D. Pajkrt - Academia.edu (original) (raw)

Papers by D. Pajkrt

Abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy, Jan 16, 1996

BMC Pediatrics, 2021

Background Fatigue is common among adults living with human immunodeficiency virus (HIV) as well ... more Background Fatigue is common among adults living with human immunodeficiency virus (HIV) as well as children with a chronic disease (CCD). Fatigue can have disastrous effects on health status, including health related quality of life (HRQOL). Even so, fatigue is underexplored in children and adolescents perinatally infected with HIV (PHIV+) in the Netherlands. The objective of this observational study is to explore fatigue in PHIV+ and its association with their HRQOL. Methods We measured HRQOL and fatigue using the Pediatric Quality of Life Inventory™ (PedsQL 4.0) and the PedsQL Multidimensional Fatigue Scale (MFS). The PedsQL MFS encompasses three subscales: general fatigue, sleep/rest fatigue and cognitive fatigue, and a total fatigue score. We compared outcomes of PHIV+ children and adolescents in the Amsterdam University Medical Centre with three groups: 1) HIV-uninfected controls (HIV-) matched for age, sex, region of birth, socioeconomic status and adoption status, 2) CCD, an...

Pediatric Infectious Disease Journal, 2020

Background: Limited data are available on childhood encephalitis. Our study aimed to increase ins... more Background: Limited data are available on childhood encephalitis. Our study aimed to increase insight on clinical presentation, etiology, and clinical outcome of children with severe encephalitis in the Netherlands. Methods: We identified patients through the Dutch Pediatric Intensive Care Evaluation database and included children diagnosed with encephalitis <18 years of age admitted to 1 of the 8 pediatric intensive care units (PICU) in the Netherlands between January 2003 and December 2013. We analyzed demographic characteristics, clinical symptoms, neurologic imaging, etiology, treatment and mortality. Results: We included 121 children with a median age of 4.6 years (IQR 1.3-9.8). The most frequently described clinical features were headache (82.1%), decreased consciousness (79.8%) and seizures (69.8%). In 44.6% of the children, no causative agent was identified. Viral-and immune-mediated encephalitis were diagnosed in 33.1% and 10.7% of the patients. A herpes simplex virus infection (13.2%) was mainly seen in children <5 years of age, median age, 1.73 years (IQR 0.77-5.01), while immune-mediated encephalitis mostly affected older children, median age of 10.4 years (IQR, 3.72-14.18). An age of ≥ 5 years at initial presentation was associated with a lower mortality (OR 0.2 [CI 0.08-0.78]). The detection of a bacterial (OR 9.4 [CI 2.18-40.46]) or viral (OR 3.7 [CI 1.16-11.73]) pathogen was associated with a higher mortality. Conclusions: In almost half of the Dutch children presenting with severe encephalitis, a causative pathogen could not be identified, underlining the need for enhancement of microbiologic diagnostics. The detection of a bacterial or viral pathogen was associated with a higher mortality.

Scientific Reports

Airway organoids are polarized 3D epithelial structures that recapitulate the organization and ma... more Airway organoids are polarized 3D epithelial structures that recapitulate the organization and many of the key functions of the in vivo tissue. They present an attractive model that can overcome some of the limitations of traditional 2D and Air–Liquid Interface (ALI) models, yet the limited accessibility of the organoids’ apical side has hindered their applications in studies focusing on host–pathogen interactions. Here, we describe a scalable, fast and efficient way to generate airway organoids with the apical side externally exposed. These apical-out airway organoids are generated in an Extracellular Matrix (ECM)-free environment from 2D-expanded bronchial epithelial cells and differentiated in suspension to develop uniformly-sized organoid cultures with robust ciliogenesis. Differentiated apical-out airway organoids are susceptible to infection with common respiratory viruses and show varying responses upon treatment with antivirals. In addition to the ease of apical accessibilit...

Vaccines

SARS-CoV-2-specific antibodies are secreted into human milk of infected or vaccinated lactating w... more SARS-CoV-2-specific antibodies are secreted into human milk of infected or vaccinated lactating women and might provide protection to the breastfed infant against COVID-19. Differences in antibody response after these types of exposure are unknown. In this longitudinal cohort study, we compared the antibody response in human milk following SARS-CoV-2 vaccination or infection. We analyzed 448 human milk samples of 28 lactating women vaccinated with the SARS-CoV-2 vaccine BNT162b2 as well as 82 human milk samples of 18 lactating women with a prior SARS-CoV-2 infection. The levels of SARS-CoV-2-specific IgA in human milk were determined over a period of 70 days both after vaccination and infection. The amount of SARS-CoV-2-specific IgA in human milk was similar after SARS-CoV-2 vaccination and infection. After infection, the variability in IgA levels was higher than after vaccination. Two participants with detectable IgA prior to vaccination were analyzed separately and showed higher I...

Science, 2022

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine i... more We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virul...

Blood, 1998

Evidence of factor XI (FXI) activation in vivo is scarce. In addition, it remains uncertain wheth... more Evidence of factor XI (FXI) activation in vivo is scarce. In addition, it remains uncertain whether thrombin, factor XIIa (FXIIa), or perhaps another protease is responsible for FXI conversion. We investigated the activation of FXI in eight healthy volunteers after infusion of a low dose of endotoxin (4 ng/kg of body weight). Activation of prekallikrein FXII, FXI, and prothrombin was measured with sensitive enzyme-linked immunosorbent assays (ELISAs), and FXI activation was measured with a novel enzyme capture assay that detects noncomplexed FXIa. Activation of FXI was apparent with a significant plasma peak level of noncomplexed FXIa of 10 to 11 pmol/L at 1 and 2 hours after endotoxin infusion, followed by a gradual increase in FXIa-FXIa inhibitor complexes, measured in the ELISAs, with a summit of 11 to 15 pmol/L at 6 and 24 hours, respectively. In accordance with previous studies, thrombin generation was detected 1 hour after endotoxin infusion to become maximal after 3 to 4 hour...

Innate Immunity, 1997

Erythrocytes have been suggested to bind chemokines, thus limiting their effective concentration ... more Erythrocytes have been suggested to bind chemokines, thus limiting their effective concentration in the circulation. We investigated binding of the chemokines IL-8 and RANTES to erythrocytes following endotoxin challenge. Endotoxin caused a transient increase of IL-8 in plasma, and a gradual increase of erythrocyte-bound IL-8, remaining elevated for at least 24 h in vivo. Binding of IL-8 to erythrocytes was confirmed by incubation of freshly isolated erythrocytes with endotoxin stimulated plasma. Incubation for 1 h led to a decrease in plasma concentrations of IL-8 with a concomitant increase in erythrocyte-bound IL-8 levels. Erythrocyte-bound RANTES was induced early following endotoxin infusion and our data may suggest competition between the two chemokines for the same binding site on erythrocytes in vivo. In conclusion, in humans, both IL-8 and RANTES are induced by endotoxin and are, at least in part, cleared from the plasma by binding to erythrocytes.

The Pediatric Infectious Disease Journal, 2010

(NYSDOH) is a reference diagnostic laboratory for the fungal diseases. The laboratory services in... more (NYSDOH) is a reference diagnostic laboratory for the fungal diseases. The laboratory services include testing for the dimorphic pathogenic fungi, unusual molds and yeasts pathogens, antifungal susceptibility testing including tests with research protocols, molecular tests including rapid identification and strain typing, outbreak and pseudo-outbreak investigations, laboratory contamination and accident investigations and related environmental surveys. The Fungal Culture Collection of the Mycology Laboratory is an important resource for high quality cultures used in the proficiency-testing program and for the in-house development and standardization of new diagnostic tests. Mycology Proficiency Testing Program provides technical expertise to NYSDOH Clinical Laboratory Evaluation Program (CLEP). The program is responsible for conducting the Clinical Laboratory Improvement Amendments (CLIA)-compliant Proficiency Testing (Mycology) for clinical laboratories in New York State. All analytes for these test events are prepared and standardized internally. The program also provides continuing educational activities in the form of detailed critiques of test events, workshops and occasional one-on-one training of laboratory professionals.

The Journal of Infectious Diseases, 2000

Journal of General Virology, 2012

Human parechoviruses (HPeVs) are picornaviruses frequently infecting humans. While HPeV1 is assoc... more Human parechoviruses (HPeVs) are picornaviruses frequently infecting humans. While HPeV1 is associated with mild disease, HPeV3 is the cause of neonatal sepsis and meningitis. To test whether in vitro replication kinetics of HPeV1 and HPeV3 could be related to pathogenicity, HPeV1 and HPeV3 strains isolated from patients were cultured on cell lines of gastrointestinal, respiratory and neural origin, and replication kinetics were measured by real-time PCR. No relationship was found between clinical symptoms and in vitro replication of the HPeV1 strains. In contrast, the HPeV3 strains showed faster replication in neural cells and there was a relationship between higher in vitro replication kinetics and neuropathogenicity in the patient. Furthermore, HPeV1 could be neutralized efficiently by its specific antibody and by intravenous immunoglobulins (IVIG), while most HPeV3 strains could not be neutralized. In IVIG, very low neutralizing antibody (nAb) titres against HPeV3 were found. Ad...

Journal of Experimental Medicine, 1996

High-density lipoprotein (HDL) has been found to neutralize LPS activity in vitro and in animals ... more High-density lipoprotein (HDL) has been found to neutralize LPS activity in vitro and in animals in vivo. We sought to determine the effects of reconstituted HDL (rHDL) on LPS responsiveness in humans in a double-blind, randomized, placebo-controlled, cross-over study. rHDL, given as a 4-h infusion at 40 mg/kg starting 3.5 h before endotoxin challenge (4 ng/kg), reduced flu-like symptoms during endotoxemia, but did not influence the febrile response. rHDL potently reduced the endotoxin-induced release of TNF, IL-6, and IL-8, while only modestly attenuating the secretion of proinflammatory cytokine inhibitors IL-1ra, soluble TNF receptors and IL-10. In addition, rHDL attenuated LPS-induced changes in leukocyte counts and the enhanced expression of CD11b/CD18 on granulocytes. Importantly, rHDL infusion per se, before LPS administration, was associated with a downregulation of CD14, the main LPS receptor, on monocytes. This effect was biologically relevant, since monocytes isolated fro...

Clinical Infectious Diseases, 2006

Background. Human parechoviruses (HPeVs) are members of the family Picornaviridae and are classif... more Background. Human parechoviruses (HPeVs) are members of the family Picornaviridae and are classified into 3 known serotypes: HPeV1, HPeV2, and the recently identified HPeV3. HPeV1 and HPeV2 infections are most commonly associated with mild respiratory or gastrointestinal symptoms and occasionally with severe disease conditions, such as flaccid paralysis and encephalitis. HPeV3 infection has been associated with transient paralysis and neonatal infection and has until now only been reported in Japan and Canada. Methods. Culture isolates considered to be enterovirus on the basis of cell culture but that were found to be enterovirus negative by 5 untranslated region reverse-transcriptase polymerase chain reaction (5 UTR RT-PCR) during the period December 2000 through January 2005 were selected. Isolates were tested by HPeV 5 UTR RT-PCR and were genotyped by sequencing the VP1 region. Phylogenetic analysis was performed, and the association with clinical symptoms was established. Results. Thirty-seven (12%) of the 303 isolates that tested positive for enterovirus by cell culture were in fact HPeV. The majority of the HPeV-positive isolates () could be identified as HPeV1. The remaining 10 n p 27 isolates, which were grown from samples obtained in 2001, 2002, and 2004, could be typed as the recently identified HPeV3. HPeV was exclusively detected in children aged !3 years. Children infected with HPeV3 were significantly younger than children infected with HPeV1, and sepsis-like illness and central nervous system involvement were more frequently reported in children infected with HPeV3. Conclusions. We report HPeV infections in young children during the period of 2000-2005 and show an association between HPeV3 infection and sepsis-like illness and central nervous system involvement in neonates. Picornaviruses form a group of small, nonenveloped, positive single-stranded RNA viruses that are grouped into 9 genera, including enteroviruses and parechoviruses. The human parechoviruses (HPeVs) were previously known as enteroviruses echo22 and echo23, which were first isolated in 1956 [1, 2]. When molecular techniques were designed for the detection of enterovirus, echo22 and echo23 could not be detected, and sequence analysis revealed that they were genetically distinct from all other picornaviruses. Therefore, they

Clinical and Vaccine Immunology, 2013

ABSTRACTAsymptomaticChlamydia trachomatisinfections are common in HIV-infected men who have sex w... more ABSTRACTAsymptomaticChlamydia trachomatisinfections are common in HIV-infected men who have sex with men (MSM). AlthoughC. trachomatiscombined with HIV would be likely to enhance inflammation, the asymptomatic course suggests otherwise. We assessed local inflammation, mucosal damage, and cytokine concentrations in rectal mucosal fluid samples from patients with HIV (with or without the use of combination antiretroviral therapy [cART]) and with or without the presence of rectalC. trachomatis. Rectal swabs from 79 MSM (with and withoutC. trachomatis, HIV, and cART use) who reported a history of receptive anal sex were analyzed for neutrophil activation (measured by myeloperoxidase [MPO]), mucosal leakage (measured by albumin and alpha-2-macroglobulin), and proinflammatory and anti-inflammatory cytokines.C. trachomatisinfection, HIV infection, and cART use in MSM had no differential effects on rectal neutrophilic inflammation and mucosal damage. Interleukin 8 (IL-8) was found to correl...

Pediatric Infectious Disease Journal, 2021

Supplemental Digital Content is available in the text.

Intensive Care Medicine, May 26, 1997

Blood, Oct 15, 1996

The results of studies with cultured endothelial cells have shown that most von Willebrand factor... more The results of studies with cultured endothelial cells have shown that most von Willebrand factor (vWF) synthesized is directly secreted (constitutive pathway) and consists of both mature vWF, its precursor molecule pro-vWF, and the cleaved vWF prosequence. Only fully processed, functionally mature vWF is stored within the cell, together with the propeptide, and leaves the cell only on stimulation (regulated secretion). Both in resting and stimulated cultured endothelial cells, the stoichiometry of the released propeptide to the released mature vWF is essentially equimolar. In the present study, we have measured the molar ratio of propeptide to mature vWF in vivo, both under resting conditions and conditions that reflect activation of the endothelium. To this end, we devised a method that allows the measurement of the propeptide (vW antigen II) on a quantitative, is, molar basis, using purified recombinant propeptide as a standard. Our results show that the molar concentration of th...

Gastroenterology, 1990

Age-specific changes in glycosylation of rat intestinal lactase-phlorizin hydrolase were analyzed... more Age-specific changes in glycosylation of rat intestinal lactase-phlorizin hydrolase were analyzed using enzyme immunoprecipitated from microvillus membranes of suckling, weaning, and adult rats, and carbohydrate moieties were examined by lectin affinity binding, metabolic labeling, and neuraminidase treatment. Lectin binding indicated the presence of N-linked and O-linked oligosaccharide chains containing mannose and galactose throughout development. An age-dependent shift in sialic acid and fucose was seen during the period of weaning; no fucose was detectable in lactase-phlorizin hydrolase until after the rats were 20 days of age, whereas sialic acid was reduced in adult lactase-phlorizin hydrolase. The presence of sialic acid in suckling intestines and fucose in adult was confirmed by metabolic labeling with appropriate radioactive precursors. Sodium dodecyl phosphate-polyacrylamide gel electrophoresis analysis of immunoprecipitated lactase-phlorizin hydrolase from the proximal a...