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Biomedical subjects

J Jansen

Publications and source records attributed to J Jansen.

At least 55 records · Page 3Linked to original sources

Hematopoietic growth factor after autologous peripheral blood transplantation: comparison of G-CSF and GM-CSF.

Autologous peripheral blood stem cell (PBSC) transplantation results in rapid hematologic recovery when sufficient numbers of CD34+ cells/kg are infused. Recent studies suggest that filgrastim (G-CSF) administration following transplantation leads to more rapid neutrophil recovery and lower total transplant costs. This study compares the use of G-CSF (5 microg/kg/day) with sargramostim (GM-CSF) 500 microg/day from day 0 until neutrophil recovery (ANC >1500/mm3) in patients with breast cancer or myeloma who had PBSC mobilized with the combination of cyclophosphamide, etoposide, and G-CSF. Twenty patients (13 breast cancer and seven myeloma) received GM-CSF and 26 patients (14 breast cancer and 12 myeloma) received G-CSF. The patients were comparable for age and stage of disease, and received stem cell grafts that were not significantly different (CD34+ x 10(6)/kg was 12.5 +/- 11.1 (mean +/- s.d.) for GM-CSF and 19.8 +/- 18.5 for G-CSF; P = 0.10). The use of red cells (2.8 vs 2.3 units), and platelet transfusions (2.5 vs 3.1) was similar for the two groups, as was the use of intravenous antibiotics (4.3 vs 4.6 days) and the number of days with temperature >38.3 degrees C (2.3 vs 1.8). Platelet recovery was also similar in both groups (platelets >50,000/mm3 reached after 11.8 vs 14.9 days). The recovery of neutrophils, however, was faster using G-CSF. ANC >500/mm3 and >1000/mm3 were reached in the GM-CSF group at 10.5 +/- 1.5 and 11.0 +/- 1.7 days, respectively, whereas with G-CSF only 8.8 +/- 1.2 and 8.9 +/- 2.2 days were required (P < 0.001). As a result, patients given G-CSF received fewer injections than the GM-CSF patients (10.9 vs 12.3). Resource utilization immediately attributable to the use of growth factors and the duration of pancytopenia, excluding hospitalization, were similar for the two groups. This study suggests that neutrophil recovery occurs more quickly following autologous PBSC transplant using G-CSF in comparison to GM-CSF, but the difference is not extensive enough to result in lower total cost.

Breast Neoplasms↗

Glucocorticoid receptor ligand binding in monocytic cells using a microplate assay.

Glucocorticoids have profound effects on macrophage function and are widely used as anti-inflammatory drugs. Glucocorticoids receptor (GR) ligand binding capacity is a major determinant of cellular glucocorticoid sensitivity. The number and affinity of GR can be measured in a whole cell binding assay using (3)H-dexamethasone. Here, we describe a rapid and simple microplate assay for GR measurement using the human promonocytic cell line THP-1.

Cell Line↗

Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma.

BACKGROUND: Infections are an important cause of morbidity and mortality in patients with multiple trauma. Studies in both animals and human beings have suggested that glutamine-enriched nutrition decreases the number of infections. METHODS: Patients with multiple trauma with an expected survival of more than 48 h, and who had an Injury Severity Score of 20 or more, were randomly allocated glutamine supplemented enteral nutrition or a balanced, isonitrogenous, isocaloric enteral-feeding regimen along with usual care. Each patient was assessed every 8 h for infection, the primary endpoint. Data were analysed both per protocol, which included enteral feeding for at least 5 days, and by intention to treat. FINDINGS: 72 patients were enrolled and 60 received enteral feeding (29 glutamine-supplemented) for at least 5 days. Five (17%) of 29 patients in the glutamine-supplemented group had pneumonia compared with 14 (45%) of 31 patients in the control group (p<0.02). Bacteraemia occurred in two (7%) patients in glutamine group and 13 (42%) in the control group (p<0.005). One patient in the glutamine group had sepsis compared with eight (26%) patients in the control group (p<0.02). INTERPRETATION: There was a low frequency of pneumonia, sepsis, and bacteraemia in patients with multiple trauma who received glutamine-supplemented enteral nutrition. Larger studies are needed to investigate whether glutamine-supplemented enteral nutrition reduces mortality.

Adult↗

['Public health status and perspectives' 1997. V. Effects of prevention].

For the 'Public health status and forecasts' 1997 attention has been given to the health benefit that could still be achieved by primary and secondary prevention. For selected examples of five types of methods of prevention (health education, vaccination, legislation and regulation, pharmaceutical prophylaxis and screening) the efficacy (the health benefit which can be achieved under optimal circumstances) is compared with the effectiveness (the health benefit achieved in practice). The potential health benefit through interventions aimed at (life-style related) determinants is considerable. It is advised to work towards a programmatic prevention strategy giving attention to ascertaining the correct target group and the most suitable intervention strategy, to regular evaluation of the effectiveness, to implementing an intersectoral approach and to clearly establishing the responsibilities at both the central and the local level.

Forecasting↗

Methyl methanesulfonate-induced hprt mutation spectra in the Chinese hamster cell line CHO9 and its xrcc1-deficient derivative EM-C11.

The Chinese hamster cell mutant EM-C11, which is hypersensitive to the cell killing effects of alkylating agents compared to its parental line CHO9, has been used to study the impact of base excision repair on the mutagenic effects of DNA methylation damage. This cell line has a defect in the xrcc1 gene. XRCC1 can interact with DNA polymerase-beta, thereby suppressing strand displacement, and DNA ligase III, both of which have been implicated in base excision repair. XRCC1 may, therefore, allow efficient ligation of single-strand breaks generated during base excision repair. Both EM-C11 and CHO9 cells were treated with methyl methanesulfonate (MMS), a DNA-methylating agent reacting predominantly with nitrogen atoms generating adducts which are substrates for the base excision repair pathway. EM-C11 cells are much more sensitive to the cytotoxic effects of MMS than CHO9: for EM-C11, the dose of MMS inducing 10% survival is 6-fold lower than that for CHO9. In contrast, mutation induction at the hprt locus following MMS is similar in EM-C11 and CHO9. Molecular analysis of hprt gene mutations showed that although the largest class of hprt mutations, both in EM-C11 and CHO9 cells, consisted of GC > AT transitions, most likely caused by O6-methylguanine, the size of this class was smaller in EM-C11. The fraction of deletion mutants in EM-C11, however, was twice as large as that found in CHO9 cells. These results suggest that reduced ligation efficiency of single-strand breaks generated during base excision repair, as result of a defect in XRCC1, may lead to the formation of deletions.

Animals↗

Fundamental cryobiology of human hematopoietic progenitor cells. I: Osmotic characteristics and volume distribution.

While methods for the cryopreservation of hematopoietic stem cells are well established, new sources of progenitor cells, such as umbilical cord blood, fetal tissue, and ex vivo expanded progenitor cells, may require refined protocols to achieve optimal recovery after freezing. To predict optimal protocols for cryopreservation of human hematopoietic progenitors, knowledge of fundamental cryobiological characteristics including cell osmotic characteristics, water and cryoprotectant permeability coefficients of cell membrane, and activation energies of these coefficients is required. In this study, we used CD34+CD33- cells isolated from human bone marrow as hematopoietic progenitor cell models/representatives to study the osmotic characteristics of the progenitor cells. Volume distribution and osmotic behavior of the CD34+CD33- cells were determined using two different methods: (a) a shape-independent electronic sizing technique and (b) a shape-dependent optical image analysis. The cell diameter was measured to be 8.2 +/- 1.1 microns (mean +/- SD, n = 1,091,475, the number of donors = 8) using the electronic sizing technique or 8.7 +/- 1.2 microns (mean +/- SD, n = 1508, the number of donors = 6) by image analysis at initial (isotonic) osmolality, 325 mosm/kg. The cell volume change was measured after the cells were exposed and equilibrated to different anisosmotic conditions. The cell volume was found to be a linear function of the reciprocal of the extracellular osmolality (Boyle van't Hoff plot) ranging from 163 to 1505 mosm/kg. The volume fraction of intracellular water which is osmotically active was determined to be 79.5% of the cell volume. It was concluded that human CD34+CD33- cells osmotically behave as ideal osmometers. This information coupled with cell water and cryoprotectant permeability coefficients as well as their activation energies (to be determined in the ongoing research projects) will be used to design optimum conditions for cryopreservation of human hematopoietic progenitor cells.

Antigens, CD↗

Hangman's fracture: arguments in favor of surgical therapy for type II and III according to Edwards and Levine.

BACKGROUND: The optimal therapy for traumatic fractures of the neural arch of the axis, the so-called hangman's fractures, is still controversial. Indications for surgery depend on the type of hangman's fracture and/or additional injuries of the intervertebral disc or ligaments. METHODS: Sixteen patients sustaining fractures of the neural arch of the axis were treated by the screw fixation technique evolved by Judet. The passive mobility of the cervical spine was analyzed postoperatively by the radiographic evaluation method of Dvorak and coworkers and Penning. The angulation and anterior translation of C2 on C3 was measured before and after surgery. RESULTS: Follow-up investigations 3, 12, and in some cases 45 months later confirmed sufficient functional results especially regarding the mobility of the upper cervical spine. Comparison of pre- and postoperative angulation and anterior translation of C2 on C3 revealed a significant improvement especially in cases with type IIa fractures. CONCLUSION: The stabilization technique of Judet facilitates an exact reconstruction of anatomical conditions thereby preserving the atlantoaxial rotational mobility. A negligible hypomobility of the C2-C3 segment was observed on average 18 months after surgery.

Adult↗

Immunological properties of recombinant proteins of the transmission blocking vaccine candidate, Pfs48/45, of the human malaria parasite Plasmodium falciparum produced in Escherichia coli.

A precondition for the development of a transmission blocking vaccine based on the sexual stage-specific surface antigen Pfs48/45 of Plasmodium falciparum is its heterologous synthesis in a native state. Here we describe the production of recombinant Pfs48/45 in Escherichia coli. Two recombinant proteins, of which one is a glutathione-S-transferase fusion protein, were produced. Enzyme-linked immunosorbent assays showed that at least a subfraction of the recombinant proteins had a conformation capable of binding transmission blocking monoclonal antibodies. However, despite the fact that both proteins were very immunogenic, they did not induce transmission blocking immunity in mice or rabbits. Immunological studies with congenic mouse strains demonstrated that immune responses could be boosted with gametocyte extracts and were not restricted to a particular class II major histocompatibility complex haplotype.

Animals↗

Glycerol gangliotomy of the second dorsal cervical root in rats: an experimental study to evaluate a minimal invasive approach for the treatment of the chronic cervicogenic headache.

Glycerol is a known agent in the therapy of chronic tic douloureux. It has been used for about 20 years in percutaneous, retrogasserian minimal-invasive rhizotomy, although the pharmacological mechanism of the pain relief involved remains unclear. To investigate glycerol treatment as a possible replacement for invasive approaches in the therapy of chronic cervicogenic headaches, we performed an experimental study on the pathomorphologic action of anhydrous glycerol injection into the second upper cervical dorsal root ganglion (DRG) of rats. Glycerol injections into the second cervical ganglion were investigated light- and electron-microscopically in a series of 40 rats for survival times of up to 30 days. We detected an unspecific overall effect on sensory neurons and satellite cells, as well as on myelinated and unmyelinated axons and Schwann cells. This could be detected after 5 days and sometimes led to degeneration of most of the neurons. Contralateral saline injections as a control showed no morphological effects. The loss of afferent fiber connections to the posterior horn of the myelon could be detected by immunohistochemical labeling of reactive astrocytes. Our results show a glycerol-induced deterioration of the cytoarchitecture of the neurons and their glial satellite cells. The effects on the ganglion cells appear to have been mediated by membrane disturbances and loss of glial integrity. These observations are contrary to previously reported results indicating the specific effect of glycerol on thin myelinated sensory axons.

Animals↗

The incidence of suspected myocardial infarction in Dutch general practice in the period 1978-1994.

AIM: To evaluate how the incidence of suspected myocardial infarction has developed from 1978 to 1994 and to study the incidence of confirmed acute myocardial infarction in Dutch general practices during the period 1991-1994. METHODS: In three periods (1978, 1983-1985 and 1991-1994) the incidence of suspected myocardial infarction has been registered by the 'Dutch Sentinel Practice Network'. This is a registration system that obtains data from general practitioners covering about 150,000 persons. During the period 1991-1994 the incidence of confirmed myocardial infarction was also registered. RESULTS: For men, the incidence rate of suspected myocardial infarction decreased by 28% from 4.7 per 1000 in 1978 to 3.4 per 1000 in the period 1991-1994. For women, the incidence fell by 23% from 2.6 per 1000 in 1978 to 2.0 per 1000 in the period 1983-1985 and stabilized thereafter. The most pronounced decrease in the incidence of suspected myocardial infarction during the period 1978-1994 occurred in both men and women aged 45-64. In the period 1991-1994, the standardized incidence rate of confirmed myocardial infarction is 1.7 per 1000 for men and 0.9 per 1000 for women. CONCLUSIONS: These data suggest that the incidence of suspected myocardial infarction has declined substantially between 1978 and 1994 both for men and for women; this decline is most pronounced in the age group 45-64.

Adult↗

Modulation of cytokine release and neutrophil function by granulocyte colony-stimulating factor during endotoxemia in humans.

In this double-blind, cross-over, placebo-controlled, randomized study, two groups of eight healthy male volunteers were challenged with endotoxin (4 ng/kg) on two occasions, once in conjunction with placebo and once with granulocyte colony-stimulating factor (G-CSF; 5 microg/kg). In group 1, G-CSF was administered intravenously 2 hours before endotoxin challenge; in group 2, G-CSF was administered subcutaneously 24 hours before endotoxin challenge. In group 1, G-CSF significantly enhanced the release of tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-8, IL-1 receptor antagonist (IL-1ra), and soluble TNF receptors. In group 2, G-CSF significantly reduced IL-8 concentrations and modestly attenuated TNF and IL-6 levels. In this group, IL-1ra and soluble TNF receptors were enhanced by G-CSF pretreatment and lipopolysaccharide (LPS)-induced soluble TNF receptor release was further augmented, whereas LPS-induced IL-1ra concentrations remained unaltered. Both pretreatments with G-CSF increased LPS-induced peripheral neutrophilia; the expression of CD11b, CD18, and CD67; and the release of elastase and lactoferrin. Both pretreatments also down-regulated neutrophil L-selectin expression and prevented the endotoxin-induced pulmonary neutrophil accumulation during the first 2 hours after endotoxin challenge. These data indicate that two different pretreatments with G-CSF result in differential effects on LPS-induced cytokine release but similar effects on LPS-induced neutrophil activation and changes in expression of cell surface molecules. Finally, regardless of the effects of G-CSF on LPS-induced cytokine release, G-CSF blocks LPS-induced pulmonary granulocyte accumulation.

Cell Degranulation↗

Prediction of success from a multidisciplinary treatment program for chronic low back pain.

STUDY DESIGN: The study included 90 disabled patients with chronic low back pain recruited from a pain clinic who were admitted to an 8-week program of functional restoration and behavioral support. Initial evaluations included a medical examination, rating of the physical impairment, a personal interview, a visual analogue scale to record pain intensity, an assessment of limitations for daily activities, a pain disability index, a depression and psychovegetative scale, and a scale to evaluate general living standards. The physical assessment included different flexibility measurements, measurement of power and endurance through standardized exercises, and measurements of isokinetic trunk and lifting strength and general endurance. The measurements were repeated at the end of the 8-week program and thereafter an intervals of 6 and 12 months. Final analyses were carried out on 82 patients. OBJECTIVES: To determine whether objective or subjective signs most influence the outcome of rehabilitation. SUMMARY OF BACKGROUND DATA: In recent years, several studies have shown that active and intensive multimodal treatment of chronic low back pain is successful. Until now there has been lack of information about which patients will respond to the therapy and what is the most effective part of treatment. METHODS: Prognostic factors (return to work, pain intensity, self-assessment of treatment success by patients) were tested by studying variance and regression analyses for their ability to predict treatment outcome. RESULTS: Certain factors were identified that had a significant impact on determining the probability of a patient's return to work and the reduction of pain intensity. These factors included self-evaluation for predicting a return to work, the length of absence from work, application for pension, and a decrease is disability after treatment. Overall satisfaction with treatment was best determined by the number of medical consultations before treatment, the extent of disability, previous measures taken for coping with the disease, and reduction of disability during treatment. Medical background, medical diagnosis, and physical impairment had no predictive value. Physical variables (i.e., mobility, strength, endurance, and physical performance) also demonstrated only limited predictive value. CONCLUSION: This study has demonstrated that the most important variable in determining a successful treatment of chronic low back pain is the reduction of subjective feelings of disability in patients.

Adult↗

Database on the structure of small ribosomal subunit RNA.

The Antwerp database on small ribosomal subunit RNA now offers more than 6000 nucleotide sequences (August 1996). All these sequences are stored in the form of an alignment based on the adopted secondary structure model, which is corroborated by the observation of compensating substitutions in the alignment. Besides the primary and secondary structure information, literature references, accession numbers and detailed taxonomic information are also compiled. For ease of use, the complete database is made available to the scientific community via World Wide Web at URL http://rrna.uia.ac.be/ssu/ .

Animals↗

Progression of arteriovenous malformation in moyamoya syndrome.

We report a case of moyamoya disease (MMD) associated with arteriovenous malformation (AVM). The 30-year-old female patient presented with left-hemispheric transient ischaemic attacks (TIAs) involving dysphasia and right-sided hemiparesis. CT-scan and lumbar puncture showed no evidence of intracranial haemorrhage. Cerebral angiography revealed typical moyamoya vessels and occlusion of multiple cerebral arteries with consecutive collateral blood supply. Moreover, a left-parietal AVM with a diameter of approximately 2 cm was detected. An extra-intracranial arterial bypass (EIAB) connecting the left superficial temporal artery (STA) with a cortical branch of the left middle cerebral artery (MCA) was performed (STA-MCA anastomosis) and yielded subsequent resolution of the neurological deficit. Nine months post-operatively neurological deficits similar to those of the initial presentation recurred. Repeated angiography suggested comparatively increased AVM blood flow, and successful extirpation of the AVM gradually re-established almost full functional ability. However, deterioration of the neurological condition developed again. We herewith present the first European case of moyamoya disease associated with arteriovenous malformation and report the clinical course under an alternative neurosurgical treatment consisting of STA-MCA anastomosis and delayed extirpation of the AVM.

Adult↗

[Frequent problems with antibiotic chemotherapy of bacterial CNS diseases. Case reports and recommendations for initial treatment].

The initial antibiotic treatment of bacterial meningoencephalitis has major implications for the course of the disease. The current spectrum of infectious agents must be considered. Antibiotics have to reach sufficient concentrations in the blood and cerebrospinal fluid for a bactericidal action to occur at the site of infection. Frequent problems arising in this condition are: (1) the non-observation of listerial infections, (2) the use of antibiotics not sufficiently active against gram-positive bacteria in pneumococcal meningitis, (3) the development of meningitis following the use of ciprofloxacin in respiratory tract infections, (4) the hasty change in antibiotic regimens in focal parenchymal infections during delayed response to therapy, (5) the use of bacteriostatic antibiotics, and (6) the delay in administering sufficient antibiotic therapy during fulminate meningococcal meningitis. Problems arising from these conditions are illustrated by case reports.

Adolescent↗

Counterflow centrifugal elutriation as a method of T cell depletion may cause loss of immature CD34+ cells.

Counterflow centrifugal elutriation (CCE) is capable of separating cells on the basis of size. CCE has been used successfully to deplete allogeneic bone marrow (BM) grafts of T lymphocytes to decrease the risk of acute graft-versus-host disease. Previous studies have shown that more immature CD34+ cells in human BM tend to be smaller than more mature CD34+ cells. Human BM was subjected to CCE with the 4 ml standard chamber at constant rotor speed (2300 r.p.m.) and increasing flow-rate (14-23 ml/min, rotor-off). The eleven fractions collected were assayed for CD34+ and CD3+ cells, and for CFU-GM, HPP-CFC and long-term culture initiating cells (LTC-IC). The CD3+ T cells were enriched in the early (small-cell) fractions 14-17 ml/min. CD34+ cells were enriched in fractions 17-21 ml/min, and CFU-GM were concentrated in the same fractions. HPP-CFC and LTC-IC showed nearly identical CCE profiles, with enrichment in fractions 16-18 ml/min. When fraction < or = 17 ml/min was chosen as cut-off, the small-cell fraction contained 94.0% of all CD3+ cells, 44.4% of total cells, 33.2% of CD34+ cells and 34.7% of CFU-GM; however, 67.6% of HPP-CFC and 72.4% of LTC-IC were recovered in this small-cell fraction. These data suggest that T cell depletion through CCE as used by us, while losing only minor proportions of CD34+ cells and CFU-GM, carries the risk of losing the majority of more immature progenitor cells. This may lead to an increased risk of graft failure, in particular in HLA-mismatched transplants.

Antigens, CD34↗

In contrast to their murine counterparts, normal human keratinocytes and human epidermoid cell lines A431 and HaCaT fail to express IL-10 mRNA and protein.

In mice, keratinocyte-derived IL-10 is up-regulated by ultraviolet-B (UVB) radiation and plays a major role in UVB-induced immunosuppression. The present study was designed to examine whether a comparable phenomenon can be detected in man. Freshly isolated or cultured normal human keratinocytes (NHK) and keratinocyte cell lines A431 and HaCaT were stimulated with graded doses of UVB (up to 200 J/m2) or with a variety of other stimuli. RNA was extracted at various time points post-stimulation and analysed by reverse transcriptase-polymerase chain reaction (RT-PCR) using four different IL-10-specific primer pairs and RNA from monocytes or T cells as positive controls. We failed to detect IL-10 mRNA in NHK from 40 different donors (breast, abdomen, leg, scalp, foreskin) and in A431 and HaCaT cells, irrespective of the stimulation used and despite successful stimulation. Supernatants of NHK, A431 and HaCaT cultures were negative for IL-10 protein, as tested by four different ELISAs and a bioassay. Murine keratinocytes, stimulated under comparable conditions and tested by the same techniques, displayed a strong expression of IL-10 mRNA and protein. Remarkably, an IL-10 mRNA signal could be detected in NHK after a second round of PCR amplification. Because NHK suspensions are contaminated with Langerhans cells, melanocytes and possibly fibroblasts, we tested pure populations of each individual cell type to determine the origin of this IL-10 mRNA. Our results clearly indicate that NHK, Langerhans cells and fibroblasts fail to express IL-10 and that melanocytes are the principal source of IL-10 mRNA in normal human epidermis.

Animals↗