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J Verhoef

Publications and source records attributed to J Verhoef.

At least 361 records · Page 20Linked to original sources
PubMed1990

Discrimination by rabbit anti-idiotypic antibodies of two murine IgM monoclonal antibodies directed against lipid A.

Two murine IgM monoclonal antibodies (MAs) directed against the lipid A portion of bacterial lipopolysaccharide (LPS) were compared in their binding to Re LPS and lipid A and their idiotypic make-up with rabbit anti-idiotypic sera. Horseradish peroxidase (HRPO)-labelled MAs 8-2 and 26-20 bound equally well to Re LPS. The binding of HRPO-labelled MA 8-2 to synthetic lipid A was low compared to the relatively strong binding of labelled 26-20. The MAs proved to be competitive in a competition binding assay (CBA) with Re LPS as coating antigen. Rabbit immune sera were raised against individual MAs. Anti-idiotypic antibodies (anti-id Abs) were detected with two sensitive enzyme immunoassays (EIA): a solid-phase EIA and an inhibition EIA. The rabbit antisera proved to be idiotype specific, indicating that both MAs recognize separate epitopes. We expect that anti-id Abs will prove to be of value for the differentiation of panels of LPS specific MAs.

Animals↗
PubMed1990

Mechanism of protection of alveolar type II cells against paraquat-induced cytotoxicity by deferoxamine.

Paraquat toxicity has been associated with the generation of free radicals in alveolar epithelial cells in which paraquat specifically accumulates via a polyamine uptake system. In the present study we investigated whether deferoxamine (DF), an iron chelator that has antioxidant capacity and that also has a polyamine-like structure, could protect alveolar type II cells (ATTC) against injury by paraquat. Radiolabeled [3H]adenine ATTC were incubated in a medium containing 75 microM paraquat in the absence or presence of DF (500 microM). After 3 hr of incubation paraquat-mediated cytotoxicity of ATTC, as measured by [3H]adenine release, was significantly (P less than 0.005) decreased by addition of DF (26.6 +/- 2.6% vs 7.4 +/- 1.7%). Accumulation of radiolabeled [14C]paraquat at a concentration of 75 microM was also decreased (70%) by 500 microM DF from 94.8 +/- 2.1 to 28.9 +/- 6.7 nmoles paraquat/2.5 x 10(5) ATTC. This effect of DF was dose dependent and comparable with the protective effect of equimolar concentrations of putrescine. However, per cent uptake of paraquat at a concentration of 500 microM was not significantly inhibited by DF (1 mM), whereas paraquat-induced injury was still markedly reduced (36.2 +/- 2.5% vs 2.6 +/- 4.2%). This indicated that the protective effect of DF could not be explained by its competition with paraquat on uptake alone. In the same series of experiments using another iron chelator, pyridoxal benzoyl hydrazone (PBH), which has antioxidant properties similar to DF but does not show its polyamine-like structure, ATTC lysis was also prevented although paraquat uptake was not reduced. These in vitro data indicate that the mechanism of protection by DF against paraquat toxicity in lung epithelial type II cells is two-fold: inhibition of paraquat uptake through its compliance with the structural requirements necessary for transport, and inhibition of paraquat-induced iron-catalysed free radical generation.

Animals↗
PubMed1990

Uncoupling of oxidative and non-oxidative mechanisms in human granulocyte-mediated cytotoxicity: use of cytoplasts and cells from chronic granulomatous disease patient.

Human polymorphonuclear leukocytes (PMN) and granule-free cytoplasts were compared for their cytotoxic capacities against red blood cells (RBC) and K562 tumor cells. Phorbol myristate acetate (PMA) stimulated PMN to efficient lysis of RBC targets, while cytotoxicity against the tumor cell line K562 was moderate. Activated cytoplasts also lysed RBC targets but were not able to kill K562 tumor cells, even at high cell numbers. Suppression of the glutathione redox cycle of the K562 tumor targets markedly increased their susceptibility to lysis by PMA-activated PMN. Despite the enhanced susceptibility of antioxidant-depleted K562 tumor cells to oxygen radical-induced damage, PMA-stimulated cytoplasts did not kill these targets. Addition of exogenous myeloperoxidase or lactoferrin to cytoplasts devoid of granule did not improve the lysis of RBC and K562 tumor cells. Coating K562 targets with specific antibodies induced efficient PMN-mediated killing in comparison to PMA-stimulated lysis of non-coated targets. Cytoplasts, however, did not kill antibody-coated K562 tumor cells; this was not improved by glutathione depletion but showed some lysis of antibody-coated RBC. PMN from a patient with chronic granulomatous disease (CGD) showed normal antibody-dependent cell-mediated cytotoxicity (ADCC) against K562 tumor cells but were not able to lyse these targets after PMA stimulation. The analysis of target cell killing by cytoplasts and PMN from a CGD patient indicated that granular constituents are important mediators in the killing of nucleated target cells and that PMN-mediated ADCC does not require the release of reactive oxygen species. Differences in the susceptibility of target cells to oxygen-mediated lysis indicates that target cell antioxidant mechanisms play an important role in the outcome of the cytotoxic response.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

A probe for the detection of methicillin-resistant Staphylococcus aureus.

An approximately 300 base pair DNA fragment for use as a probe was isolated from methicillin-resistant Staphylococcus aureus DNA partially digested with Sau3AI. This probe hybridized with 25 methicillin-resistant clinical isolates of Staphylococcus aureus belonging to 18 different phage types, but not with 41 clinical isolates susceptible to methicillin.

DNA Fingerprinting↗
PubMed1990

Adherence of peritonitis-causing staphylococci to human peritoneal mesothelial cell monolayers.

The adherence of staphylococci to monolayers of human mesothelial cells was studied. Adherence of Staphylococcus aureus to mesothelial cell monolayers was 3.4-fold better than to plastic (P less than .01) whereas that of Staphylococcus epidermidis was 3.0-fold less than to plastic (P less than .01). Neither serum albumin nor gelatin inhibited staphylococcal binding. S. aureus adherence correlated with the amount of cell wall protein A (r = .63, P less than .05) but not with fibronectin binding; it was significantly inhibited by the addition of purified cell wall lipoteichoic acid (55% +/- 2.7%), teichoic acid (34.5% +/- 3.4%), and protein A (25.6% +/- 2.9%) but not peptidoglycan. Protein A- and teichoic acid-deficient mutants adhered less well than their parent strains, and encapsulated S. epidermidis adhere well to human monothelial cells. Staphylococcal binding may involve cell wall lipoteichoic acid, teichoic acid, and protein A.

Bacterial Adhesion↗
PubMed1990

Prognostic values of tumor necrosis factor/cachectin, interleukin-1, interferon-alpha, and interferon-gamma in the serum of patients with septic shock. Swiss-Dutch J5 Immunoglobulin Study Group.

Serum concentrations of immunoreactive tumor necrosis factor/cachectin (TNF), interleukin-1 beta (IL-1 beta), interferon-gamma (IFN gamma), and interferon-alpha (IFN alpha) were prospectively measured in 70 patients with septic shock to determine their evolution and prognostic values. In a univariate analysis, levels of TNF (P = .002) and IL-1 beta (P = .05) were associated with the patient's outcome, but not IFN alpha (P = .15) and IFN gamma (P = .26). In contrast, in a stepwise logistic regression analysis, the severity of the underlying disease (P = .01), the age of the patient (P = .02), the documentation of infection (nonbacteremic infections vs. bacteremias, P = .03), the urine output (P = .04), and the arterial pH (P = .05) contributed more significantly to prediction of patient outcome than the serum levels of TNF (P = .07). After 10 days, the median concentration of TNF was undetectable (less than 100 pg/ml) in the survivors, whereas it remained elevated (305 pg/ml, P = .002) in the nonsurvivors. Thus, in patients with septic shock due to various gram-negative bacteria, other parameters than the absolute serum concentration of immunoreactive TNF contributed significantly to the prediction of outcome.

Adolescent↗
PubMed1990

Effect of clindamycin on the intracellular bactericidal capacity of human peritoneal macrophages.

Survival and growth of bacteria within peritoneal macrophages has been implicated as a cause of recurrence and relapse of Staphylococcus epidermidis peritonitis during peritoneal dialysis. We studied the effect of orally administered clindamycin (known to enter and concentrate in phagocytes) on the intracellular killing of S. epidermidis by human peritoneal macrophages. Clindamycin (300 mg qid) was taken for one day by eight CAPD patients. Peritoneal macrophages were isolated from the effluents and their capacity to phagocytose and kill S. epidermidis was measured. In effluents containing clindamycin, the macrophages showed better uptake (32 vs 17%, P less than 0.01) and intracellular killing (70 vs 42%, P less than 0.01) of S. epidermidis compared with control after 1 h incubation. After 18 h S. epidermidis within peritoneal macrophages incubated with clindamycin, showed a further decrease in viability (-0.33 decrease in log cfu/ml). In contrast, control phagocytes allowed numbers of S. epidermidis to increase over 18 h (+1.46 increase in log cfu/ml; P less than 0.01 compared to clindamycin). Antibiotics with the ability to suppress intracellular bacterial growth should be studied for treatment of CAPD-related S. epidermidis peritonitis.

Clindamycin↗
PubMed1990

Transient immunodepression.

Depression of the immune system frequently occurs in the neonatal period, in old age, during pregnancy, transiently after surgery, in viral infections, in malnutrition and during 'stress'. The observed changes in immunological indices and the evidence that these may lead to clinical infection on occasion are reviewed.

Aged↗
PubMed1990

A double-blind comparison of low-dose ofloxacin and amoxycillin/clavulanic acid in acute exacerbations of chronic bronchitis.

The efficacy and safety of ofloxacin 400 mg once daily and amoxycillin/clavulanic acid 500/125 mg three times daily were compared in a double-blind manner in patients with an acute exacerbation of chronic bronchitis. Of 102 patients enrolled, 95 (93%) could be assessed for effectiveness. Treatment success was achieved in 41 (84%) of 49 patients in the ofloxacin group compared with 41 (89%) of 46 patients in the amoxycillin/clavulanic acid group. One patient who received ofloxacin and four patients in the amoxycillin/clavulanic acid group stopped medication because of unacceptable side effects. Microbiological results were evaluable in 47% of the patients. Predominant initial pathogens were Haemophilus influenzae, Streptococcus pneumoniae, sometimes in combination, and less frequently Branhamella catarrhalis. In two patients with clinical failure, randomized to ofloxacin, the initial pneumococcal strains persisted in the sputum after treatment.

Amoxicillin↗
PubMed1990

Degradation of herpes simplex virions by human polymorphonuclear leukocytes and monocytes.

The degradation of herpes simplex virus particles after uptake by phagocytes was studied, but, since lysis of the phagocyte also resulted in damage to the viral envelope, measurement of viral infectivity as a criterion of viral degradation after phagocytosis was not possible. Therefore we focused on later events in viral destruction, namely the degradation of macromolecules. We have demonstrated that polymorphonuclear leukocytes (PMN) and monocytes (MN) can rapidly degrade the membrane proteins of the phagocytosed herpes-virus virions. PMN and MN from a patient with chronic granulomatous disease showed a similar rate of degradation compared to PMN and MN from healthy donors, which excludes an important role for toxic oxygen species in viral protein degradation. Experiments using toxic oxygen species-generating systems supported this observation. In contrast to PMN, MN are also effective in the digestion of viral DNA. We conclude that PMN and MN are able to neutralize large amounts of phagocytosed HSV, so their role in antiviral defence has again been demonstrated.

DNA, Viral↗
PubMed1990

Influence of complement on sperm motility.

Isolated sperm from normo-, oligo- and astheno-spermic men were incubated for 20 h in medium supplemented with 8% heat-inactivated or untreated human serum, and in medium with heated or untreated serum deficient in complement factor C3. Before and after incubation, sperm motility was assessed by means of a computer-assisted semen analyser. The results did not show significant differences between the motility of sperm incubated in heated or untreated serum. It is concluded that heating of homologous serum is not necessary for preserving sperm motility and in some cases may even be disadvantageous.

Blood↗
PubMed1990

Pharmacokinetics of cefepime in patients with respiratory tract infections.

The steady-state pharmacokinetics of cefepime were evaluated in 10 middle-aged and elderly patients with acute lower respiratory tract infections who were receiving 1 g intravenously every 12 h. One preinfusion and 15 postinfusion serum samples and total urine output were collected over one dosing interval between days 3 and 8 of therapy. Cefepime concentrations in serum over time exhibited a multicompartmental profile. Peak and trough concentrations in serum determined by a validated high-performance liquid chromatography method were 71.2 +/- 17.2 (mean +/- standard deviation) and 6.0 +/- 4.9 mg/liter, respectively. The steady-state volume of distribution was 0.22 +/- 0.05 liter/kg. Elimination half-lives ranged from 1.93 to 6.04 h (3.92 +/- 1.28 h), and total body clearances ranged from 36.9 to 102 ml/min per 1.73 m2 (73.0 +/- 19.7 ml/min per 1.73 m2). The disposition of cefepime at steady state in patients was comparable to previous observations in healthy elderly volunteers. The predictive performance of regression equations derived from single-dose studies in volunteers relating creatinine clearance with total body and renal clearances of cefepime exhibited slight biases (mean predictive errors, -9.7 and 2.1 ml/min per 1.73 m2, respectively) and similar precisions. Predicted and observed total body clearances (63.3 +/- 25.1 versus 73.0 +/- 19.7 ml/min per 1.73 m2, respectively) and renal clearances (51.3 +/- 24.4 versus 49.3 +/- 19.6 ml/min per 1.73 m2, respectively) were not significantly different. The pharmacokinetics of cefepime in infected patients appeared to be unaltered by illness, and the steady-state disposition of cefepime was predictable from data derived from single-dose studies in volunteers.

Aged↗
PubMed1990

Intraprostatic distribution of lomefloxacin following multiple-dose administration.

The ability of lomefloxacin to penetrate and distribute within the human prostate was assessed in 20 patients undergoing elective prostate surgery (18 transurethral prostatic resections and 2 prostatectomies). Subjects were middle-aged to elderly (mean age +/- standard deviation, 69.8 +/- 8.2 years) with normal hepatic function and with creatinine clearances ranging from 35.8 to 141 ml/min/1.73 m2. Lomefloxacin was administered in 400-mg doses orally every 24 h. Its disposition was characterized following the third dose by obtaining multiple serum samples and intraoperative paired central zone and peripheral zone prostate tissue samples. Lomefloxacin concentrations were determined by a validated high-performance liquid chromatography method with fluorescence detection. Concentrations in serum during the perioperative period declined from 3.1 +/- 1.0 mg/liter (mean +/- standard deviation) at 1 h postdose to 2.3 +/- 0.7 mg/liter at 6 h postdose. The time of tissue extraction ranged from 0.1 to 7.1 h postdose. Intraoperative serum lomefloxacin concentrations ranged from 0.5 to 4.8 (median, 2.4) mg/liter, while prostate tissue concentrations ranged from 1.1 to 10.1 (median, 5.4) mg/kg of tissue for the central zone and 0.9 to 6.5 (median, 5.2) mg/kg for the peripheral zone. Intraindividual paired prostate concentrations (central zone versus peripheral zone) were not statistically different. The partition coefficient (ratio of concentration in prostate to concentration in serum) for the central zone was 2.2 +/- 0.6 (range, 1.2 to 3.1), and for the peripheral zone it was 2.1 +/- 0.7 (range, 1.2 to 4.2). Lomefloxacin exhibited good penetration into the human prostate with homogeneous intraprostatic distribution following multiple-dose administration.

4-Quinolones↗
PubMed1990

Enhanced phagocytosis of encapsulated Escherichia coli strains after exposure to sub-MICs of antibiotics is correlated to changes of the bacterial cell surface.

The influence of five antibiotics (netilmicin, ceftriaxone, cefepime, fleroxacin, and ciprofloxacin) on capsular polysaccharide distribution and on opsonophagocytosis by human polymorphonuclear leukocytes of unencapsulated and encapsulated Escherichia coli strains was studied. Unencapsulated E. coli strains were readily opsonized in serum and easily ingested by polymorphonuclear leukocytes, and antibiotics did not further enhance the phagocytosis rates. In contrast, encapsulated bacteria were poorly opsonized in human serum, and phagocytosis was enhanced after overnight exposure to 0.5x the MICs of the antibiotics, with the exception of cefepime. Incubation of unencapsulated as well as encapsulated bacteria in complement-inactivated serum markedly reduced the bacterial uptake by polymorphonuclear leukocytes regardless of the presence of antibiotics. Slide agglutination assays, performed either with a monoclonal antibody for capsular polysaccharide or with an antiserum raised against the stable unencapsulated mutant E. coli O7:K-, showed reduction but not lack of the capsular polysaccharide of encapsulated E. coli O7:K1, and better exposure of subcapsular epitopes, after incubation with 0.5x the MICs of antibiotics. Flow cytometric analysis of encapsulated E. coli exposed to netilmicin, ciprofloxacin, and fleroxacin revealed that the reduction in capsular material was homogeneous among the bacterial population. Treatment with cefepime and ceftriaxone induced two populations of bacteria that differed in the amount of K antigen present. These results indicate that sub-MICs of netilmicin, ceftriaxone, fleroxacin, and ciprofloxacin influenced complement-mediated opsonization, probably due to changes in the capsular polysaccharide structure.

Agglutination Tests↗
PubMed1990

Double-blind, dose-range-finding study of fleroxacin (RO 23-6240; AM-833) for treatment of complicated urinary tract infections.

In a double-blind randomized trial, we evaluated the efficacy and safety of three oral dosage regimens of fleroxacin, a new fluoroquinolone, once daily in 62 patients for the treatment of complicated urinary tract infections. The regimens compared were 200 mg for 10 days (n = 20), 400 mg for 10 days (n = 21), and 600 mg for 10 days (n = 21). Forty-five patients were evaluable for efficacy. A clinical cure was reached in 78% of the patients. Overall, a favorable bacteriological response (negative culture or reinfection at 4 to 6 weeks) was obtained in 36 of 45 (80%) patients. No significant difference could be found among the three dosage groups. During therapy, one Klebsiella ozaenae strain became resistant and one Pseudomonas aeruginosa strain became less susceptible to fleroxacin. In 13 patients, therapy had to be discontinued due to major adverse events (oliguria [n = 1], psychosis [n = 1], photosensitivity [n = 1], insomnia [n = 1], and nausea [n = 9]). Minor side effects were seen in 13 other patients. Increased dosage correlated significantly (P less than 0.01) with total number of adverse events.

Adult↗
PubMed1990

Bacterial iron enhances oxygen radical-mediated killing of Staphylococcus aureus by phagocytes.

It has been shown that increasing bacterial iron concentration enhances killing by hydrogen peroxide (H2O2) but not by polymorphonuclear granulocytes (PMN). It is possible that owing to the multiple bactericidal mechanisms of the PMN, differences in the killing rate of iron-loaded bacteria and control bacteria are obscured. We decided, therefore, to compare the killing of iron-loaded bacteria with that of control bacteria using human monocytes (MN), PMN, and PMN-derived cytoplasts. Incubation of Staphylococcus aureus with increasing concentrations of ferrous ammonium sulfate (0 to 1,000 microM) progressively increased the iron content in the bacteria (from 0.01 to 0.24 mumol of iron per 10(9) bacteria). Iron loading of the bacteria markedly increased their susceptibility to killing by H2O2. After 1 h of incubation with 1 mM H2O2, 95 +/- 2% of the iron-loaded bacteria were killed compared with 18 +/- 4% of the control bacteria (P less than 0.0001). Iron loading of bacteria did not alter their susceptibility to killing by human PMN. However, iron-loaded bacteria were more susceptible to killing by MN (after 12 min of incubation, 81 +/- 2 versus 74 +/- 2% killing; P less than 0.008) and to killing by PMN-derived cytoplasts (after 60 min of incubation, 52 +/- 8 versus 33 +/- 5%; P = 0.003) than the controls. Moreover, iron loading enhanced luminol-mediated chemiluminescence of MN, PMN, and PMN-derived cytoplasts. The hydroxyl radical scavenger thiourea inhibited H2O2-mediated killing of iron-loaded staphylococci as well as luminol-mediated chemiluminescence. These results suggest that alterations in intrinsic iron content increase killing of staphylococci by H2O2, MN, and PMN-derived cytoplasts by a free radical-mediated mechanism.

Blood Bactericidal Activity↗