average peak blood flow velocity during maximum hyperemia, showed a large variability (overall range, 0.65 to 4.64 mm Hg x cm(-1) x s(-1)) and was significantly higher in group B than in group A (2.42+/-0.77 versus 1.91+/-0.70 mm Hg x cm(-1) x s(-1); P:=0.034). CONCLUSIONS: Our findings demonstrate the prominent role of microvascular resistance in modulating the relationship between FFR and CFR and emphasize the importance of combined pressure and flow velocity measurements to evaluate coronary lesion severity and microvascular involvement.

Angina Pectoris↗
PubMed2001

Implications of the simultaneous presence of metronidazole-susceptible and -resistant Helicobacter pylori colonies within a single biopsy specimen.

This study examined whether the simultaneous presence of metronidazole-susceptible and -resistant Helicobacter pylori colonies in a single biopsy specimen is caused by a multiple strain infection with a susceptible and a resistant strain or by two subpopulations within a single strain. Single colonies obtained from seven biopsy specimens known to harbour both susceptible and resistant Helicobacter pylori were fingerprinted by restricted fragment length polymorphism typing of the ureC gene and by the random amplified polymorphic DNA procedure. Metronidazole susceptibility was determined by the E test. The results indicated that the occurrence of metronidazole-resistant and metronidazole-susceptible bacteria within a single biopsy does not imply the presence of a multiple strain infection with one resistant and one sensitive strain.

Anti-Bacterial Agents↗
PubMed2001

Fractional flow reserve, absolute and relative coronary blood flow velocity reserve in relation to the results of technetium-99m sestamibi single-photon emission computed tomography in patients with two-vessel coronary artery disease.

OBJECTIVES: We sought to perform a direct comparison between perfusion scintigraphic results and intracoronary-derived hemodynamic variables (fractional flow reserve [FFR]; absolute and relative coronary flow velocity reserve [CFVR and rCFVR, respectively]) in patients with two-vessel disease. BACKGROUND: There is limited information on the diagnostic accuracy of intracoronary-derived variables (CFVR, FFR and rCFVR) in patients with multivessel disease. METHODS: Dipyridamole technetium-99m sestamibi (MIBI) single-photon emission computed tomography (SPECT) was performed in 127 patients. The presence of reversible perfusion defects in the region of interest was determined. Within one week, angiography was performed; CFVR, rCFVR and FFR were determined in 161 coronary lesions after intracoronary administration of adenosine. The predictive value for the presence of reversible perfusion defects on MIBI SPECT of CFVR, rCFVR and FFR was evaluated by the area under the curve (AUC) of the receiver operating characteristics curves. RESULTS: The mean percentage diameter stenosis was 57% (range 35% to 85%), as measured by quantitative coronary angiography. Using per-patient analysis, the AUCs for CFVR (0.70 +/- 0.052), rCFVR (0.72 +/- 0.051) and FFR (0.76 +/- 0.050) were not significantly different (p = NS). The percentages of agreement with the results of MIBI SPECT were 76%, 78% and 77% for CFVR, rCFVR and FFR, respectively. Per-lesion analysis, using all 161 measured lesions, yielded similar results. CONCLUSIONS: The diagnostic accuracy of three intracoronary-derived hemodynamic variables, as compared with the results of perfusion scintigraphy, is similar in patients with two-vessel coronary artery disease. Cut-offvalues of 2.0 for CFVR, 0.65 for rCFVR and 0.75 for FFR can be used for clinical decision-making in this patient cohort. Discordant results were obtained in 23% of the cases that require prospective evaluation for appropriate patient management.

Adult↗
PubMed2001

The accuracy of the Helicobacter pylori stool antigen test in diagnosing H. pylori in treated and untreated patients.

OBJECTIVE AND DESIGN: To evaluate the performance of the Helicobacter pylori stool antigen test (HpSA test) in detecting H. pylori infection and monitoring the effect of treatment. This was done in two separate studies using either a biopsy or the 13C-urea breath test based 'gold standard' (in untreated and treated patients, respectively). SETTING: Endoscopy units of two general hospitals. PATIENTS: One hundred and twenty-eight dyspeptic patients undergoing endoscopy in the first study. Sixty-five patients receiving anti-H. pylori treatment in the second study. RESULTS: Sensitivity and specificity in untreated patients were 96.3% and 81.8%, respectively. Seven days after treatment, these figures were 20% and 95%, and 4 weeks after treatment they were 40% and 95%. CONCLUSION: The HpSA test is accurate in untreated patients but fails in monitoring treatment success.

Adolescent↗
PubMed2000

Transport of amino acids (L-valine, L-lysine, L-glutamic acid) and sucrose into plasma membrane vesicles isolated from cotyledons of developing pea seeds.

Transport of the amino acids L-valine, L-lysine, and L-glutamic acid and of sucrose was studied in plasma membrane vesicles isolated from developing cotyledons of pea (Pisum sativum L. cv. Marzia). The vesicles were obtained by aqueous polymer two-phase partitioning of a microsomal fraction and the uptake was determined after the imposition of a H(+)-gradient (DeltapH, inside alkaline) and/or an electrical gradient (Deltapsi, inside negative) across the vesicle membrane. In the absence of gradients, a distinct, time-dependent uptake of L-valine was measured, which could be enhanced about 2-fold by the imposition of DeltapH. The imposition of Deltapsi stimulated the influx of valine by 20%, both in the absence and in the presence of DeltapH. Uptake of L-lysine was more strongly stimulated by Deltapsi than by DeltapH, and its DeltapH-dependent uptake was enhanced about 6-fold by the simultaneous imposition of Deltapsi. In the absence of gradients the uptake of L-glutamic acid was about 2-fold higher than that of L-valine, but it was not detectably affected by DeltapH or Deltapsi. Although the transport of sucrose was very low, a stimulating effect of DeltapH could be clearly demonstrated. The results lend further support to the contention that during seed development cotyledonary cells employ H(+)-symporters for the active uptake of sucrose and amino acids.

Amino Acids↗
PubMed2000

A plasma membrane-enriched fraction isolated from the coats of developing pea seeds contains H(+)-symporters for amino acids and sucrose.

Aqueous polymer two-phase partitioning was used to obtain a plasma membrane-enriched fraction from coats of developing pea (Pisum sativum L.) seeds in the filling stage. Uptake of amino acids and sucrose by vesicles from this fraction was determined after imposition of gradients of proton concentration (DeltapH, inside alkaline) and electrical potential (Deltapsi, inside negative) across the vesicle membrane. The uptake of sucrose and the amino acids L-valine, L-lysine, and L-glutamic acid was stimulated by the imposition of DeltapH. The imposition of Deltapsi, either in the presence or in the absence of DeltapH, stimulated the uptake of L-valine and L-lysine, but had no detectable effect on the uptake of sucrose and L-glutamic acid. The proton-motive-force-driven uptake of all four substrates was abolished by the protonophore carbonylcyanide m-chlorophenyl-hydrazone (CCCP). The results demonstrate the presence of H(+)-symporters for sucrose and amino acids in pea seed coats. This is running counter to the previously reported finding that their uptake by isolated pea seed coats was insensitive to CCCP, and that the uptake of sucrose, L-valine, and L-glutamic acid displayed linear kinetics. Possible causes of this discrepancy will be discussed.

Amino Acids↗
PubMed2000

Human immunodeficiency virus-positive individuals with oral hairy leukoplakia are able to mount cytotoxic T lymphocyte responses to Epstein-Barr virus.

OBJECTIVE: Oral hairy leukoplakia (OHL) is a white lesion of the tongue that is caused by Epstein-Barr virus (EBV) and occurs mainly in people infected with human immunodeficiency virus (HIV). The aim of this study was to determine whether the presence of OHL reflects the absence of EBV-specific cytotoxic T lymphocyte (CTL) activity. SUBJECTS AND METHODS: EBV-specific CTL responses were measured in HIV-positive homosexual men with OHL, HIV-positive homosexual men without OHL, and HIV-negative homosexual men. Also, the phenotypes of cells responsible for EBV-specific responses were studied. RESULTS: Eighty percent (8/10) of HIV-positive subjects with OHL, 52% (12/23) of HIV-positive subjects without OHL, and 83% (15/18) HIV-negative subjects had a positive anti-EBV CTL response (P = 0.004, Kruskal-Wallis test). Two HIV-positive subjects showed a greater anti-EBV CTL response after developing OHL than before the appearance of OHL Additional experiments showed that CD8-positive T cells and CD4-positive T cells were responsible for the EBV-specific CTL responses. CONCLUSION: Our data show more EBV-specific CTL activities in HIV-positive individuals with OHL than in HIV-positive individuals without OHL. Whether the presence of EBV-specific CTL contributes to resolution of OHL remains to be clarified.

Adult↗
PubMed2000

[Determination of breakpoints for veterinary medically relevant antibiotics for resistance assessment of veterinary pathogens].

This article describes the meaning of the term clinical breakpoint. This is followed by a discussion of the parameters that need to be considered when setting valid breakpoints for active substances in veterinary medicine; in doing so we closely follow equivalent regulations and guidelines on the establishment of breakpoints in human medicine. Along with pharmacokinetic data and the results of clinical efficacy tests, susceptibility data of relevant organisms play a key role in the establishment of breakpoints. Published breakpoints are currently only available for a few modern drugs in veterinary medicine.

Animals↗
PubMed2000

Development of the International Classification of Mental Health Care (ICMHC).

OBJECTIVE: Evaluations of the process of providing mental health care have been hampered because a tool to systematically describe the interventions actually provided by the services was lacking. In this paper the development of such a tool (the International Classification of Mental Health Care; ICMHC) is described. METHOD: Subsequent versions of the ICMHC were developed, using comments from experts in 24 WHO field centres and results from a number of field trials. In the final version 10 Modalities of Care can be used to describe Modules of Care, using the Level of Specialization scale. The inter-rater reliability of this version was evaluated by the Italian research team, using data from 43 services. RESULTS: Reliability ranged from excellent for nine modalities to reasonably good for the remaining modality. CONCLUSION: In the context of evaluation studies, the ICMHC can be used to describe systematically mental health care interventions.

Cultural Characteristics↗