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Biomedical subjects

B Joos

Publications and source records attributed to B Joos.

At least 19 recordsLinked to original sources
PubMed2001

Quantification of in vivo replicative capacity of HIV-1 in different compartments of infected cells.

Based on a mathematical model, we analyze the dynamics of CD4+ cells, actively, latently, persistently, and defectively infected cells and plasma virus after initiation of antiretroviral therapy in 14 HIV-1-infected asymptomatic patients. By simultaneous fitting of our model to clinical data of plasma HIV-1 RNA, peripheral blood mononuclear cell (PBMC)-gag RNA, proviral DNA, and CD4+ cell counts, we estimate kinetic parameters to determine the basic reproductive rate (R0) of the virus in different infected cell compartments as a measure of the replicative capacity of the virus in vivo. We find that the basic reproductive rate is larger than 1 before treatment only in actively infected cells (mean R0(act) approximately 2.46) indicating that only in this compartment the virus can maintain an ongoing infection. In latently and persistently infected cells the basic reproductive rate is considerably smaller (R0(lat) approximately 0.03 and R0(pers) approximately 0.008, respectively) indicating that these compartments contribute little to the total basic reproductive rate and cannot maintain an ongoing infection in absence of actively infected cells.

Anti-HIV Agents↗
PubMed2001

Low metabolic rate in scorpions: implications for population biomass and cannibalism.

Scorpions are abundant in arid areas, where their population biomass may exceed that of vertebrates. Since scorpions are predators of small arthropods and feed infrequently across multi-year lifespans, a parsimonious explanation for their observed, anomalously high biomass may be a depressed metabolic rate (MR). We tested the hypothesis that scorpion MR is significantly depressed compared with that of other arthropods, and we also measured the temperature-dependence of the MR of scorpions to quantify the interaction between large seasonal variations in desert temperatures and MR and, thus, long-term metabolic expenditure. Scorpion MR increased markedly with temperature (mean Q(10)=2.97) with considerable inter-individual variation. At 25 degrees C, the MRs of scorpions from two genera were less than 24 % of those of typical terrestrial arthropods (spiders, mites, solpugids and insects) of the same mass. It is likely, therefore, that the low MR of scorpions contributes to their high biomass in arid areas. The combination of high biomass and high production efficiency associated with low MR may also favor a density-dependent "transgenerational energy storage" strategy, whereby juveniles are harvested by cannibalistic adults that may be closely related to their juvenile prey.

Animals↗
PubMed2000

Residual HIV-RNA levels persist for up to 2.5 years in peripheral blood mononuclear cells of patients on potent antiretroviral therapy.

The long-term response of 10 asymptomatic, antiretroviral therapy-naive HIV-1-infected patients to potent combination antiretroviral therapy was characterized by monitoring levels of HIV-1 RNA in plasma, peripheral blood mononuclear cells (PBMC), and lymphoid tissue using highly sensitive HIV-1 RNA assays. Although plasma viral loads were continuously suppressed to levels below 50 HIV-1 RNA copies/ml for up to 2.5 years (60-128 weeks), HIV-1 RNA was still detectable at very low levels (1 to 49 HIV-1 RNA copies/ml) in 25% of the samples. In corresponding PBMC specimens, residual HIV-RNA was detectable in as much as 91% of samples tested (1 to 420 HIV-1 RNA copies/microg total RNA). Similarly, HIV-1 RNA levels in lymphoid tissue also remained detectable at a high frequency (86%). A highly significant correlation was demonstrated between therapy-induced change in PBMC HIV-1 RNA levels and change in plasma HIV-1 RNA levels (r2 = 0.69; p = 0.003). These findings support the concept that measurement of HIV-1 RNA in the easily accessible PBMC compartment is relevant for evaluating the potency of current and future antiretroviral therapies.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Rigorous solution for the elasticity of diluted gaussian spring networks

We present a rigorous solution of the elasticity of the diluted Gaussian spring networks (DGSNs) at zero temperature. We show that the deformation of a diluted DGSN is homogeneous provided that the displacements of the particles on the boundary are homogeneous. It follows that at zero temperature the nonvanishing elastic stiffness coefficients are proportional to the hydrostatic pressure in both two and three dimensions. Follows a rigorous proof of the equivalence of the elasticity of the DGSN and the conductance of the random resistor network at zero temperature.

Journal Article↗
PubMed1997

Covalent attachment of hybridizable oligonucleotides to glass supports.

A simple, rapid, and efficient method for the covalent binding of oligonucleotides to solid glass supports was developed. Glass slides were derivatized with aminophenyl or aminopropyl silanes and 5'-succinylated target oligonucleotides were attached by carbodiimide-mediated coupling. Approximately 40 to 50% of the applied target oligonucleotides covalently bound to the derivatized glass. Hybridizations with radioactively labeled oligonucleotide probes showed that up to 90% of the attached oligonucleotides were available for hybridization. This system can conveniently be applied for studies on hybridization and detection of nucleic acids.

Base Sequence↗
PubMed1996

Energy metabolism, enzymatic flux capacities, and metabolic flux rates in flying honeybees.

Honeybees rely primarily on the oxidation of hexose sugars to provide the energy required for flight. Measurement of VCO2 (equal to VO2, because VCO2/VO2 = 1.0 during carbohydrate oxidation) during flight allowed estimation of steady-state flux rates through pathways of flight muscle energy metabolism. Comparison of Vmax values for flight muscle hexokinase, phosphofructokinase, citrate synthase, and cytochrome c oxidase with rates of carbon and O2 flux during flight reveal that these enzymes operate closer to Vmax in the flight muscles of flying honeybees than in other muscles previously studied. Possible mechanistic and evolutionary implications of these findings are discussed.

Animals↗
PubMed1996

Pharmacokinetics of antimicrobial agents in anuric patients during continuous venovenous haemofiltration.

BACKGROUND: The optimal drug dosing in anuric patients undergoing continuous haemofiltration is a difficult task. More pharmacokinetic data is needed to derive practical guidelines for dosage adjustments. METHODS: Drug elimination of various antimicrobial agents (amikacin, amoxycillin, ceftazidime, ciprofloxacin, flucloxacillin, imipenem, netilmicin, penicillin G, piperacillin, sulphamethoxazole, tobramycin, vancomycin) was studied in 24 patients with acute renal failure treated by pump-assisted continuous venovenous haemofiltration (CVVH). Concentrations of serial blood and ultrafiltrate samples were determined by HPLC or by fluorescence polarization immunoassay. Total body clearance (CL) and haemofilter clearance (CLf) rates were determined by standard model-independent equations. Data from published literature on fractions not bound to proteins (fu), non-renal drug clearance fractions (Qo), and normal clearance values (CLn) were used to derive a pharmacokinetic model, taking into account drug removal by ultrafiltration and by non-renal clearance. RESULTS: A total of 37 treatment periods was studied. Blood flow through the haemofilters was 100 ml/min resulting in an average ultrafiltrate flow rate (UFR) of 13.2 +/- 4.6 (range 3.2-22.1) ml/min. Acceptable correlations of calculated and measured haemofilter clearances and total body clearances were obtained. CONCLUSIONS: Total body clearance in anuric patients during CVVH is predictable from drug properties, which are generally known. The individual dosage requirements may be calculated by multiplying Qo + fu.UFR/CLn with the dose considered appropriate in the absence of renal impairment.

Acute Kidney Injury↗
PubMed1995

The scid mouse as an experimental model for the evaluation of anti-Pneumocystis carinii therapy.

The usefulness of scid mice bearing endogenous Pneumocystis carinii infection as a model for experimental chemotherapy was examined using standard compounds known to be effective against P. carinii. Trimethoprim/sulphamethoxazole was able to reduce pulmonary P. carinii cysts in a dose-dependent manner within the dose range studied (10/50 to 100/500 TMP/SMX mg/kg/d, bd, po, 5 days per week for 30 treatments). However, alterations in associated symptoms of infection (reduced body weight, increased lung weight, increased blood leucocytes and erythrocytes), was apparently not linearly dose-dependent. Blood and lung lavage fluid levels of sulphamethoxazole one hour post administration of trimethoprim/sulphamethoxazole was dose-dependent, but not linear with dose, and was apparently correlated to cyst reduction; trimethoprim was below the limit of detection at this time. Treatment of mice with 100/500 mg/kg/day trimethoprim/sulphamethoxazole required 2 weeks (bd for 10 days of treatment) before changes in indices of infection became significant. Pentamidine (20 mg/kg, sc, three times per week for 3 weeks) was nearly as effective as high-dose trimethoprim/sulphamethoxazole in reducing cysts, whereas lower doses were ineffective. Despite being unable to reduce pulmonary P. carinii infection, even low doses of pentamidine (6 or 2 mg/kg, sc, three times per week for 3 weeks) were able to reduce lung weights and blood leucocyte levels. This model of pulmonary P. carinii infections is amenable to chemotherapeutic intervention in an apparently dose-dependent fashion, and can be used to evaluate the capacity of compounds to eradicate P. carinii and resolve signs of infection.

Animals↗
PubMed1995

Monitoring of co-trimoxazole concentrations in serum during treatment of pneumocystis carinii pneumonia.

The purpose of this prospective randomized open trial was to investigate the impact of monitoring concentrations in serum on the efficacy and side effects of high-dose co-trimoxazole therapy. Forty consecutive patients with microscopically confirmed Pneumocystis carinii pneumonia were enrolled. Therapy was started with 5 and 25 mg of trimethoprim and sulfamethoxazole, respectively, per kg of body weight given every 6 h for 2 days and continued every 8 h either with (group A) or without (group B) monitoring and dose adjustments according to sulfamethoxazole levels in serum (target, 150 to 200 micrograms/ml) for a total of 21 days. Only 7 of 19 patients (83%). Patients who were treated for the full period and patients for whom co-trimoxazole was prematurely stopped had similar concentrations of sulfamethoxazole (157 +/- 52 versus 155 +/- 47 micrograms/ml) and trimethoprim (5.0 +/- 1.4 versus 5.6 +/- 1.0 microgram/ml). Concentrations of sulfamethoxazole and trimethoprim in group A (158 +/- 39 and 5.6 +/- 1.8 micrograms/ml, respectively) did not differ from those in group B (153 +/- 57 and 5.1 +/- 1.6 micrograms/ml, respectively), and the average daily maintenance doses for groups A (75.4 mg/kg plus 15.1 mg/kg) and B (76.4 mg/kg plus 15.3 mg/kg) were nearly identical. Although the average sulfamethoxazole concentrations were maintained within the target zone in the monitoring group (day 5, 160 +/- 44 micrograms/ml; day 10, 160 +/- 41 micrograms/ml; day 15, 168 +/- micrograms/ml; and day 21, 157 +/- 95 micrograms/ml), only 28% of the individual sulfamethoxazole levels were within the target range of 150 to 200 micrograms/ml after the dose adjustments (32% in group B without intervention). Response rates were similar in both groups. Complete response or improvement was observed in 18 of 19 (group A) and 19 of 21 (group B) patients. The method used for monitoring sulfamethoxazole levels with subsequent dose adjustment did not allow us to reliably achieve the target concentrations and did not significantly alter the incidence of side effects or the efficacy of the therapy.

AIDS-Related Complex↗
PubMed1994

Levels of dapsone and pyrimethamine in serum during once-weekly dosing for prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis.

Concentrations of dapsone, monoacetyldapsone, and pyrimethamine were determined in 36 serum samples from human immunodeficiency virus-infected patients on prophylaxis with once-weekly administration of dapsone-pyrimethamine (200 mg of dapsone-75 mg of pyrimethamine). During day 1 after ingestion, median levels of 1,038 ng of dapsone per ml and 356 ng of pyrimethamine per ml were found. During days 6 to 7, the dapsone level fell to < 20 ng/ml in five of nine serum samples, but the pyrimethamine level remained elevated (125 ng/ml). Concurrent, but separately ingested, didanosine administration did not seem to decrease the drug concentrations.

Adult↗
PubMed1991

Interactive effects of thyroxine and experimental location on running endurance, tissue masses, and enzyme activities in captive versus field-active lizards (Sceloporus undulatus).

This study investigates the effects of exogenous thyroxine (T4) on running endurance, tissue masses, and the activities of citrate synthase (CS), pyruvate kinase (PK), cytosolic alpha-glycerophosphate dehydrogenase (alpha-GPDH), and beta-hydroxyacyl Coenzyme A dehydrogenase (HOAD) in Sceloporus undulatus (eastern fence lizard). The enzymes were assayed to indicate maximal catabolic activities that support exercise. Parallel experiments were done on captive and field-active groups to determine whether responses in captive studies adequately predict responses in nature. Exogenous T4 was administered via intraperitoneal pellets. The effect of T4 on running endurance was dependent on the location of the experiment (P = 0.040) such that stamina was increased by T4 only in field-active lizards. At lower levels of biological organization, interactivity between T4 and experimental location was evident but less prevalent than at the level of the whole animal, and some location effects occurred independent of T4 treatment. Heart and kidney masses were significantly greater and total hind leg muscle mass was less in captive than in field-active lizards. Thyroxine reduced liver mass in both locations and kidney mass only in captive lizards. Mass-specific CS and alpha-GPDH in gastrocnemius muscle (mixed fiber type) and HOAD in heart were lower in captive than in field-active lizards; PK in heart and liver and alpha-GPDH in heart were higher in captive lizards. Thyroxine increased CS in liver and HOAD in heart, decreased alpha-GPDH in liver in both locations, and decreased alpha-GPDH in gastrocnemius only in captive lizards. The effects of T4 differed significantly between experimental locations in gastrocnemius muscle (T4 decreased PK only in captive lizards) and in liver (T4 increased PK in field-active lizards and decreased PK in captive lizards). The mechanistic basis of differences in stamina between captive and field-active and between placebo and T4-treated lizards is largely unexplained by the factors measured here, thus illustrating the uncertainty of predicting organismal performance from lower level measurements. Nonetheless, T4 has now been shown to have greater physiological activity in field-active than in captive Sceloporus with regard to resting and total daily metabolic rates and running endurance. The results of this study further confirm that endocrine experiments on captive animals may not predict responses in nature. Further efforts to clarify the physiological significance of seasonal variations in levels of thyroid hormones will have to involve, at least in part, invasive studies on field-active lizards.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1991

A method for the quantification of intracellular zidovudine nucleotides.

An assay to quantify the phosphorylation products of zidovudine (AZT) in peripheral blood mononuclear cells (PBMC) was developed. Extracts of PBMC were separated by high-performance liquid chromatography. Eluted AZT mono- (MP), di- (DP), and triphosphate (TP) were collected in separate portions. Treatment with alkaline phosphatase yielded equimolar amounts of AZT, which after solid-phase enrichment were assayed by radioimmunoassay. Detection limit was 0.1 pmol/10(6) PBMC for each nucleotide. Recoveries of 102%-118% were observed. AZT nucleotides were measured in samples from three patients receiving 250 mg of AZT every 12 h. Intracellular concentrations of AZT-MP after 1-2 h ranged from 0.9 to 1.4 pmol/10(6) PBMC and then declined to 0.3-1.1 pmol/10(6) PBMC after 4 h. AZT-DP and AZT-TP reached concentrations of 0.3-0.5 pmol/10(6) PBMC after 1-2 h and could not be detected after 4 h in any of the three patients. Duplicate determinations deviated by less than 20%.

Alkaline Phosphatase↗
PubMed1989

Long-term accuracy of fluorescence polarization immunoassays for gentamicin, tobramycin, netilmicin and vancomycin.

External quality control was performed during six years to determine the accuracy over time of the Abbott TDx fluorescence polarization system for assaying antibiotics. Unknown spiked serum samples of gentamicin, tobramycin, netilmicin and vancomycin were provided monthly by the British national external quality assessment scheme. Comparison of the 209 assay results with the target concentrations showed good correlations in all four assays. No significant deviations from linearity, from slope 1.0, and from intercept 0.0 were detected by regression analysis. Relative deviations were less than 10% and less than 15% for 78% and 90% of all specimens, respectively. On an average the same calibration curves could be used over a period of 19 weeks. Fluorescence polarization immunoassays provided rapid and reliable results over the entire study period.

Anti-Bacterial Agents↗
PubMed1988

[Are cephalosporins more active than penicillin G in poisoning with the deadly Amanita?].

High dose penicillin-G has been found empirically to be effective against liver cell damage in amanita mushroom poisoning. We have recently found that betalactam antibiotics inhibit eukaryotic DNA polymerase-alpha, penicillins being more active than cephalosporins, and this may explain the antagonistic effect of penicillin-G against amanitin toxicity. Preliminary experiments in liver cell cultures and in mice are summarized, as well as first clinical experience pointing to the possibility that cephalosporins may be more effective against amanita mushroom toxicity than penicillin-G.

Animals↗
PubMed1988

Identification of fluorescent glycopeptide derivatives by two consecutive high pressure liquid chromatographic procedures.

Reversed phase high pressure liquid chromatography (HPLC) was used to separate individual components of the complex glycopeptide antibiotic teicoplanin in microgram quantities with gradient elution. Each of eight different fractions was then subjected to a specific and highly sensitive HPLC method, which has been developed for the determination of teicoplanin concentrations in biological specimens. This analytical procedure includes precolumn derivatization with fluorescamine and isocratic elution. The fluorescent teicoplanin derivatives were identified by comparing their retention times in both HPLC procedures. Derivatization resulted in increased hydrophobicity and improved chromatographic separation, but the order of elution of the different compounds was not changed. The antimicrobial activity of the individual underivatized fractions correlated with their respective contents of total teicoplanin A2, whereas the pseudo-aglycone A3 appeared less active. Similar techniques have the potential to be applied to other complex glycopeptide antibiotics.

Anti-Bacterial Agents↗