Biomedical subjects

A Smits

Publications and source records attributed to A Smits.

At least 37 records · Page 2Linked to original sources

PubMed1997

Rapid antibody test for diagnosing fragile X syndrome: a validation of the technique.

To date, the identification of patients and carriers of the fragile X syndrome has been carried out by DNA analysis by means of the polymerase chain reaction and Southern blot analysis. This direct DNA analysis allows both the size of the CGG repeat and methylation status of the FMR1 gene to be determined. We have recently presented a rapid antibody test on blood smears based on the presence of FMRP, the protein product of the FMR1 gene, in lymphocytes from normal individuals and the absence of FMRP in lymphocytes from patients. Here, we have tested the diagnostic value of this new technique by studying FMRP expression in 173 blood smears from normal individuals and fragile X patients. The diagnostic power of the antibody test is "perfect" for males, whereas the results are less specific for females.

Antibodies, Monoclonal↗

PubMed1997

At least nine cases of trisomy 11q23-->qter in one generation as a result of familial t(11;13) translocation.

Carriers of balanced reciprocal translocations may have a (high) risk for producing liveborn children with an unbalanced karyotype. We report a large family in which a translocation between the long arm of chromosome 11 and the short arm of chromosome 13 is segregating in at least five generations. During the course of our study 15 carriers of the balanced translocation were identified and nine cases of partial trisomy of the long arm of chromosome 11 were detected during pre- and postnatal studies. Several of the patients were thoroughly clinically examined and compared with similar published cases.

Adult↗

PubMed1996

Synergistic inhibitory effects of interferon-alpha and 5-fluorouracil in meningioma cells in vitro.

We have investigated the effects of interferon-alpha (IFN-alpha) and 5-fluorouracil (5-FU) on meningioma cells in two different culture systems, evaluated by the uptake of radiolabelled methionine. With both IFN-alpha and 5-FU an inhibitory effect on the uptake of radiolabelled methionine by the meningioma cells was demonstrated, and we found a synergistic inhibitory effect with a combination of IFN-alpha and 5-FU. To obtain a maximal inhibition of cell metabolism without causing cell toxicity, we were able to decrease the dose of 5-FU by simultaneously adding IFN-alpha. Our results suggest that a combined treatment of IFN-alpha and 5-FU may be a successful alternative for patients with inoperable meningiomas. A novel in vitro positron emission tomography technique was used for the study of metabolic changes in tumour cells caused by drug treatment, which is complementary to conventional cell culture techniques.

Adult↗

PubMed1996

Evaluation of general practice care by chronically ill patients: effect of the method of administration.

BACKGROUND: Although the patient survey has become a popular method for learning about patients' views and experiences, little attention has been paid to the validity and feasibility of different survey methods. OBJECTIVE: A study was undertaken to compare handing out written questionnaires to chronically ill patients who consecutively visited the general practice with mailing questionnaires to chronically ill patients who were sampled from the patient register. METHOD: Patient surveys were performed in eight general practices in The Netherlands, applying both methods of administering the questionnaire to patients in each practice (n = 345). RESULTS: The response rate was 63% in the mail survey and 72% in the hand-distributed survey. The sample composition was almost equal, except that patients in the hand-distributed survey more often reported having 'a different chronic disease.' The item-response for each aspect of care was similar in both methods of administration. CONCLUSION: Patients in the mail survey tended to use the extreme categories on the scale for certain aspects of care more often than patients in the hand-distributed survey, but the overall trend was not significant.

Adolescent↗

PubMed1996

Enzyme polymorphisms in the Anopheles gambiae (Diptera:Culicidae) complex related to feeding and resting behavior in the Imbo Valley, Burundi.

A cellulose acetate electrophoresis system was used to study the Anopheles gambiae complex at 2 villages in Central Imbo Valley and at 1 village in South Imbo Valley (Burundi). In South Imbo, only An. gambiae Giles sensu stricto was present. In the drier Central Imbo, the dominant species was An. arabiensis Patton (97.5%); An. gambiae s.s. represented only 2.5%. Both species were separated readily by Odh and Mpi, because they did not share alleles at those loci. Indoor resting An. gambiae s.s. from South Imbo differed significantly from outdoor resting females at 2 Ioci, Mpi, and Got-2. In Central Imbo, total An. arabiensis did not differ between adjacent villages. Endophagic An. arabiensis significantly differed at loci alpha-Gpd, and Idh-1 between the 2 villages, whereas no difference was observed between exophagic females. Allelic and genotypic frequencies at the locus Mdh-2 were significantly different between indoor and outdoor biting An. arabiensis. Active choice for the best place to bite or to rest seemed to be associated with specific genotypes. The Nei genetic distance values were typical of conspecific populations, ranging from 0.154 to 0.160 between An. gambiae s.s. and An. arabiensis. Even though vector populations were structured at spatial and behavioral levels, they were panmictic, and thus selection of exophilic or exophagic vectors, or both, by insecticide pressure is not likely to occur.

Animals↗

PubMed1996

Indicators of the quality of general practice care of patients with chronic illness: a step towards the real involvement of patients in the assessment of the quality of care.

OBJECTIVE: To develop a list of indicators of the general practice care of people with chronic illnesses considered important by both patients and practitioners and to identify the indicators that are considered relevant for patient assessment of health care quality. DESIGN: Qualitative study with focus group interviews and a written consensus procedure. SETTING: General practice in the Netherlands in 1993. SUBJECTS: 34 patients with chronic illness, mostly members of patient organisations, and 19 general practitioners with expertise in either chronic disease management or experience with patient surveys. MAIN MEASURES: Aspects of general practice care considered important for the delivery of good quality care that emerged from focus group interviews; the relevance of evaluations of 41 aspects of care for patients explored through the written consensus procedure. Those aspects of general practice care agreed to be both important and relevant by patients and general practitioners were considered to be suitable indicators for patient assessment of the quality of care. RESULTS: Patients and general practitioners differed to some extent in their assessment of the aspects of care that they considered important for quality. They agreed that most indicators of care that related to the ¿doctor-patient relation¿ and to ¿information and support¿ were relevant and therefore suitable as indicators for patient assessment of health care quality. There was less agreement about the relevance of indicators of ¿medical and technical care,¿ ¿availability and accessibility,¿ and ¿organisation of services.¿ CONCLUSIONS: Several indicators of the quality of general practice care of patients with chronic illness were thought to be suitable for the patient assessment of healthcare quality, but other indicators were not, mainly because of reservations by general practitioners. IMPLICATIONS: Qualitative methods can contribute to the selection of indicators for assessment of the quality of health care in areas where scientific evidence is limited or where patients' and providers' preferences are particularly important.

Chronic Disease↗

PubMed1996

Coexpression of platelet-derived growth factor alpha and beta receptors on medulloblastomas and other primitive neuroectodermal tumors is consistent with an immature stem cell and neuronal derivation.

Medulloblastomas and related childhood primitive neuroectodermal tumors (PNET) are currently thought to originate from a multipotent stem cell that can give rise to a variety of different tumor types, representing different lines of differentiation and stages of maturation of the original stem cell. The proliferation and differentiation of different cell types in the central nervous system are influenced by growth factors, such as platelet-derived growth factor (PDGF). In this study, we investigated the expression of the two types of PDGF receptors, alpha and beta, on 14 cases of PNET by immunohistochemistry and in situ hybridization. To characterize the tumor cells according to their differentiation and maturation, we performed immunohistochemistry with Ab against several members of the intermediate filament family, such as neurofilament, glial fibrillary acidic protein, vimentin, and the embryonal marker nestin. For the cerebral PNET, we found that the phenotype of multidirectional differentiation (with coexpression of neurofilament, glial fibrillary acidic protein, vimentin, and in some cases nestin) was associated with the expression of both PDGF alpha and beta receptors on the tumor cells. Medulloblastomas (i.e., cerebellar PNET), however, often showed the phenotype of partially committed neuron-like precursor cells, and this was associated with the predominant expression of PDGF alpha receptors on the tumor cells. Our findings show that the PDGF alpha receptor, previously known to play a role in the normal development of cells of the glial lineage, either exclusively or in combination with the PDGF beta receptor, is expressed on tumor cells of neuronal derivation. This "aberrant" expression of PDGF alpha receptors on PNET may reflect a feature of the malignant phenotype of these tumors. Further studies are needed to study the biologic effects of PDGF-A and its receptor in PNET.

Brain Neoplasms↗

PubMed1995

Detection of TP53 gene mutation in human meningiomas: a study using immunohistochemistry, polymerase chain reaction/single-strand conformation polymorphism and DNA sequencing techniques on paraffin-embedded samples.

Mutations in the TP53 tumor suppressor gene have been studied in different types of brain tumors. Little is known about this genetic event in human meningioma, a mostly benign tumor. To investigate the frequency of TP53 gene mutations in human tumors derived from meningeal tissues, paraffin-embedded tissues from 30 cases (including 2 malignant and 4 atypical meningiomas, as well as 2 hemangioblastomas and 3 hemangiopericytomas) were screened by immunohistochemistry. Polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) and direct DNA sequencing were thereafter performed in selected cases. Nuclear p53 staining was not seen in any of the 19 benign meningiomas tested, while atypical meningiomas, hemangioblastomas, and hemangiopericytomas displayed nuclear staining in a subpopulation of tumor cells in 4 out of 5, 2 out of 2, and 3 out of 3 cases, respectively. One malignant meningioma showed an intense nuclear staining and a band shift in SSCP. In this case, we identified a mutation in the TP53 gene at codon 161 changing GCC to ACC and resulting in an alteration of alanine to threonine in this position. Our results indicate that TP53 gene mutation may be considered as a marker for malignant transformation in meningioma. p53 immunoreactivity, even in the absence of detectable gene mutation, is also associated with atypia and does not appear in regular benign meningiomas.

Adult↗

PubMed1995

Linkage analysis in a Dutch family with X-linked recessive congenital stationary night blindness (XL-CSNB).

Linkage analysis has been performed in a large Dutch pedigree with X-linked recessive congenital stationary night blindness (CSNB) by utilizing 16 DNA markers from the proximal short arm of the human X chromosome (Xp21.1-11.2). Thirteen polymorphic markers are at least partially informative and have enabled pairwise and multipoint linkage analysis. For three loci, i.e. DXS228, the monoamine oxidase B gene and the Norrie disease gene (NDG), multipoint linkage studies have yielded maximum lod scores of > 3.0 at a recombination fraction of zero. Analysis of recombination events has enabled us to rule out the possibility that the underlying defect in this family is allelic to RP3; the gene defect could also be excluded from the proximal part of the region known to carry RP2. Linkage data are consistent with a possible involvement of the NDG but mutations in the open reading frame of this gene have not been found.

Chromosome Mapping↗

PubMed1995

Intestinal methanogenesis in primates--a genetic and evolutionary approach.

The presence of significant numbers of intestinal methanogens among vertebrates does neither depend on elaborated morphological structures nor on predominantly plant-based diets. Phylogenetic rather than dietary restrictions limit the occurrence of methanogenic bacteria also in the hindguts of primates. The Old-World monkeys are methanogenic--with the only exceptions of Cheirogaleid lemurs and bush-babies. In contrast, among New World monkeys the lack of intestinal methanogens is observed frequently in capuchins and marmosets. Since the absence of methanogens does not parallel distinct morphological, physiological, or ethological characteristics, it is likely that methanogenesis depends on a hereditary predisposition. In humans, methane-producers account for approximately 50% of the European populations. In this study, 56 individuals belonging to 5 families were studied for the occurrence of methane in the breath. The results of this screen are compatible with the assumption that the trait "methane emission" segregates as an autosomal, dominant character. Our findings suggest a high specificity of the symbiosis between primates and methanogenic bacteria. Therefore, the persistence of significant numbers of methanogens in the hindgut might be facilitated by a specific receptor for methanogenic bacteria.

Animals↗

PubMed1994

Prediction of mental status in carriers of the fragile X mutation using CGG repeat length.

For genetic counseling in fragile X (fra(X)) families, it is important to know the diagnostic impact of the CGG repeat length in carriers of the fragile X mutation. We have analyzed the CGG repeat length in 106 males and 73 females who had inherited the maternal fra(X) mutation. The sensitivity, specificity, and predictive value of the CGG repeat analyses, as measured on Southern blots of PstI/EcoRI digests, were calculated. In males the sensitivity, specificity and negative predictive value were 99%, 100% and 94%; respectively. In females the specificity (60%) and, consequently, the positive predictive value (82%) was reduced. Therefore, it remains impossible to predict accurately whether a female fetus demonstrating a full mutation will be affected. On the other hand, the negative predictive value of the CGG test in females was 100%. We have no evidence, as yet, that for female carriers with the full mutation, cytogenetic analysis is of additional value to predict the mental status. However, we have observed one mentally retarded fra(X) case with extreme mosaicism in which a typical premutation fragment was the predominant DNA species. Therefore, until more data and better DNA tests are available, we would like to advocate additional cytogenetic investigation if in a fetus a CGG repeat length in the premutation range is found.

Blotting, Southern↗

PubMed1994

Quality judgements by patients on general practice care: a literature analysis.

Patient report seems to be a workable method for quality assurance. For the purpose of the development of such a method, a review was made of 40 studies into patient judgements on general practice care. Apparently, many aspects of care are only rarely included in patient report and the patients themselves are hardly ever involved in selecting these aspects. Furthermore, there appears to be a large variety in the methods that are used. The conclusion must be that in the field of general practice care only little progress has been made in the development of patient report as a method for quality assurance.

Family Practice↗

PubMed1993

PDGF-BB exerts trophic activity on cultured GABA interneurons from the newborn rat cerebellum.

Platelet-derived growth factor (PDGF) is a well known mitogen for mesenchyme-derived cells and glial cells. Its presence in neuronal cells of the central nervous system has only recently been described. We have shown earlier that neurons of newborn rat brains in culture express PDGF beta-receptors and that PDGF-BB, a homodimer of PDGF B-chain, increases survival and promotes neurite outgrowth of newborn cerebellar cells (Smits et al., Proc. Natl Acad. Sci. USA, 88, 8159-8163, 1991). In this study, the effects of PDGF on early postnatal rat cerebellar cells were further explored. By using chemically defined serum-free medium, we have established primary cell cultures of rat cerebella (postnatal day 4-5) containing 70-80% neuronal cells. During the first 10 days in vitro, no difference in total cell number was found between PDGF-BB-treated and untreated cultures. After this time period, however, increased survival of the PDGF-BB-treated cells was found. Within the first 10 days in vitro, the addition of PDGF-BB to the cultures resulted in a relative increase in survival of interneurons expressing glutamic acid decarboxylase (GAD), the GABA biosynthetic enzyme. Moreover, addition of PDGF-BB in the untreated cell culture resulted in a rapid increase of GAD mRNA. These results show that PDGF-BB acts as a trophic factor on GABAergic interneurons of the cerebellum by up-regulating GAD synthesis and prolonging the survival of these cells. Furthermore, in situ hybridization revealed that there are scattered cells present in the early postnatal cerebellum that express PDGF beta-receptor mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Platelet-derived growth factor promotes survival of rat and human mesencephalic dopaminergic neurons in culture.

The effect of two isoforms of platelet-derived growth factor (PDGF), PDGF-AA and PDGF-BB, was tested on dissociated cell cultures of ventral mesencephalon from rat and human embryos. PDGF-BB but not PDGF-AA reduced the progressive loss of tyrosine hydroxylase- (TH)-positive neurons in rat and human cell cultures. The mean number of TH-positive cells in the PDGF-BB-treated rat culture was 64% and 106% higher than in the control cultures after 7 and 10 days in vitro, respectively. Corresponding figures for human TH-positive neurons were 90% and 145%. The influence of PDGF-BB was specific for TH-positive neurons and not a general trophic effect, since no change of either total cell number or metabolic activity was found. In PDGF-BB-treated cultures of human but not rat tissue the TH-positive neurons had longer neurites than observed in control or PDGF-AA-treated cultures. These data indicate that PDGF-BB may act as a trophic factor for mesencephalic dopaminergic neurons and suggest that administration of PDGF-BB could ameliorate degeneration and possibly promote axonal sprouting of these neurons in vivo.

Animals↗

PubMed1992

Differential effects of platelet-derived growth factors on fetal hippocampal and cortical grafts: evidence from intraocular transplantation in rats.

Effects of platelet-derived growth factor-AA (PDGF-AA) and platelet-derived growth factor-BB (PDGF-BB) on developing parietal cortex (E16) and hippocampal (E18-E19) grafts were studied using the in vivo method of intraocular transplantation. Survival and growth of grafts in the anterior eye chamber of adult host rats under the influence of regular treatments with 0.5 ng (in a 100 ng/ml concentration) PDGF-AA or PDGF-BB was followed and compared to those receiving vehicle solution alone (0.5 mg HSA/ml Hanks). Both PDGF-AA and PDGF-BB increased the volume of transplanted cortical grafts. PDGF-BB also exerted trophic effects on grafted hippocampal tissue whereas PDGF-AA seemed to inhibit hippocampal growth. Histological and immunohistochemical studies revealed an increase in the density of astroglial elements in PDGF-AA- and PDGF-BB-treated cortical grafts whereas the PDGF-AA- and PDGF-BB-treated hippocampal grafts maintained a cytoarchitecture closely resembling that of control grafts. These findings support in vitro experiments showing that developing glial cells are stimulated by PDGFs and we further propose regional differences of action of PDGFs in the developing central nervous system.

Animals↗

PubMed1992

Assessing the symptoms, anxiety and practical needs of HIV/AIDS patients receiving palliative care.

We report the work of two community teams who care for people with AIDS/HIV related illness, the characteristics of patients referred, and the impact of the teams on four aspects of quality of life. Data was collected on 140 patients (85 St. Mary's Home Support Team, 55 Bloomsbury Community Care Team) who were referred to and remained in the care of these teams until death. All patients were male, mean age 37.9 years, 116 were homosexual. Most referrals were from genito-urinary medicine clinics (48%) or AIDS wards (41%). There was a wide range of reasons for referral. At referral 62% were in hospital and 35% at home. Mean time in care was 31 weeks 5 days. Fifty-seven per cent died in hospital, 22% at home and 21% in a hospice. The Support Team Assessment Schedule (STAS), consisting of 17 items of care, was used by the teams to measure aspects of quality of life. Throughout care until death four STAS items: pain control, symptom control, patient anxiety and practical aid are reported in detail. Symptom control was a commonly severe problem at referral and although the teams had some success in improving this item it remained a serious problem throughout care. Patient anxiety, also a commonly severe problem at referral, improved significantly throughout care. Pain control was less commonly severe at referral and improved significantly throughout care. Practical aid, in contrast, was rarely a severe problem at any stage of care.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Urinary incontinence in women and the effects on their lives.

The aim of this study was to assess and analyse the effects of urinary incontinence in women and to examine the relationship between these effects and the type and severity of incontinence. 110 women aged 20 to 65 who had reported urinary incontinence to their general practitioners underwent a comprehensive history and a complete urodynamic evaluation. The reported consequences of incontinence included low self-esteem, changing life-style in order to avoid potentially embarrassing situations, and all kinds of practical worries. Fear of the odour played the most important part and was mentioned as being the worst effect in 40% of the cases. Most of the women appeared to cope adequately with the unpleasant aspects of this condition. More effects were associated with urge incontinence than with stress incontinence, while there was a significant relationship between the objective severity of the incontinence and its psychosocial impact. The main conclusion is that although urinary incontinence is not a severe physical disability, a spectrum of psychological problems is associated with it. In particular, the fear of being smelt was of the utmost importance.

Adaptation, Psychological↗

PubMed1992

Platelet-derived growth factor is angiogenic in vivo.

PDGF receptors have recently been found to be expressed in microvascular endothelium in vivo under circumstances of endothelial cell activation and angiogenesis suggesting that PDGF may have a direct effect on endothelial cells. We have tested the angiogenic activity of PDGF-AA and -BB homodimers in the chick chorioallantoic membrane in vivo. PDGF-BB was found to consistently induce an angiogenic response whereas PDGF-AA was less active. Morphological analyses revealed that there was little inflammation associated with this response but an increase in vessel density suggested a direct effect of PDGF on embryonic chorioallantoic endothelial cells. In vitro, PDGF-BB was found to be more potent than PDGF-AA in stimulating the chemotaxis of rat brain capillary endothelial cells. This is consistent with a direct effect of PDGF on endothelial cells. Thus, this novel angiogenic activity of PDGF has implications for several developmental and pathological events in which PDGF, particularly the B-chain, is expressed.

Allantois↗