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Biomedical subjects

D Van Beers

Publications and source records attributed to D Van Beers.

At least 19 recordsLinked to original sources

Antiadenovirus activities of several classes of nucleoside and nucleotide analogues.

The absence of any formally licensed antiadenovirus drugs and the increasing incidence of life-threatening adenovirus infections in immunosuppressed patients warrant the development of effective antiadenovirus compounds. A detailed study was performed on the antiadenovirus activities of several classes of nucleoside and nucleotide analogues in human embryonic lung fibroblast cells. The antiadenovirus activities were evaluated by three methods, viz., evaluating the adenoviral cytopathic effect, monitoring cell viability by a colorimetric assay, and real-time PCR quantitation of viral DNA as a direct parameter for virus replication. The most active and selective compounds were the acyclic nucleoside phosphonate analogues cidofovir, its adenine analogue (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], and the new derivative (S)-2,4-diamino-6-[3-hydroxy-2-(phosphonomethoxy)propoxy]pyrimidine [(S)-HPMPO-DAPy]; the N7-substituted acyclic derivative 2-amino-7-(1,3-dihydroxy-2-propoxymethyl)purine (S-2242); and the 2',3'-dideoxynucleoside analogues zalcitabine and alovudine. No antiadenovirus activity was observed for the antiviral drugs ribavirin, foscarnet, acyclovir, penciclovir, and brivudin, while ganciclovir displayed modest activity. However, in human osteosarcoma cells transfected with herpes simplex virus thymidine kinase, ganciclovir demonstrated highly potent antiadenovirus activity, suggesting that the efficacy of ganciclovir against adenovirus is limited by inefficient phosphorylation in adenovirus-infected cells, rather than by insufficient inhibition at the viral DNA polymerase level. Collectively, our antiviral data show that the adenovirus DNA polymerase exhibits sensitivity to a relatively broad spectrum of inhibitors and should be studied further as an antiviral target in antiadenovirus drug development programs.

Adenoviridae↗

Lower-limb hypoplasia due to intrauterine infection with herpes simplex virus type 2: possible confusion with intrauterine varicella-zoster syndrome.

A neonate with lower-limb hypoplasia, cutaneous scars, bilateral chorioretinitis, and multiple brain abnormalities is presented. Intrauterine herpes simplex virus type 2 (HSV-2) infection was established on the basis of serological testing of the mother and viral cultures of the child's cutaneous lesions, obtained soon after birth. This is, to the best of our knowledge, the first case of a patient with in utero-acquired HSV-2 infection presenting with a limb hypoplasia. It illustrates that, in addition to congenital varicella-zoster syndrome, HSV-2 infection should also be considered in patients presenting with limb hypoplasia.

Adult↗

High-risk genital papillomaviruses and degree of dysplastic changes in the cervix: a prospective study by fast multiplex polymerase chain reaction in Belgium.

The epidemiologic studies with the least selection bias do not support the hypothesis that HPV types 16 and/or 18 are strongly associated with cervical cancer. In this preliminary report, we describe our findings regarding type 16, 18, and 33 detection rates in 323 normal and 71 dysplastic or neoplastic cervical scrapes using fast multiplex PCR. This modified PCR technique has been shown to be the most sensitive, specific, and reproducible DNA detection method for large epidemiologic studies. The results indicate a high relative risk of increasingly severe cervical abnormality associated with the presence of high-risk HPV DNA. The analysis of the prevalence and age data according to CIN status by non-parametric statistic tests highlights the importance of other factors inversely correlated with age in the cervical transformation process.

Adult↗

Suppression of the inhibitory effect of denatured albumin on the polymerase chain reaction by sodium octanoate: application to routine clinical detection of hepatitis B virus at its infectivity threshold in serum.

Ten to fifteen percent of posttransfusion viral hepatitis cases are still caused by HBV despite mandatory third generation screening procedures for HBsAg. There is thus an urgent need for a simple, time-cost-effective, but very sensitive test for routine HBV DNA detection in serum. Nested-primed PCR has been shown to detect purified HBV DNA at its infectivity threshold in serum. Since this is too labor-intensive for routine testing, we assessed the efficiency of a Fast PCR procedure, of three pairs of primers, and of thirty-five simple serum pretreatments with the aim to achieve the same sensitivity level. Using ten-fold dilution in phosphate buffered saline as pretreatment and Fast PCR for 99 cycles, we were able to detect HBV DNA at the 2 x 10(3)/ml level in serum. Using either NaOH denaturation or sodium octanoate thermoprotection as pretreatment and Fast PCR for 99 cycles, we were able to detect HBV DNA at its infectivity threshold in serum, while the classical phenol/chloroform/isoamylic alcohol/isopropanol/ethanol DNA purification procedure enabled us to reach the 10 virus particles/ml level. These results suggest that denatured albumin is responsible for the well known inhibitory effect of serum proteins on Taq polymerase. Because of its simplicity and its lower risk of sample-to-sample cross-contamination, the sodium octanoate thermoprotection method was chosen for routine clinical detection of HBV in serum. The clinical usefulness of this approach is demonstrated by the results obtained with HBsAg-negative acute hepatitis B incubation sera and with anti HBe-positive chronic hepatitis B sera.

Blood Proteins↗

Prevalence of high risk genital papillomaviruses in the Belgian female population determined by fast multiplex polymerase chain reaction.

Because in situ/filter hybridisation is not sensitive enough and because classical polymerase chain reaction (PCR) protocols are generally not sufficiently reproducible and specific, there is little accurate information on the prevalence of human papillomaviruses (HPV) 16, 18, and 33 infections in women without dyskaryotic changes of the cervix. In our hands, our Fast Multiplex PCR protocol has always been the most sensitive, specific, and reproducible DNA detection assay in all the microbiological and haematological applications we attempted (Vandenvelde C, Verstraete M, Van Beers D [1990]: Journal of Virological Methods 30:215-228; Vandenvelde C, Scheen R, Corazza F, Van Beers D [1991a]: Journal of Experimental and Clinical Hematology 33:293-297; Vandenvelde C, Scheen R, Van Beers D, Fondu P [1991b]: Journal of Experimental and Clinical Hematology 30:25-29). Using this new technique, cervical scrapes from 336 Belgian women attending the cervical cancer screening clinic were examined for the presence of these three high-risk genital papillomaviruses. Positive results were confirmed using another set of HPV-specific primers. Exactly one sixth of our population was found positive for one or more of these HPVs. Types 33 and 16 were significantly more prevalent than type 18. The nonparametric statistical analysis of the data suggests that some risk factors such as particular sexual habits, that are inversely related to age, must exist.

Adult↗

Risk factors inducing the persistence of high-risk genital papillomaviruses in the normal cervix.

To evaluate the risk factors associated with persistence of human papillomaviruses (HPV) types 16, 18, and 33 in the normal cervix, a prospective study was carried out in Belgium of 323 women without cytological evidence of cervical intraepithelial neoplasia. Demographic and clinical data were obtained by interview, and HPV DNA was assayed in cervical-swab specimens using the Fast Multiplex Polymerase Chain Reaction-based screening and confirmatory tests. A multivariable linear regression model was constructed using four well-known risk factors: the use of an oral contraceptive which is either triphasic, or monophasic and containing ethynylestradiol in association with either norethysterone, or levonorgestrel, or lynestrenol, or gestoden, or estrogenic and containing estriol (P = 8 x 10(-5)), a positive history of genital herpes simplex virus (HSV) infection (P = 10(-4)), an age inferior or equal to 30 years (P = 0.012), and cigarette smoking (P = 0.020). Crude and adjusted relative risks were calculated for each HPV persistence predictor. The data and the results of the molecular biology of high-risk genital HPVs are consistent with the hypothesis that the use of an oral contraceptive containing simultaneously and continuously both a potent estrogen and a high activity progestative is necessary to enhance significantly HPV transcription. These observations are also consistent with the hypothesis that the oral contraceptives and HSV genital infection are responsible for HPV persistence in the normal cervix but not for HPV-induced cervical transformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Evaluation of a commercial enzyme immunomembrane filter assay for detection of respiratory syncytial virus in clinical specimens.

A commercial enzyme immunomembrane filter assay (EIFA) for respiratory syncytial virus (RSV) was compared prospectively with isolation in cell culture and an enzyme immunoassay. A total of 595 respiratory specimens, mostly from pediatric patients, were examined. The EIFA was 70.96% sensitive and 72.40% specific in comparison with cell culture. Results for 40 specimens (6.72%) were uninterpretable, mainly due to filtration difficulties. Twenty-one (25%) of 84 specimens whose results were initially considered false-positive were subsequently confirmed positive after a blocking test with bovine anti-RSV serum. On the basis of the total number of confirmed positive results, the sensitivity and the specificity of the test were 87.90% and 75.77%, respectively.

Cells, Cultured↗

Fast PCR based therapeutic follow-up of T-cell malignancies.

Available methods for the detection of minimal residual disease in T-cell malignancies are limited by their poor sensitivity and/or by their complexity. With the aim of avoiding these drawbacks, we used the Fast PCR technique in order to amplify V delta 1-(D delta 1)-(D delta 2)-J delta 1 and V gamma I family-J gamma junctional sequences from nucleated cells of boiled bone marrow. We were thus able to detect malignant T-cells down to a dilution of 1 in 665 nucleated marrow cells, in less than 4 hours after sampling. This new quantitative method is promising for monitoring therapy and detecting early disease relapse in T-lymphoproliferative disease, since it is 2 to 35 fold more sensitive than Southern blotting.

Base Sequence↗

Fast PCR-based quantitative detection of B-cell malignancies.

Available methods for the detection of minimal residual disease in hematologic malignancies are limited by their poor sensitivity and/or complexity. In order to avoid these drawbacks, we used the fast PCR technique to amplify the hypervariable chain-determining region 3 (CDR 3) of the human immunoglobulin heavy-chain gene in boiled marrow nucleated cells. This enabled us to detect malignant B-cells down to a dilution of 1 in 1,300 marrow nucleated cells within 7 hours of sampling. This new quantitative method should be useful for monitoring therapy and detecting early disease relapse in B-lymphoproliferative disease since it is 10 to 60 times as sensitive as Southern blotting.

B-Lymphocytes↗

Fast Multiplex polymerase chain reaction on boiled clinical samples for rapid viral diagnosis.

An assessment of optimal conditions for rapid simultaneous amplification of multiple human papillomavirus (HPV) sequences has been made using Thermus aquaticus DNA polymerase. All variables of practical value were studied by amplifying known target-sequences from ten-fold dilutions of well characterized cell lines. In our hands, Fast Multiplex PCR (FM-PCR), the technique of running multiple PCR reactions simultaneously with minimum incubation time at each temperature, was highly sensitive (amplification factor = 5 x 10(9) after 50 cycles), specific (100%) and reproducible (100%) for several microbiological applications. Diagnosis was generally obtained in less than 5 h after sampling. The results show that, after optimization of assay conditions, efficiency and specificity of Multiplex PCR depends exclusively on the primers design and concentration of the primers.

Base Sequence↗

Legionellosis and "torsades de pointes".

Myocarditis, pericarditis and endocarditis are rare manifestations of Legionella pneumophila infection. We describe a case of myocarditis complicated with a potentially fatal arrhythmia: "torsades de pointes".

Aged↗

Left atrial myxoma associated with systemic AA amyloidosis.

A 76-year-old woman presenting with generalized amyloidosis of the AA-type protein was found to have a left atrial myxoma. Retrospective estimation of the concentration of SAA protein, a serum precursor of AA amyloid, before and after surgical removal of the myxoma, showed that the SAA protein had disappeared after the operation. A common manifestation of myxoma is the development of a severe inflammatory syndrome that sometimes simulates rheumatic fever or bacterial endocarditis. However, to our knowledge, it has never been described in association with amyloidosis. We suggest that atrial myxoma should be added the list of neoplastic and inflammatory diseases predisposing to AA amyloidosis.

Aged↗