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Biomedical subjects

A Visser

Publications and source records attributed to A Visser.

At least 37 records · Page 2Linked to original sources
PubMed2001

Subunits of the translation initiation factor eIF2B are mutant in leukoencephalopathy with vanishing white matter.

Leukoencephalopathy with vanishing white matter (VWM) is an inherited brain disease that occurs mainly in children. The course is chronic-progressive with additional episodes of rapid deterioration following febrile infection or minor head trauma. We have identified mutations in EIF2B5 and EIF2B2, encoding the epsilon- and beta-subunits of the translation initiation factor eIF2B and located on chromosomes 3q27 and 14q24, respectively, as causing VWM. We found 16 different mutations in EIF2B5 in 29 patients from 23 families. We also found two distantly related individuals who were homozygous with respect to a missense mutation in EIF2B2, affecting a conserved amino acid. Three other patients also had mutations in EIF2B2. As eIF2B has an essential role in the regulation of translation under different conditions, including stress, this may explain the rapid deterioration of people with VWM under stress. Mutant translation initiation factors have not previously been implicated in disease.

Base Sequence↗
PubMed2000

Most marginal zone B cells in rat express germline encoded Ig VH genes and are ligand selected.

The present study was performed to analyze whether marginal zone B (MZ-B) cells in nondeliberately immunized adult rats are selected on basis of the specificity of their B cell receptor, and to determine to what extent memory B cells contribute to the MZ-B cell subset. To this end, the Ig PC7183 V(H) gene repertoire was studied among V(H)DJ(H)-mu transcripts expressed in four sequential stages of B cell development, of two individual untreated adult rats. B cell subsets, i.e., pro/pre-B cells and newly formed B (NF-B) cells from bone marrow, and recirculating follicular B cells and MZ-B cells from spleen were sorted by flow cytometry. In addition, from one these rats, cells were microdissected from follicular and MZ areas of the spleen and productive PC7183 V(H) gene rearrangements were analyzed for the presence of somatic mutations. Sequence analysis reveals that most MZ-B cells in the adult rat, either defined by flow cytometry or by their anatomical location in the spleen, express germline encoded V(H) genes (naive MZ-B cells) and a minor fraction (about 20%) of the MZ-B cells carry somatic mutations (memory MZ-B cells). In addition, we show that naive MZ-B cells are a selected population of cells, both based on PC7183 V(H) gene repertoire and on the length of the Ig heavy (H) chain complementarity-determining region 3 (H-CDR3) region, i.e., PC7183 V(H)DJ(H)-mu transcripts of MZ-B cells carry significantly shorter H-CDR3 regions than other B cell subsets.

Amino Acid Sequence↗
PubMed2000

EST sequencing of the parasitic nematode Haemonchus contortus suggests a shift in gene expression during transition to the parasitic stages.

Expressed sequence tags from the parasitic nematode Haemonchus contortus were generated in order to identify anchor loci for comparative mapping between nematode genomes and candidate targets for future control measures. In total, 370 SL1 trans-spliced cDNAs from different developmental stages representing 195 different genes were partially sequenced. From these expressed sequence tags 50% were similar to genes with a known or predicted function and 19% were similar to nematode sequences with no ascribed function. From the first, free-living L1 and L3 stages relatively many cDNAs matched to housekeeping genes, and 11% (L1) or 23% (L3) of the encoded proteins were predicted to contain signal peptides. In contrast, no function could be ascribed to most of the cDNAs from the early L5 and adult parasitic stages, but for 30% (L5) or 55% (adult) of the encoded proteins a signal sequence was predicted. This limited analysis suggests that during the transition from the free-living to parasitic stages gene expression shifts towards the synthesis of less conserved extracellular proteins. These proteins offer the best perspectives for vaccine development and the development of anthelmintic drugs. In contrast, cDNAs from the first larval stages may be most suitable for comparative mapping with the free-living nematode Caenorhabditis elegans.

Animals↗
PubMed2000

Caring for caregivers: experiences and evaluation of interventions for a palliative care team.

Palliative care is a fairly recent development in The Netherlands. The first palliative unit in a hospital setting was the Palliative Care Unit (PCU) in the Dr Daniel den Hoed Clinic, a specialized oncology hospital, now part of the Academic Hospital Rotterdam (AZR-Daniel). This PCU was designed to function as an academic laboratory, where palliative care concepts are being developed, put into practice, and evaluated. It's mission was to put the patient first in mind, heart and soul. Right from the start, special attention was paid to the implementation a system of 'care for caregivers' in order to support the staff of the PCU in caring for the terminally ill and to prevent burnout. A process evaluation has been carried out with a special focus on the effects of the implementation of the new unit on the wellbeing of the interdisciplinary team of caregivers during the first year of its existence and on the experiences with a residential training preceding the start of patient care activities and the weekly staff support meetings. In the second half of the first year, the PCU staff experienced increased levels of job-related stress. Most stress was attributed to organizational factors, related to management issues but also to lack of institutional support. Teamwork also contributed to stress within the interdisciplinary team. Direct patient care activities also had some impact on experienced stress levels, through a heavy work-load of complex care, a shortage of staff and an experienced lack of competence. While the staff support activities were designed to give emotional support and deal with death and bereavement, these issues did not arise as major problems. As a consequence, the staff support in the PCU was perhaps less successful than it could have been. However, the high stress levels of this innovative palliative team warrant attention. We discuss how support meetings could be a more effective way of caring for staff. They should be accompanied by adequate resources, a supportive management structure, and an extensive educational program.

Adult↗
PubMed2000

Issues in Dutch palliative care: readjusting a distorted image.

This issue presents a review of several issues in Dutch palliative care, paying attention to readjusting a distorted image due to the euthanasia practice in the Netherlands. A few articles stress the evolution of palliative care (especially in the UK and the Netherlands), developed palliative care services in the Netherlands, and new developments in the Netherlands concerning the prevention of euthanasia through palliative care. Also the needs concerning palliative care for children as well as for chronic psycho-geriatrics patients are presented. Further attention is paid to the organisation of palliative care, focusing at evaluative research on palliative support teams, caring for caregivers (experiences and evaluation of interventions for palliative care teams), and effects of transmural care on coordination and continuity of care. Finally, some articles focus on ethical considerations in the treatment of pain in hospice movement, ethical evaluation of clinical trials in palliative care, and the role of informed consent in palliative radiotherapy, stressing the participation of patients and proxies in treatment decisions. Conclusions are presented on the consequences for educational and counselling aspects of palliative care.

Ethics, Medical↗
PubMed2000

A controlled clinical trial of implant-retained mandibular overdentures; five-years' results of clinical aspects and aftercare of IMZ implants and Brånemark implants.

The aim of this prospective randomized controlled clinical trial was to evaluate a set of clinical items and prosthetic aftercare of edentulous patients with a mandibular overdenture retained by 2 IMZ implants or 2 Brånemark implants during a 5-years' period. Patients were allocated to the IMZ group (n = 29) or the Brånemark group (n = 32) by a computerized balancing method. In the IMZ group 4 implants were lost during the 5-years' follow-up (survival rate: 93%). In the Brånemark group 9 implants were lost (survival rate: 86%). All patients were re-operated successfully. Multiple prosthetic revisions were necessary in both groups, especially the precision attachment system in the overdenture was subject to frequent fracture or loosening. From this study can be concluded that there is no difference in clinical state, radiographical state, survival rate and clinical implant performance between the IMZ implant system and the Brånemark implant system supporting an overdenture on 2 implants after 5 years of follow-up.

Chi-Square Distribution↗
PubMed1999

Organization of early and late replicating DNA in human chromosome territories.

It has been suggested that DNA organized into replication foci during S-phase remains stably aggregated in non-S-phase cells and that these stable aggregates provide fundamental units of nuclear or chromosome architecture [C. Meng and R. Berezney (1991) J. Cell Biol. 115, 95a; E. Sparvoli et al. (1994) J. Cell Sci. 107, 3097-3103; D. A. Jackson and A. Pombo (1998) J. Cell Biol. 140, 1285-1295; D. Zink et al. (1998) Hum. Genet. 112, 241-251]. To test this hypothesis, early and late replicating DNA of human diploid fibroblasts was labeled specifically by incorporating two different thymidine analogs [J. Aten (1992) Histochem. J. 24, 251-259; A. E. Visser (1998) Exp. Cell Res. 243, 398-407], during distinct time segments of S-phase. On mitotic chromosomes the amount and spatial distribution of early and late replicating DNA corresponded to R/G-banding patterns. After labeling cells were grown for several cell cycles. During this growth period individual replication labeled chromosomes were distributed into an environment of unlabeled chromosomes. The nuclear territories of chromosomes 13 and 15 were identified by additional chromosome painting. The distribution of early and late replicating DNA was analyzed for both chromosomes in quiescent (G0) cells or at G1. Early and late replicating DNA occupied distinct foci within chromosome territories, displaying a median overlap of only 5-10%. There was no difference in this regard between G1 and G0 cells. Chromosome 13 and 15 territories displayed a similar structural rearrangement in G1 cells compared to G0 cells resulting in the compaction of the territories. The findings demonstrate that early and late replicating foci are maintained during subsequent cell cycles as distinctly separated units of chromosome organization. These findings are compatible with the hypothesis that DNA organized into replicon clusters remains stably aggregated in non-S-phase cells.

Cells, Cultured↗
PubMed1999

Changes in transforming growth factor-beta (TGF-beta 1), procollagen types I and II mRNA in the rat heart after irradiation.

PURPOSE: To study alteration in gene transcription (transforming growth factor-beta 1 and procollagen types I and III) involved in radiation-induced cardiac damage. MATERIALS AND METHODS: Female Sprague-Dawley rats were irradiated with a single dose of 0, 15, 20 or 25 Gy locally on the heart. At intervals up to 16 months after irradiation, absolute amounts of mRNA were quantified using a (semi-nested) competitive PCR assay. All values were normalized to equal input cDNA with respect to their GAPDH content. RESULTS: After irradiation, left ventricular TGF-beta 1 mRNA levels increased sharply. This response was bi-phasic with peaks at days 1 and 12 (maximum 6-fold baseline), then returning to control levels by 1 month. After 20 Gy, a persistent elevation was observed from 6 months, but this elevation was less profound (approximately 1.5-fold baseline) when compared with the early response (1-12 days). Absolute mRNA levels of procollagen type I hardly changed during the first 6 months, but thereafter these levels increased progressively until the end of observation. An age-related increase in procollagen I was also observed. Procollagen type III mRNA levels were increased between days 1 and 12, returned to control values and remained low up to 6 months, then mRNA levels rose again with increasing time post-treatment. CONCLUSION: The difference in time-course between TGF-beta 1 and procollagen mRNA expression after local heart irradiation and ageing strongly suggest that the late up-regulation of both procollagen types in the left ventricle occurs without TGF-beta 1 over-expression.

Animals↗
PubMed1998

Long-term competition between sulfate reducing and methanogenic bacteria in UASB reactors treating volatile fatty acids.

The competition between acetate utilizing methane-producing bacteria (MB) and sulfate-reducing bacteria (SRB) was studied in mesophilic (30 degrees C) upflow anaerobic sludge bed (UASB) reactors (upward velocity 1 m h-1; pH 8) treating volatile fatty acids and sulfate. The UASB reactors treated a VFA mixture (with an acetate:propionate:butyrate ratio of 5:3:2 on COD basis) or acetate as the sole substrate at different COD:sulfate ratios. The outcome of the competition was evaluated in terms of conversion rates and specific methanogenic and sulfidogenic activities. The COD:sulfate ratio was a key factor in the partitioning of acetate utilization between MB and SRB. In excess of sulfate (COD:sulfate ratio lower than 0.67), SRB became predominant over MB after prolonged reactor operation: 250 and 400 days were required to increase the amount of acetate used by SRB from 50 to 90% in the reactor treating, respectively, the VFA mixture or acetate as the sole substrate. The competition for acetate was further studied by dynamic simulations using a mathematical model based on the Monod kinetic parameters of acetate utilizing SRB and MB. The simulations confirmed the long term nature of the competition between these acetotrophs. A high reactor pH (+/-8), a short solid retention time (<150 days), and the presence of a substantial SRB population in the inoculum may considerably reduce the time required for acetate-utilising SRB to outcompete MB.

Acetates↗
PubMed1998

Effect of mild acute stress on immune cell distribution and natural killer cell activity in breast cancer patients.

The present study explored cardiovascular and immune responses to a standardized laboratory challenge (speech task) in 23 breast cancer patients. All patients were diagnosed with positive axilliary lymph nodes and received tamoxifen as an adjuvant treatment throughout the course of the study. As a control group, 15 age-matched healthy women were included. At baseline, there were no differences in blood pressure and heart rate values between breast cancer patients and healthy women. With respect to the lymphocyte subsets at baseline, patients had significantly higher absolute numbers of CD16/56 (NK) cells. We speculate that the increase in circulating NK cells can be either a sign of activation of aspecific natural immunity caused by tumor cells or an immunostimulatory effect of tamoxifen. No differences were found in total lymphocyte count and numbers of CD3, CD4, CD8 or CD19 (B) cells. The pattern of changes induced by the speech task with regard to number and function of peripheral immune cells confirm earlier findings derived from healthy subjects. Overall, marked increases were observed in NK and CD8 cells, whereas smaller changes were observed in number of CD4 and CD19 (B) cells in response to the speech task. There were no significant differences in the acute stress-induced immune cell changes between breast cancer patients and healthy women. These results seem to implicate that the distribution of immune cells is intact in patients with localized breast disease. With respect to natural killer cell activity (NKCA), our results, as do those of others, show a significant increase in response to the speech task in both healthy women and patients. Compared to the NKCA responses of healthy women, those of breast cancer patients appeared to be delayed. Potential mechanisms behind this difference are discussed.

Aged↗