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Biomedical subjects

A Dekker

Publications and source records attributed to A Dekker.

At least 37 records · Page 2Linked to original sources
PubMed2002

Lessons from the foot and mouth disease outbreak in The Netherlands in 2001.

The Netherlands had recently developed a new strategy for the eradication of foot and mouth disease (FMD). When FMD was confirmed in Great Britain and France, recent imports of susceptible animals from these countries were traced and preventive measures were taken. On 21 March 2001, FMD was confirmed in The Netherlands. The disease was introduced by calves which became infected at a staging post in Mayenne, France, where infected sheep from Great Britain were present. A total of 26 farms were infected. Emergency vaccination of all susceptible animals was applied. Suppressive vaccination was chosen, implying that all vaccinated animals had to be slaughtered. Ring vaccination of all susceptible animals within 2 km of an infected herd was the standard procedure. However, in the 'Noord Veluwe', vaccination had to be applied to a larger area. The last affected farm was confirmed on 22 April 2001. Emergency vaccination contained the FMD infection rapidly. The last vaccinated animal was slaughtered on 25 May 2001. Many farmers were not convinced that the killing of their healthy, vaccinated animals was justified and tried to prevent the culling, but without success. Politicians and the public at large are now strongly opposed to the large-scale slaughter of vaccinated animals should a future outbreak of FMD occur. The Office International des Epizooties (OIE: World organisation for animal health) should incorporate control of vaccinated animals with non-structural protein (NSP) tests in the chapter on FMD in the International Animal Health Code.

Animals↗
PubMed2001

Cidofovir for cytomegalovirus infection and disease in allogeneic stem cell transplant recipients. The Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

A retrospective study was performed to collect information regarding efficacy and toxicity of cidofovir (CDV) in allogeneic stem cell transplant patients. Data were available on 82 patients. The indications for therapy were cytomegalovirus (CMV) disease in 20 patients, primary preemptive therapy in 24 patients, and secondary preemptive therapy in 38 patients. Of the patients, 47 had received previous antiviral therapy with ganciclovir, foscarnet, or both drugs. The dosage of CDV was 1 to 5 mg/kg per week followed by maintenance every other week in some patients. The duration of therapy ranged from 1 to 134 days (median, 22 days). All patients received probenecid and prehydration. Ten of 20 (50%) patients who were treated for CMV disease (9 of 16 with pneumonia) responded to CDV therapy, as did 25 of 38 (66%) patients who had failed or relapsed after previous preemptive therapy and 15 of 24 (62%) patients in whom CDV was used as the primary preemptive therapy. Of the patients, 21 (25.6%) developed renal toxicity that remained after cessation of therapy in 12 patients. Fifteen patients developed other toxicities that were potentially due to CDV or the concomitantly given probenecid. No toxicity was seen in 45 (61.6%) patients. Cidofovir can be considered as second-line therapy in patients with CMV disease failing previous antiviral therapy. However, additional studies are needed before CDV can be recommended for preemptive therapy.

Adolescent↗
PubMed2001

Respiratory virus infections after stem cell transplantation: a prospective study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

Community-acquired respiratory virus infections are a cause of mortality after stem cell transplantation (SCT). A prospective study was performed at 37 centers to determine their frequency and importance. Additional cases were also collected to allow the analysis of risk factors for severe infection. Forty episodes were collected in the prospective study and 53 additional episodes through subsequent case collection. The frequency of documented respiratory virus infections was 3.5% among 819 allogeneic and 0.4% among 1154 autologous SCT patients transplanted during the study period. The frequency of lower respiratory tract infections (LRTI) was 2.1% among allogeneic and 0.2% among autologous SCT patients. The mortality within 28 days from diagnosis of a respiratory viral infection was 1.1% among allogeneic SCT while no autologous SCT patient died. The deaths of five patients (0.6%) were directly attributed to a respiratory virus infection (three RSV; two influenza A). On multivariate analysis, lymphocytopenia increased the risk for LRTI (P = 0.008). Lymphocytopenia was also a significant risk factor for LRTI in patients with RSV infections. The overall mortality in RSV infection was 30.4% and the direct RSV-associated mortality was 17.4%. For influenza A virus infection, the corresponding percentages were 23.0% and 15.3%. This prospective study supports the fact that community-acquired respiratory virus infections cause transplant-related mortality after SCT.

Adolescent↗
PubMed2001

Detection of photoacoustic transients originating from microstructures in optically diffuse media such as biological tissue.

The generation and detection of broadband photoacoustic (PA) transients may be used for on-axis monitoring or for imaging of optically different structures in the interior of diffuse bodies such as biological tissue. Various piezoelectric sensors are characterized and compared in terms of sensitivity, depth response, and directivity with respect to spherical broadband acoustic pulses. The influence on the sensor output of acoustic interference and refraction of the PA transients at the sample-sensor interface is discussed. Ring detectors are suitable for deep on-axis detection thanks to their strong directional sensitivity, and small disk sensors are most suited for 3-D imaging of microstructures such as the (micro)vascular system. Voltage and charge preamplification schemes are compared in terms of the signal-to-noise ratio (SNR). In all cases, the preamplifier noise turns out to be the limiting factor for the sensitivity. Based on experimental data, for several sensor types and optical wavelengths, the theoretical detectability of PA signals generated by blood-like absorbers in biological tissue is discussed.

Acoustics↗
PubMed2000

Singleton reactors in the diagnosis of swine vesicular disease: the role of coxsackievirus B5.

Swine vesicular disease virus (SVDV) and Coxsackie B5 virus (CVB5) are closely related viruses that can infect swine and man and give rise to cross-reacting serum antibodies. It is, therefore, possible that SVD antibodies found in serologic screenings of pigs are induced by CVB5. Single positive animals found in screening programmes are generally referred to as singleton reactors (SR). To determine whether SR in SVDV screenings are induced by CVB5 infection, virus neutralisation tests (VNTs) and radioimmunoprecipitation assays (RIPA) were carried out on sera of SR, sera of pigs experimentally infected with SVDV, and sera from pigs vaccinated with CVB5 isolates. The SR sera reacted repeatedly positive in the SVDV UKG/27/72 VNT, but reacted differently in three other VNTs (SVDV NET/1/92, CVB5A, and CVB5B). The VNT titres obtained with the SR sera revealed a correlation between both SVDV strains, and also between both CVB5 stains, but no correlation was found between SVD and CVB5 VNT titres. Sera of experimentally infected (SVDV) or vaccinated (CVB5) pigs showed titres in all four neutralisation tests. In the RIPA, the reaction patterns of the SR sera varied considerably with all four antigens used, in contrast to sera from pigs experimentally infected with SVDV that reacted with all antigens used, and sera from pigs vaccinated with CVB5 that reacted only with CVB5 antigens. The results presented in this paper show that neither CVB5 nor SVDV infections are the only cause of the SR phenomenon. Testing for CVB5 specific antibodies can reduce the number of SR sera in the serodiagnosis of SVDV.

Animals↗
PubMed2000

Chimeric swine vesicular disease viruses produced by fusion PCR: a new method for epitope mapping.

A new method of epitope mapping based on chimeric swine vesicular disease (SVD) viruses produced by fusion PCR (polymerase chain reaction). Seven out of 16 neutralising and non-neutralising newly produced monoclonal antibodies (MAbs) discriminated between SVD isolate ITL/1/66 and NET/1/92. Using fusion PCR eight chimeric viruses were produced containing different supplementary pieces of the P1 region of both parent strains. Using these chimeric viruses we were able to map the epitope regions recognised by these seven neutralising and non-neutralising Mabs. This new method, using chimeric viruses produced by fusion PCR, is particularly valuable for the epitope mapping of non-neutralising MAbs.

Animals↗
PubMed2000

Dose-finding study of valspodar (PSC 833) with daunorubicin and cytarabine to reverse multidrug resistance in elderly patients with previously untreated acute myeloid leukemia.

INTRODUCTION: This trial was designed to determine the maximum tolerated dose of intravenous daunorubicin (DNR) in combination with valspodar and to test the feasibility of P-glycoprotein modulation using valspodar in elderly patients with previously untreated acute myelogenous leukemia receiving standard induction chemotherapy. METHODS: Patients > or =60 years of age with previously untreated AML received valspodar (10 mg/kg/24 h by continuous intravenous infusion [CIV] on days 1-4 with a 2-mg/kg loading dose on day 1) in conjunction with two cycles of induction chemotherapy consisting of cytarabine (200 mg/m(2) CIV on days 1-7), and DNR (35 mg/m(2) [cohort 1] or 45 mg/m(2) [cohort 2] on days 1-3, intravenous bolus). Patients were assessed for dose-limiting toxicities (DLT), response rate, event-free and overall survival, and pharmacokinetics of valspodar and DNR. RESULTS: Valspodar was well tolerated at the lower DNR dose level (ie, 35 mg/m(2)) resulting in a 21% rate of DLT and only three toxic deaths. Treatment-related mortality was unacceptably high at the 45 mg/m(2) DNR dose level. The complete response rate was 49% overall and similar in both cohorts. The median overall survival of patients was 333 days in cohort 1 compared to 98 days in cohort 2. At baseline, 70% of assessable patients were P-glycoprotein positive. CONCLUSION: Substantial inhibition of P-glycoprotein activity can be achieved in this patient population at clinically tolerable doses of valspodar and DNR. The maximum tolerated dose of DNR was established as 35 mg/m(2). This regimen is being further evaluated in phase III trials.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Swine vesicular disease, studies on pathogenesis, diagnosis, and epizootiology: a review.

Swine vesicular disease (SVD) is a contagious viral disease of swine. It causes vesicular lesions indistinguishable from those observed of foot-and-mouth disease. Infection with SVD virus (SVDV) can lead to viraemia within 1 day and can produce clinical signs 2 days after a pig has come into contact with infected pigs or a virus-contaminated environment. Virus can be detected 3.5 hours after infection using immunohistochemistry. In these in vitro studies, this technique was superior to in-situ hybridization. In SVDV-infected tissues, however, more infected cells were positive using in-situ hybridization, and these were already seen 4.5 hours after infection. For serological diagnosis of SVD several new enzyme-linked immunosorbent assays (ELISA's) have been developed. The newest ELISAs, based on monoclonal antibodies, are superior to the previous tests. The new tests produce fewer less false-negative results and enable large-scale serological screening. In screening programmes a small percentage of false positive reactors have been detected. The cause of these false-positive reactions has not been identified, though infections with human Coxsackie B5 virus can be excluded.

Animals↗
PubMed2000

Construction of a full-length infectious cDNA clone of swine vesicular disease virus strain NET/1/92 and analysis of new antigenic variants derived from it.

The Dutch swine vesicular disease virus (SVDV) isolate NET/1/92 was one of the first isolates belonging to a new SVDV antigenic group. This strain was completely sequenced and was shown to have 93% similarity with the UKG/27/72 isolate. To enable antigenicity, replication, maturation and pathogenicity studies of NET/1/92, an infectious full-length cDNA clone, designated pSVD146, was prepared. The in vitro and in vivo biological properties of the virus derived from pSVD146 were studied by analysing antigenicity, plaque morphology, growth curves and virulence in pigs. The epitopes of newly prepared monoclonal antibodies were roughly mapped by fusion-PCR. Fine mapping of epitopes at the amino acid level was achieved by introducing single amino acid mutations in pSVD146. Two new amino acids important in epitope formation were located in VP1; one was mapped in the C-terminal end and the second is thought to be located in the H-I loop. Growth curve and plaque sizes in vitro were similar between virus derived from pSVD146 and the parent wild-type virus. In virulence studies in pigs, the lesions score, neutralization titres and the seroconversion rates were comparable between virus derived from pSVD146 and the parent strain. Since virus derived from pSVD146 had the same biological properties as the parent strain NET/1/92, the full-length infectious cDNA clone pSVD146 will be very useful in studies of the antigenicity, virulence, pathogenesis, maturation and replication of SVDV.

Amino Acid Sequence↗
PubMed1999

[Foot-and-mouth disease: clinical aspects, epizootiology and diagnosis].

A description of the clinical signs, differential diagnosis, epizootiology and laboratory diagnosis of foot-and-mouth disease in ruminants and pigs is given. Clinical signs are most easily recognised in cattle and pigs. Sheep and goats with foot-and-mouth disease do not show distinct clinical signs and can easily be missed. Clinical diagnosis by the veterinary practitioner is very important in case of an outbreak of foot-and-mouth disease.

Animals↗
PubMed1999

[Foot-and-mouth disease of cattle is not a zoonosis].

In 1997 there was an outbreak of foot-and-mouth disease (FMD) among cattle in Turkey. People visiting that country were warned against importing animal products into the Netherlands. This had nothing to do with hazards to human health, as FMD virus is not a zoonotic virus, but with the risk of spread of the disease to livestock in the Netherlands, notably to cattle and pigs. A disease with similar clinical symptoms in pigs is swine vesicular disease (SVD), which is not a zoonosis either. FMD virus is an aphtovirus, SVD virus is an enterovirus. Hand-foot-and-mouth disease in humans is caused by other enteroviruses, i.e. Coxsackie virus and enterovirus 71.

Animals↗
PubMed1999

Production of recombinant human type I procollagen homotrimer in the mammary gland of transgenic mice.

The large scale production of recombinant collagen for use in biomaterials requires an efficient expression system capable of processing a large (> 400 Kd) multisubunit protein requiring post-translational modifications. To investigate whether the mammary gland of transgenic animals fulfills these requirements, transgenic mice were generated containing the alpha S1-casein mammary gland-specific promoter operatively linked to 37 Kb of the human alpha 1(I) procollagen structural gene and 3' flanking region. The frequency of transgenic lines established was 12%. High levels of soluble triple helical homotrimeric [(alpha 1)3] type I procollagen were detected (up to 8 mg/ml) exclusively in the milk of six out of 9 lines of lactating transgenic mice. The transgene-derived human procollagen chains underwent efficient assembly into a triple helical structure. Although proline or lysine hydroxylation has never been described for any milk protein, procollagen was detected with these post-translational modifications. The procollagen was stable in milk; minimal degradation was observed. These results show that the mammary gland is capable of expressing a large procollagen gene construct, efficiently assembling the individual polypeptide chains into a stable triple helix, and secreting the intact molecule into the milk.

Amino Acids↗
PubMed1998

Identification of BCAR3 by a random search for genes involved in antiestrogen resistance of human breast cancer cells.

The antiestrogen tamoxifen is important in the treatment of hormone-dependent breast cancer, although development of resistance is inevitable. To unravel the molecular mechanisms of antiestrogen resistance, a search for involved genes was initiated. Retrovirus-mediated insertional mutagenesis was applied to human ZR-75-1 breast cancer cells. Infected cells were subjected to tamoxifen selection and a panel of resistant cell clones was established. Screening for a common integration site resulted in the identification of a novel gene designated BCAR3. Transfer of this locus by cell fusion or transfection of the BCAR3 cDNA to ZR75-1 and MCF-7 cells induces antiestrogen resistance. BCAR3 represents a putative SH2 domain-containing protein and is partly homologous to the cell division cycle protein CDC48.

Amino Acid Sequence↗
PubMed1998

Validation of a monoclonal antibody-based ELISA to detect antibodies directed against swine vesicular disease virus.

A simple, rapid and sensitive competitive monoclonal antibody-based ELISA for the detection of antibodies directed against swine vesicular disease virus (SVDV) was developed. The ELISA was validated using field sera originating from SVDV-infected and non-infected Dutch pig herds, reference sera obtained from the Community Reference Laboratory for Swine Vesicular Disease at the Institute for Animal Health, Pirbright Laboratory, UK, and sera from animals infected experimentally. When testing 4277 sera originating from non-infected Dutch pig herds and collected as part of the national screening program, this ELISA had only 0.6% false positive results, whereas approximately 2% of false positive results were obtained with a conventional blocking ELISA used until recently. A sensitivity relative to the virus neutralisation test of > 97% was achieved when testing sera collected from Dutch pig farms where an outbreak of SVDV had occurred. All international reference sera scored consistently correct. Sera collected sequentially from pigs experimentally infected with SVDV isolates representing all currently recognized antigenic groups, were scored positive slightly earlier by the ELISA compared to the virus neutralisation test. This monoclonal antibody-based competitive ELISA for SVDV antibodies designated the Ceditest ELISA for SVDV-Ab, is as sensitive but more specific than the ELISA used until recently. Because sera are tested at a single dilution (1:5), incubations are carried out at room temperature and test results are available within 3 h, this ELISA is simple, easy to automate and therefore very suitable for screening large numbers of serum samples.

Animals↗
PubMed1998

Use of intravenous immune globulin in addition to antiviral therapy in the treatment of CMV gastrointestinal disease in allogeneic bone marrow transplant patients: a report from the European Group for Blood and Marrow Transplantation (EBMT). Infectious Diseases Working Party of the EBMT.

The best treatment of CMV gastrointestinal disease has been controversial, with some centers adding intravenous (i.v.) Ig to antiviral chemotherapy. The aim of this retrospective survey was to compare the outcome of antiviral chemotherapy with or without i.v. Ig. A questionnaire was sent to centers belonging to the EBMT. Thirty-three patients with CMV gastrointestinal disease were reported, 22 patients were given antiviral chemotherapy alone and 11 patients a combination of antiviral chemotherapy and i.v. Ig. Eighteen of 33 (55%) patients responded to therapy, 13 of those treated with antiviral chemotherapy alone and five (45%) of those treated with the combination (P = NS). Patients with acute GVHD of grades II-IV had significantly worse outcomes than patients with acute GVHD grades 0-I. In a Cox proportional hazards model corrected for acute GVHD there was no difference in outcome of CMV gastrointestinal disease with or without addition of Ig. Survival at 100 days after diagnosis of CMV gastrointestinal disease was 64%. There was no difference in survival in patients treated with or without i.v. Ig. The results of this retrospective survey indicate that addition of i.v. Ig to antiviral chemotherapy might not improve outcome in patients with biopsy-proven CMV gastrointestinal disease.

Adolescent↗
PubMed1998

The possible use of native foot-and-mouth disease non-structural protein 3A in a serological screening test.

ELISA's for antibodies to non-structural proteins of foot-and-mouth disease developed to date use recombinant proteins as antigens. To compare the antibody response to recombinant antigen and native antigen we developed an antigen capture ELISA for foot-and-mouth protein 3A. The concentration of 3A protein in virus cultures was significantly higher in the cell debris than in the supernatant, which made it possible to use proteins directly eluted from cells separated from virus culture using Filteraid. The antigen was trapped between one monoclonal antibody coated to the plate, and a second monoclonal antibody conjugated with horseradish peroxidase. The reaction of the second (conjugated) monoclonal antibody could be blocked by several post-infection sera. Further research has to be performed to determine whether or not this method can result in a reproducible serological test.

Animals↗