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Biomedical subjects

A Smits

Publications and source records attributed to A Smits.

53 records · Page 3Linked to original sources
PubMed1992

Expression of platelet-derived growth factor and its receptors in proliferative disorders of fibroblastic origin.

Platelet-derived growth factor (PDGF) is known to stimulate the proliferation of connective tissue-derived cells in vitro. Less is known about its functions in vivo, and the role of PDGF in the development of human tumors has not been clarified. The authors have investigated the occurrence of PDGF and PDGF receptors in a series of proliferative disorders of fibroblastic origin using immunohistochemical and in situ hybridization techniques. High expression of PDGF beta-receptor mRNA and protein was found in the malignant tumors, and also in some benign lesions, such as dermatofibroma. In all these cases, benign as well as malignant, the PDGF B-chain mRNA, and less clearly, the PDGF A-chain mRNA, were coexpressed with the beta-receptor. In contrast, high expression of PDGF alpha-receptor mRNA was only found in fully malignant lesions, i.e., malignant fibrous histiocytoma. These data indicate that an autocrine growth stimulation via the PDGF beta-receptor could occur in an early phase of tumorigenesis, and may be a necessary but insufficient event for the progression into fully malignant human connective tissue lesions.

Alcian Blue↗
PubMed1991

Neurotrophic activity of platelet-derived growth factor (PDGF): Rat neuronal cells possess functional PDGF beta-type receptors and respond to PDGF.

The different isoforms of PDGF bind with different affinities to two different receptor types. Previously, these receptors have been demonstrated mainly on mesenchymal and glial cells. We show here that PDGF beta-type receptors are present also on rat brain neurons in vivo as well as in vitro. Immunohistochemical analysis of a sequentially sectioned brain of a newborn rat revealed the presence of PDGF beta receptors in neurons throughout the central nervous system. These beta-receptor-bearing cells were shown to contain neurofilaments by double immunofluorescence staining. Furthermore, the PDGF-BB isoform bound to cells in a neuron-enriched culture from newborn rat brains and induced c-Fos protein in these cells. Continuous PDGF-BB treatment of primary rat brain cell cultures resulted in outgrowth of neurites and prolonged survival. These results indicate a neurotrophic effect of PDGF-BB.

Animals↗
PubMed1991

New distal marker closely linked to the fragile X locus.

We have isolated II-10, a new X-chromosomal probe that identifies a highly informative two-allele TaqI restriction fragment length polymorphism at locus DXS466. Using somatic cell hybrids containing distinct portions of the long arm of the X chromosome, we could localize DXS466 between DXS296 and DXS304, both of which are closely linked distal markers for fragile X. This regional localization was supported by the analysis, in fragile X families, of recombination events between these three loci, the fragile X locus and locus DXS52, the latter being located at a more distal position. DXS466 is closely linked to the fragile X locus with a peak lod score of 7.79 at a recombination fraction of 0.02. Heterozygosity of DXS466 is approximately 50%. Its close proximity and relatively high informativity make DXS466 a valuable new diagnostic DNA marker for fragile X.

Animals↗
PubMed1991

Community HIV/AIDS teams.

This paper describes a consecutive series of 103 patients with HIV and AIDS related illnesses who were referred to, and remained in, the care of two community teams. The characteristics of the patients are outlined and the early experiences of the teams are described. The findings of this study should assist doctors and nurses caring for patients with HIV and AIDS related illnesses in the community, and provide valuable data for service planners.

Acquired Immunodeficiency Syndrome↗
PubMed1990

A novel function of the transforming domain of E1a: repression of AP-1 activity.

Adenovirus E1a represses transcription of the collagenase gene via the phorbol ester-responsive element (collTRE). The mechanism involves inhibition of the trans-activating function of the transcription factor AP-1 without reduction of its synthesis and without any apparent change in DNA binding or composition. The ability of E1a to downmodulate AP-1 is a unique property among dominant oncogenes. This repression depends on conserved region 1, one of the transforming domains of E1a, indicating that it is an integral feature of adenovirus transformation.

Adenovirus Early Proteins↗
PubMed1990

Facilitating care of patients with HIV infection by hospital and primary care teams.

To complement the role of primary care teams working with patients with HIV disease and AIDS within greater London and to ease the load on the special hospital units a home support team was developed. It comprises six specialist nurses, a general practitioner trained medical officer, and a receptionist and is funded from regional and district sources and charities. A nurse is available for out of hours and emergency weekend calls, with support from the patient's general practitioner or the attached medical officer. During the first 18 months 249 patients were seen; the mean duration of care was five months. Nearly a third (18/50, 30%) of patients who were terminally ill died at home. The team's activities included practical nursing care, emotional support for carers and patients, and advice and guidance to primary care teams. Problems in providing care in patients' homes included issues relating to confidentiality and 24 hour cover. With the increasing incidence of HIV infection the home support team may be a useful model for care of large numbers of patients with symptomatic HIV disease, especially in large urban areas.

Acquired Immunodeficiency Syndrome↗
PubMed1990

New polymorphic DNA marker close to the fragile site FRAXA.

DNA from a human-hamster hybrid cell line, 908-K1B17, containing a small terminal portion of the long arm of the human X chromosome as well as the pericentric region of 19q was used as starting material for the isolation of an X-chromosome-specific DNA segment, RN1 (DXS369), which identifies a XmnI RFLP. Linkage analysis in fragile X families resulted in a maximum lod score of 15.3 at a recombination fraction of 0.05 between RN1 and fra(X). Analysis of recombinations around the fra(X) and distal to DXS105. Analysis of the marker content of hybrid cell line 908K1B17 suggests the localization of RN1 between DXS98 and fra(X). Heterozygosity of DXS369 is approximately 50%, which extends the diagnostic potential of RFLP analysis in fragile X families significantly.

Animals↗
PubMed1989

Rat brain capillary endothelial cells express functional PDGF B-type receptors.

Immunohistochemical staining revealed the presence of platelet-derived growth factor (PDGF) B-type receptors on capillaries of normal rat brain. Furthermore, capillary endothelial cells isolated from rat brain and grown in tissue culture bound [125I]PDGF-BB but not [125I]PDGF-AA, suggesting that they expressed B-type, but not A-type, PDGF receptors. PDGF-BB and PDGF-AB, but not PDGF-AA, also stimulated incorporation of [3H]thymidine into these cells. Thus, rat brain capillary endothelial cells have functional B-type receptors, and thereby differ from endothelial cells derived from large blood vessels, that do not express PDGF receptors. Our data suggest a possible role for PDGF-BB as an angiogenic factor.

Angiogenesis Inducing Agents↗
PubMed1988

Effect of bereavement on the health of the remaining family members.

This investigation focuses on the effect of the death of a family member on the number and type of diagnosed illnesses of the remaining members. The data on mortality and morbidity were obtained from a continuous morbidity register. A total of 225 cases of death were selected, involving 313 family members. A control group of 4909 people who had not been confronted with a death of a family member were selected. A comparison of morbidity rates for the two groups showed that morbidity rates, both for minor and serious illnesses, were affected by the death of a family member. Increases in minor illnesses occurred more often when people had been confronted with death after a chronic illness; increases in serious illnesses were mainly found among people confronted with sudden death. Surprisingly, people with nervous disorders in their medical history showed fewer diagnoses for minor illnesses after a sudden death of a family member. An explanation may be found in the basic principles of family medicine.

Attitude to Death↗
PubMed1985

Work satisfaction of general practitioners and the quality of patient care.

The emotional reactions of 57 general practitioners to three aspects of work was assessed by means of questionnaires. The quality of patient care was assessed by means of observations of general practice consultations, assessment of audiotaped consulting hour contacts and an analysis of the referral and prescription figures. A distinction was made between the degree of positive and the degree of negative feelings general practitioners have about their work. Many positive feelings (satisfaction, feeling at ease) correlated with more openness to patients, more attention to psychosocial aspects of the complaints but also with a higher rate of referral to medical specialists. On the other hand, many negative feelings (frustration, tension, lack of time) correlated with a high prescription rate and with giving little explanation to patients. To some extent the way that work is experienced by general practitioners correlated with the quality of care for the patients, but what constitutes cause and effect requires further study. A reflection of a doctor's own feelings about work should become part of training, continuing education and medical audit programmes.

Drug Prescriptions↗
PubMedDate not supplied

Multipoint linkage analysis of DXS369 and DXS304 in fragile X families.

Diagnosis of carriers of the fragile-X mental retardation gene is hampered by the paucity of tightly linked DNA markers. Recently, 2 new DNA markers RN1 (DXS369) and U6.2 (DXS304) have become available. Both markers are tightly linked to the fragile-X locus, but their location relative to the fragile site was not known with certainty. We have tested these new markers in a multipoint linkage analysis of 26 fragile-X families typed for DXS105 as a proximal marker and DXS52 as a distal marker. Our results establish the order DXS105-DXS369-fra(X)-DXS304-DXS52, which is in agreement with physical mapping results.

DNA↗
PubMedDate not supplied

Parental origin of the fra(X) gene is a major determinant of the cytogenetic expression and the CGG repeat length in female carriers.

The fragile X [fra(X)] syndrome is the most frequent form of inherited mental retardation, and co-segregates with a fragile site at Xq27.3 as well as with insertion of a variable number of trinucleotide repeats in the 5'-end of the FMR-1 gene. As the fra(X) gene is transmitted by females as well as males, we have investigated whether the parental origin of the fra(X) gene has an effect upon the cytogenetic expression and CGG repeat length. An increased fragment length of 0.2-0.6 kb appeared to be associated with a very low expression or even complete absence of the fragile site as well as with a normal phenotype, and was seen mostly in cases of paternal inheritance. However, in most female carriers with the maternally inherited fra(X) gene we found dispersed fragments ranging from 1.4-6.5 kb or even complete absence of a hybridization signal. Within the group of female carriers with the maternally inherited fra(X) gene we found a statistically significant correlation between the level of the cytogenetic expression and the PstI restriction fragment length encompassing the CGG repeat. These data can be taken as indirect evidence that CGG repeat length and cytogenetic expression are causally related.

Cytogenetics↗
PubMedDate not supplied

High prevalence of the fra(X) syndrome cannot be explained by a high mutation rate.

The overall prevalence of the fragile X [fra(X)] mutation, as determined by population studies, is approximately 1 in 850 [Gustavson et al., 1986; Webb et al., 1986]. This prevalence suggests a very high mutation rate which, in turn, suggests that many patients have to represent sporadic cases. In order to obtain an accurate estimate of the proportion of sporadic cases, we performed genealogic, cytogenetic and DNA linkage studies as well as direct analysis of the CGG repeat in relatives of 84 fra(X) probands. We did not find any evidence for the presence of sporadic cases. In 11 probands consanguinity could be proven by the detection of common ancestors, in 5 related families up to 9 generations ago. In the other 6 related families the mutation could be traced back 4-6 generations. In 3 or more generation families we were able to demonstrate that half of the probands carried the grandpaternal fra(X) gene. These results imply that rather than a high mutation rate, both Normal Transmitting Males (NTM's) and mentally normal female carriers contribute considerably to the high prevalence of the fra(X) syndrome.

Female↗
PubMedDate not supplied

Expression of platelet-derived growth factor in and around intrastriatal embryonic mesencephalic grafts.

The expression of platelet-derived growth factor (PDGF) was investigated in the embryonic donor tissue and surrounding host brain before and after intracerebral transplantation in a rat model of Parkinson's disease (PD). Ventral mesencephalic tissue from E13-E15 rat embryos was dissociated and implanted into adult rats with unilateral lesions of the mesostriatal dopamine system. Immunohistochemical studies showed that the majority of the grafted cells were PDGF-positive at early time points after grafting. However, the immunostaining gradually decreased, and had disappeared almost completely 3 wk after transplantation. These results were in agreement with in situ hybridization data demonstrating detectable levels of mRNA for PDGF chains in graft cells after 1, but not after 6 wk. In contrast, a large number of PDGF-immunoreactive cells was observed in the host brain adjacent to the grafts from 1 wk after transplantation, and increasing with time. Increased expression of PDGF was also observed in response to a sham-operation (injection of vehicle), although the number of PDGF-positive cells seemed lower than after grafting of embryonic tissue. Double immunofluorescence labeling of these cells with an anti-glial fibrillary acidic protein (GFAP) antiserum and a monoclonal antibody against PDGF B-chain, indicated that the PDGF-positive cells were astrocytes. The dynamic expression of PDGF in and around intrastriatal embryonic mesencephalic implants has several, potentially important, implications for graft survival and function. Glial cells could utilize the elevated levels of PDGF to proliferate in a reactive gliosis, and PDGF might also augment immune responses. It is also possible that PDGF increases the survival of, and promotes neurite outgrowth from, grafted dopaminergic neurons.

Analysis of Variance↗
PubMedDate not supplied

Platelet-derived growth factor receptor expression after neural grafting in a rat model of Parkinson's disease.

Platelet-derived growth factor (PDGF) has trophic effect on dopaminergic neurons in vitro. We have previously shown dynamic changes in the expression of PDGF in embryonic mesencephalic grafts and surrounding host striatal tissue following intracerebral transplantation in a rat model of Parkinson's disease. In this study the expression of the PDGF receptors was examined in the same model using immunohistochemistry. Most ventral mesencephalic (VM) cells from E13-E15 rat embryos possessed both PDGF alpha- and beta-receptors before implantation. Double immunofluorescence staining revealed that about 10% of the cells also expressed tyrosine hydroxylase (TH). The PDGF alpha-receptor was detectable in the graft up to 1 wk after transplantation but had disappeared at 3 wk. In the host tissue, scattered glial cells were positive for the alpha-receptor but the expression was unchanged following transplantation. The beta-receptor expression almost completely disappeared from the grafted tissue by 4 h following transplantation, and only a few cells of the host striatum showed immunoreactivity. However, after 3 wk beta-receptor positive cells were again detectable in the graft. These cells appeared to be endothelial cells as identified by an antibody against von Willebrand's factor. Our data suggest that PDGF might act locally on embryonic dopaminergic cells in an autocrine or juxtacrine manner before and shortly after transplantation, and on surrounding glial cells in a paracrine manner after transplantation. Furthermore, PDGF-BB might influence neovascularization in the graft.

Animals↗