TIMP-3 promoter gene polymorphisms in BFL.
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Bird Fancier's Lung↗
Biomedical subjects
R Janssen
Publications and source records attributed to R Janssen.
Linkage of myostatin pathway genes with knee strength in humans.
This study was the first to explore the potential role of the myostatin (GDF8) pathway in relation to muscle strength and estimated muscle cross-sectional area in humans using linkage analysis with a candidate gene approach. In young male sibs (n = 329) 11 polymorphic markers in or near 10 candidate genes from the myostatin pathway were genotyped. Muscle mass was estimated by anthropometric measurements, and maximal knee strength was evaluated using isokinetic dynamometers (Cybex NORM). Single-point nonparametric variance components and linear quantitative trait locus regression linkage analysis methods were used. Linkage patterns were observed between knee extension and flexion peak torque with markers D2S118 (GDF8), D6S1051 (CDKN1A), and D11S4138 (MYOD1), and a maximum LOD score of 2.63 (P = 0.0002) was observed with D2S118. The ratios of peak torque over muscle and bone area of the midthigh of the lower contraction velocity (60 degrees/s) showed more frequently significant LOD scores than the torques at high velocity (240 degrees/s). Although myostatin is physiologically more related to muscle mass through possible effects of hyperplasia and hypertrophy than it is to strength, only two estimated muscle cross-sectional areas were marginally linked (LOD 1.06 and 1.07, P = 0.01) with marker D2S118 near GDF8 (2q32.2). The present results gave suggestive evidence that the myostatin pathway might be important for strength phenotypes, and GDF8, CDKN1A, and MYOD1 are potential candidate regions for a further and denser mapping with respect to these phenotypes.
Adolescent↗
No association between interleukin-18 gene polymorphisms and haplotypes in Dutch sarcoidosis patients.
Previously, an association between susceptibility to sarcoidosis and a polymorphism in the interleukin (IL-18) gene (IL-18 -607A/C) has been reported in Japanese. The aim of the present study was to validate this association in a clinically well-characterized population of Dutch Caucasians. Three other polymorphisms at positions -656, -137, and 1248 were included in order to extend the mapping of the IL-18 gene and to enable the construction of haplotypes. Polymorphisms were determined using sequence-specific primers (SSPs) and polymerase chain reaction (PCR). A total of 236 individuals was studied (133 patients and 103 controls). No significant differences were observed in the distribution of the -607 and the other polymorphisms between Dutch sarcoidosis patients and controls. However, significant differences in IL-18 -607 genotype and allele frequency distributions were found between the Dutch and the Japanese. From the investigated IL-18-promoter polymorphisms, we were able to deduce four haplotypes. No differences were observed in haplotype frequencies between Dutch sarcoidosis patients and controls. In conclusion, IL-18 polymorphisms do not appear to influence the susceptibility to sarcoidosis in Dutch Caucasians. Important differences in allele frequencies were observed between Japanese and Dutch sarcoidosis patients and controls.
DNA Primers↗
Pneumonia caused by Mycobacterium kansasii in a series of patients without recognised immune defect.
The clinical and epidemiological characteristics of 17 patients diagnosed with Mycobacterium kansasii pneumonia within a limited geographical region over a period of 10 years are described. An in-depth evaluation of the innate and adaptive immune systems was performed for five available patients. A comparison was made of the genetic fingerprint patterns of the isolates obtained by restriction fragment length polymorphism (RFLP) analysis, with the major polymorphic tandem repeat (MPTR) as a probe. Predisposing factors consisted of smoking, airway abnormalities, substance abuse, diabetes or poor general condition, but in two patients no risk factor was identified. In the five patients tested, no abnormalities or deficiencies were detected in the innate or adaptive type-1 immunity. All M. kansasii isolates had identical MPTR RFLP patterns, although no epidemiological connection could be established, and these were identical to those of clinical isolates from Australian patients. These data do not support the theory that defects in the innate or adaptive type-1 immunity have a role in the pathogenesis of invasive M. kansasii infections. The identical fingerprint patterns of the isolates suggested the existence of a virulent strain of M. kansasii.
Adult↗
Metal versus plastic spacers: an in vitro and in vivo comparison.
This study compared the metal Nebuchamber with the polycarbonate Volumatic spacer in vivo as well as in vitro. Seventeen asthmatic patients were evaluated in a crossover placebo-controlled double-blind study. Bronchodilation, heart rate and serum potassium levels were measured at baseline and 15 min after administration of salbutamol. Cumulative dose-response curves (200, 400, 800 and 1600 microg) were constructed. The Andersen Cascade Impactor was used to compare the aerodynamic particle size distribution. The FEV(1) measurements showed highly significant differences between placebo and the two active preparations (P<0.001), but not between the two active preparations (P=0.433). The serum potassium levels also showed highly significant differences between placebo and the two active preparations (P=0.009), but not between the two active preparations (P=0.532). Only 1600 microg salbutamol dose raised the heart rate significantly, but the difference between the two active preparations was not significant. The in vitro deposition study revealed no significant differences in the delivered dose or in the fine particle dose (P>0.05). In conclusion, there are no significant differences between the Volumatic and Nebuchamber either in vivo or in vitro.
Administration, Inhalation↗
Estimated risk of HIV transmission by blood transfusion in Kenya.
BACKGROUND: During the past decade, developing countries have received limited support for blood safety programmes. The Kenya Ministry of Health did a collaborative multicentre assessment to establish the risk of HIV transmission by transfusion in Kenya, to promote awareness of blood safety issues in this country with a mature HIV epidemic, and to identify methods to reduce the risk of HIV transmission by blood transfusion in Kenya. METHODS: For 12 weeks, from April to July 1994, we collected information and blood samples from all blood donors, and pretransfusion samples were collected from all recipients in six government hospitals in Kenya. Blood donations were collected and screened for HIV according to standard practice in the hospital laboratories. Test results at a reference laboratory were compared with those of the hospital laboratories and risk of transfusion-associated HIV transmission was calculated. FINDINGS: The prevalence of HIV among blood donors was 6.4% (120 of 1877) and varied by hospital (range 2-20%). HIV test results were available for 1290 donor-recipient pairs. Of these, 26 HIV-positive donations were given to HIV-negative patients. We estimate that 2.0% of transfusions transmitted HIV. Problems in the hospitals that contributed to transfusion risk included inconsistent refrigeration, data entry errors, equipment failure, and lack of a quality-assurance programme. INTERPRETATION: A high proportion of blood transfusions transmitted HIV in this high-prevalence area of Africa, primarily because of erroneous laboratory practices. On the basis of these results, the Kenya Ministry of Health introduced a number of practical and inexpensive interventions to improve national blood safety.
Blood Banks↗
Evaluation of a sensitive/less-sensitive testing algorithm using the 3A11-LS assay for detecting recent HIV seroconversion among individuals with HIV-1 subtype B or E infection in Thailand.
The development of a serologic algorithm to determine recent HIV seroconversion, using sensitive/less-sensitive testing strategies, has generated widespread interest in applying this approach to estimate HIV-1 incidence in various populations around the world. To evaluate this approach in non-B subtypes, longitudinal specimens (n = 522) collected from 90 incident infections among injecting drug users in Bangkok (subtype B infection, n = 18; subtype E infection, n = 72) were tested by the 3A11-LS assay. Standardized optical density (SOD) was calculated, using median values, and the window period between seroconversion as determined by sensitive and less sensitive tests was estimated by a maximum-likelihood model described previously. Our results show that the mean window period of the 3A11-LS assay was 155 days (95% CI, 128-189 days) for subtype B but was 270 days (95% CI, 187-349 days) for subtype E specimens from Thailand. About 4% of individuals with incident subtype E infections remained below the threshold (SOD of 0.75), even 2 years after seroconversion. Among the patients with clinical AIDS and declining antibodies, none of the 7 individuals with subtype B, but 10 (8.7%) of 115 with subtype E infections, were misclassified as recent infections. Lowering the cutoff to an SOD of 0.45 for subtype E specimens resulted in a mean window period of 185 days (95% CI, 154-211 days), with all individuals seroconverting, and reduced the number of subtype E-infected patients with AIDS who were misclassified as having recent infection to 2.6%. Our results demonstrate that the 3A11-LS assay has different performance characteristics in detecting recent infections among individuals infected with subtypes B or E. Determining appropriate cutoffs and mean window periods for other HIV-1 subtypes will be necessary before this approach can be reliably implemented in settings where non-B subtypes are common.
Adult↗
Pig-tailed macaques infected with human immunodeficiency virus (HIV) type 2GB122 or simian/HIV89.6p express virus in semen during primary infection: new model for genital tract shedding and transmission.
Characterizing human immunodeficiency virus (HIV) expression in semen during primary infection remains essential to understanding the risk of sexual transmission. This investigation represents the first systematic evaluation of male genital tract shedding to use a nonhuman primate model, including the impact of exposure route and viral virulence. Male macaques were inoculated with either a chronic disease-causing virus (HIV-2(GB122); n=4 intravenous; n=4 intrarectal) or an acutely pathogenic simian/HIV strain (SHIV(89.6P); n=2 intravenous). All macaques were systemically infected, and seminal plasma virion-associated RNA (vRNA) levels were approximately 10-fold lower than those in blood. In HIV-2(GB122) infection, seminal virus was delayed by 1-2 weeks compared with that in blood. Intrarectal inoculation resulted in a shorter duration of seminal vRNA expression and intermittent seminal cell provirus. No delays, higher peaks ( approximately 50-fold), or longer durations in seminal virus expression were noted for SHIV(89.6P) infection. This novel model definitively establishes that virus dissemination results in early peak seminal levels and provides a basis for evaluating interventions targeting male genital tract expression.
Animals↗
Contribution of Th1 and Th2 cells to protection and pathology in experimental models of granulomatous lung disease.
Mice that had received adoptive transfer of DO11.10 TCR transgenic T cells polarized toward a Th1 or a Th2 phenotype were challenged with Ag-coated beads or with recombinant Mycobacterium tuberculosis expressing the OVA determinant. The resulting bead-induced pulmonary granulomas reflected the phenotype of the adoptively transferred T cells, with the Th2 cells promoting a fibrotic reaction. Mice receiving Th1 cells mounted an epitope-specific protective response to challenge with recombinant M. tuberculosis. Th2 recipients were characterized by enhanced weight loss and lung fibrosis during acute high-dose infection. The combination of TCR transgenic T cells and epitope-tagged mycobacteria provides a novel experimental model for investigation of the pathogenesis of tuberculosis.
Adoptive Transfer↗
Lipoprotein access to MHC class I presentation during infection of murine macrophages with live mycobacteria.
Following uptake by macrophages, live mycobacteria initially reside within an immature phagosome that resists acidification and retains access to recycling endosomes. Glycolipids are exported from the mycobacterial phagosome and become available for immune recognition by CD1-restricted T cells. The aim of this study was to explore the possibility that lipoproteins might similarly escape from the phagosome and act as immune targets in cells infected with live mycobacteria. We have focused on a 19-kDa lipoprotein from Mycobacterium tuberculosis that was previously shown to be recognized by CD8(+) T cells. The 19-kDa Ag was found to traffic separately from live mycobacteria within infected macrophages by a pathway that was dependent on acylation of the protein. When expressed as a recombinant protein in rapid-growing mycobacteria, the 19-kDa Ag was able to deliver peptides for recognition by MHC class I-restricted T cells by a TAP-independent mechanism. Entry into the class I pathway was rapid, dependent on acylation, and could be blocked by killing the mycobacteria by heating before infection. Although the pattern of 19-kDa trafficking was similar with different mycobacterial species, preliminary experiments suggest that class I presentation is more efficient during infection with rapid-growing mycobacteria than with the slow-growing bacillus Calmette-Guérin vaccine strain.
Animals↗
Multifocal osteomyelitis caused by nontuberculous mycobacteria in patients with a genetic defect of the interferon-gamma receptor.
We describe three patients with multifocal osteomyelitis caused by Mycobacterium avium and a family history of one or more first degree family members diagnosed with various clinical presentations of infections with nontuberculous mycobacteria. There was a significant delay in the diagnosis and they had a protracted course of their illness, which responded only slowly to prolonged multi-drug treatment. In one patient, additional treatment with interferon-gamma (IFN-gamma) was necessary. Macrophages of these patients had decreased in vitro responsiveness to IFN-gamma. Genomic sequencing revealed that these patients and their affected family members were heterozygous for a previously described dominant negative mutation in the gene encoding the IFN-gamma binding receptor-1 chain. The clinical presentations of the infections with nontuberculous mycobacteria in these families, with spread limited to skin, bone and lymph nodes, is discussed in the light of the immune mechanisms that are responsible for the clearance of otherwise poorly pathogenic environmental mycobacteria.
Adult↗
Recombinant Lactobacillus plantarum inhibits house dust mite-specific T-cell responses.
Recent evidence suggests that chronic exposure to lactobacilli, which are part of the normal intestinal flora, inhibits the development of allergic disorders. Allergy is mediated by Th2 cells, which produce high levels of IL4 and IL5, and suppressive effects of lactic acid bacteria on the development of allergy have been attributed to their Th1-inducing properties. On the other hand, lactic acid bacteria have also been shown to suppress autoimmune disorders which are mediated by Th1 cells producing high levels of IFNgamma. To study this apparent discrepancy, the immunomodulatory potential of lactobacilli was evaluated using recombinants that express an immunodominant T-cell epitope of Der p 1 of house dust mites. Mucosal immunization of C57BL/6 J mice with such recombinants resulted in the induction of T cells which produced low amounts of IFNgamma. Immunization with the house dust mite peptide followed by treatment with recombinant Lactobacillus plantarum resulted in the inhibition of both IFNgamma and IL5 production. The effect on IFNgamma production was shown to be a non-specific effect of L. plantarum. The effect on IL5 production, however, was only observed when the recombinant expressing the Der p 1 peptide, but not the control recombinant, was used for treatment. Neither of the recombinants had an effect on the antibody response. Taken together, these data suggest that recombinant L. plantarum may be a suitable candidate for the treatment of allergic disorders.
Animals↗
Analysis of recombinant mycobacteria as T helper type 1 vaccines in an allergy challenge model.
The potential for development of mycobacteria as T helper type 1 (Th1) vaccines capable of induction of Th1 responses to recombinant antigens was explored in a model system based on an immunodominant peptide from house dust mite. Different recombinant mycobacterial preparations were compared for their ability to induce a Th1 response to the peptidea. It was found that mycobacterial viability was not a prerequisite for Th1 immunogenicity. A dominant interferon-gamma (IFN-gamma) response to peptide was observed in splenocytes from C57BL/6J mice immunized with live or heat-killed preparations of recombinant Mycobacterium vaccae or with live attenuated bacillus Calmette-Guèrin (BCG) vaccine expressing the antigen. Interleukin-5 (IL-5), a marker of a Th2 response, was detected only in mice receiving live M. vaccae. A similar pattern was observed in BALB/b mice, although the magnitude of the IFN-gamma response was much lower. Control and immunized mice were subsequently exposed to allergen using a Th2-inducing challenge protocol. A significant shift from a Th2 to a Th1 response was observed in immunized mice, as judged by cytokine expression by splenocytes and by subclass of circulating antibody. The effect was seen in three inbred mouse strains differing in their innate bias towards Th1 or Th2 responses. It was dependent on the presence of specific antigen in the mycobacterial preparation and, under the immunization conditions tested, was more pronounced with dead M. vaccae than with live BCG as carrier vaccine. The results demonstrate the potency of killed mycobacteria as Th1 adjuvants and suggest a potential application for recombinant mycobacteria in antigen-specific immune modulation.
Adjuvants, Immunologic↗
Mismatched wear couple zirconium oxide and aluminum oxide in total hip arthroplasty.
A patient complained about a squeaking noise in his total hip arthroplasty. Clinical evaluation revealed good function, and there were no signs of loosening on the radiograph. Physiotherapy did not alter this phenomenon, and ultimately a revision was performed 42 months after the first surgery. The analysis of the retrievals revealed that a zirconium oxide ceramic head had been paired with a monolithic alumina ceramic cup. The cup showed large deviations from an ideal sphere but minor wear signs. The head exhibited heavy local damage in the articulation zone. This damage might have been caused by the observed unsatisfactory fit between cup and ball, resulting in high stress concentrations and increased wear of the zirconium head. The characteristics of the zirconium and aluminum ceramics pairing might have worsened the process. The combination of implants used in this retrieved wear couple was never approved. To prevent such problems, components of different manufacturers should never be mixed and matched unless explicitly stated.
Aluminum Oxide↗
[Long iliac artery occlusions: Feasibility, short- and mid-term outcome].
PURPOSE: It was the aim of the following study to determine the feasibility of the recanalization of long occlusions in iliac arteries and to establish its patency rate. MATERIAL AND METHODS: We retrospectively evaluated the data of 23 patients (15 male and 8 female) with occlusions of the iliac arteries with a mean length of 12 cm (range: 9-15 cm). The occlusions were situated either in the common iliac artery (CIA) (n = 3), in the external iliac artery (EIA) (n = 12) or in both CIA and EIA (n = 7). In one patient three vessels, the common femoral artery included, were involved. The recanalization procedure was performed with wire and catheter from retrograde and, in case of a failure, from antegrade in a cross-over technique. RESULTS: Recanalization succeeded in all patients. Technical success defined as residual stenosis < 30 % was seen in 20 of 23 patients. Early reocclusions were seen in four patients, in three of whom, the stent dilatation had been incomplete. Late reocclusions were observed in three patients, one of whom had already had early reocclusion. The reason was stent breakage in one, stent dehiscence in the second and restenosis in the third patient. All of the patients with reocclusion either early or late, had received covered stents. In four patients restenosis developed within 30 months: It was successfully treated by ballon dilatation or stent. Embolism during the recanalization procedure was observed in six patients. Embolism was observed on the ipsilateral side in five, and on the contralateral side in one patient. In each patient who had experienced embolism, balloon dilatation had been performed before stent implantation. CONCLUSION: 1) There is some evidence that the recanalization of long iliac artery occlusions is feasible. 2) The main reason for early and late reocclusions is either rest stenosis or restenosis. 3) Covered stents should only be used in selected cases. 4) Primary stenting is the treatment of choice in order to prevent embolism.
Adult↗
Novel Salmonella enterica serovar Typhimurium protein that is indispensable for virulence and intracellular replication.
Upon contact with host cells, the intracellular pathogen Salmonella enterica serovar Typhimurium promotes its uptake, targeting, and survival in intracellular niches. In this process, the bacterium evades the microbicidal effector mechanisms of the macrophage, including oxygen intermediates. This study reports the phenotypic and genotypic characterization of an S. enterica serovar Typhimurium mutant that is hypersusceptible to superoxide. The susceptible phenotype is due to a MudJ insertion-inactivation of a previously undescribed Salmonella gene designated sspJ that is located between 54.4 and 64 min of the Salmonella chromosome and encodes a 392-amino-acid protein. In vivo, upon intraperitoneal injection of 10(4) to 10(7) bacteria in C3H/HeN and 10(1) to 10(4) bacteria in BALB/c mice, the mutant strain was less virulent than the wild type. Consistent with this finding, during the first hour after ingestion by macrophage-like J774 and RAW264.7 cells in vitro, the intracellular killing of the strain carrying sspJ::MudJ is enhanced fivefold over that of wild-type microorganisms. Wild-type salmonellae displayed significant intracellular replication during the first 24 h after uptake, but sspJ::MudJ mutants failed to do so. This phenotype could be restored to that of the wild type by sspJ complementation. The SspJ protein is found in the cytoplasmic membrane and periplasmic space. Amino acid sequence homology analysis did reveal a leader sequence and putative pyrroloquinoline quinone-binding domains, but no putative protein function. We excluded the possibility that SspJ is a scavenger of superoxide or has superoxide dismutase activity.
Animals↗
Peritoneal culture alters Streptococcus pneumoniae protein profiles and virulence properties.
We have examined the properties of Streptococcus pneumoniae cultured in the murine peritoneal cavity and compared its virulence-associated characteristics to those of cultures grown in vitro. Analysis of mRNA levels for specific virulence factors demonstrated a 2.8-fold increase in ply expression and a 2.2-fold increase in capA3 expression during murine peritoneal culture (MPC). Two-dimensional gels and immunoblots using convalescent-phase patient sera and murine sera revealed distinct differences in protein production in vivo (MPC). MPC-grown pneumococci adhered to A549 epithelial cell lines at levels 10-fold greater than those cultured in vitro.
Animals↗
Efficacy of postexposure prophylaxis after intravaginal exposure of pig-tailed macaques to a human-derived retrovirus (human immunodeficiency virus type 2).
Postexposure prophylaxis (PEP) after intravaginal exposure to human immunodeficiency virus (HIV) was investigated using the HIV type 2 (HIV-2)/pig-tailed macaque transmission model. PEP for 28 days with the reverse transcriptase inhibitor (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA; tenofovir) was initiated 12 to 72 h following HIV-2 exposure. Systemic infection was not evident in the 12- and 36-h groups, as defined by plasma viremia, cell-associated provirus, antibody responses, and lymph node virus. Breakthrough infection in the 72-h group was detected at week 16 post-virus exposure. These results demonstrate for the first time using a vaginal transmission model that early intervention after high-risk sexual exposures may prevent infection.
Acquired Immunodeficiency Syndrome↗