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Biomedical subjects

E de Vries

Publications and source records attributed to E de Vries.

At least 37 records · Page 2Linked to original sources

Monitoring stage-specific trends in melanoma incidence across Europe reveals the need for more complete information on diagnostic characteristics.

Cutaneous malignant melanoma has been characterized by rapid and steady increases in incidence and mortality in white populations. Some reports mentioned declining trends in the mean thickness of these tumours, but other studies suggested a stable incidence of thick melanomas. The aim of this study was to describe the stage distribution of melanomas across Europe, with particular reference to temporal trends. Twenty-three cancer registries provided data sets containing information on stage and histology, 21 of which were used for a general description and nine for trends analyses. Despite a preponderance of missing data, interesting patterns emerged: a less favourable stage distribution in populations with relatively low incidence, but high case-fatality rates, and a favourable trend in stage and histology distribution over time, including a shift from later to earlier stages in recent years. Early detection campaigns raising awareness for thin lesions can potentially improve melanoma survival rates. Monitoring of stage-specific trends in melanoma incidence can assess the impact of such interventions. This paper demonstrates the potential utility of high-quality, timely cancer registry data in pursuing such public health objectives and addresses the need for more complete information on diagnostic features of melanoma patients. This will allow more informative evaluations of preventive strategies.

Adult↗

Rising trends in the incidence of and mortality from cutaneous melanoma in the Netherlands: a Northwest to Southeast gradient?

The aim of this study was to determine characteristics of the trends in incidence of and mortality from cutaneous malignant melanoma in The Netherlands. We used incidence data from the Netherlands Cancer Registry since 1989 and the causes of death registry of Statistics Netherlands since 1950. Data were age-adjusted and age-specific rates were calculated. Age-period-cohort modelling was applied to the mortality data. Between 1989 and 1998, age-adjusted incidence rates increased, mainly among those aged 45 years and older. Incidence rates were highest in the North-West and lowest in the South-East. Mortality rates increased in all age-categories, but more so among males than females. For women, an age-period model fitted the data, with decreasing relative risks after 1972. Age-period-cohort models were needed for males. The most likely explanation for the higher incidence is increasing intermittent over-exposure to ultraviolet (UV) radiation. The regional differences in melanoma incidence rates would correspond with host characteristics opportunities for and recreational exposure. Melanomas were detected at earlier stages in females, possibly explaining the flattening out of the female mortality rates.

Adult↗

Cooperia punctata trickle infections: parasitological parameters and evaluation of a Cooperia recombinant 14.2 kDa protein ELISA for estimating cumulative exposure of calves.

Three groups of four calves each were trickle infected with three different levels of Cooperia punctata: 310 (group A), 1250 (group B) and 5000 (group C) third stage infective larvae (L3) twice a week over a 17-week period. Group D was the non-infected control group. Parasitological parameters as faecal egg counts (epg), worm burdens, size of worms and number of eggs per female were collected and the differences between the groups compared. Serological analyses were also conducted to investigate the efficiency of a recombinant C. oncophora CoES 14.2kDa protein in an ELISA to detect C. punctata antibodies. Group C had higher faecal egg counts until week 9 when the values decreased to those in group B. Mean faecal egg counts in group A were always lower than in the two other infected groups. The worm burdens were highest in group C, and lowest in group A, although the number of worms as a percentage of total larval intake was higher for the lower group. The mean length of the worms was shorter and the number of eggs per female lower for group C than for both other groups. ELISA using the CoES 14.2kDa proved to be efficient in measuring C. punctata antibodies. For group C it took 4 weeks to get increased levels of antibodies and this was one and 2 months more for groups B and A, respectively. Overall, there was a congruent relation between C. punctata antibodies and the cumulative exposure to the three different levels of trickle infections.

Animals↗

Differential expression of thymus and activation regulated chemokine and its receptor CCR4 in nodal and cutaneous anaplastic large-cell lymphomas and Hodgkin's disease.

Recent studies demonstrated that Hodgkin/Reed-Sternberg (H/RS) cells in Hodgkin's disease (HD) express thymus and activation-regulated chemokine (TARC), whereas reactive lymphocytes surrounding H/RS cells express its ligand, CC-chemokine receptor 4 (CCR4). Because in vitro studies showed that CCR4 expression is a marker for lymphocytes bearing a T-helper 2 (Th2) phenotype, it was suggested that expression of TARC is a new immune escape mechanism in HD. To find out whether this mechanism might also be operative in CD30+ malignant lymphomas other than HD, TARC and CCR4 expression was investigated by immunohistochemistry on paraffin and frozen-tissue sections of 39 nodal CD30+ anaplastic large cell lymphomas (ALCL), including 27 ALK-negative and 12 ALK-positive ALCL, 25 primary cutaneous CD30+ ALCL, including 11 patients with lymphomatoid papulosis, and 31 cases of HD. TARC was expressed by the neoplastic cells in 12/27 (44%) nodal ALK-negative ALCL and all cases of classic HD, but not in nodal ALK-positive ALCL (0/12) and only rarely in primary cutaneous CD30+ ALCL (3/25). In contrast, CCR4 was expressed by the neoplastic cells in 9/9 cutaneous CD30+ ALCL, and in 9/15 (60%) nodal ALK-negative ALCL, but only in 1/4 (25%) nodal ALK-positive ALCL and not by the H/RS cells in HD (0/8). Apart from three cases of HD showing 10 to 15% CCR4-positive lymphocytes surrounding TARC-positive H/RS cells, CCR4-positive reactive T cells were few (<5%) in all other cases studied. Our results demonstrate a differential expression of TARC and CCR4 in different types of CD30+ malignant lymphomas. The small number of CCR4-positive reactive T cells in most cases studied argues against an important role of TARC expression in the evasion of antitumor responses.

Alkaline Phosphatase↗

Th1/Th2 cytokine imbalance in a family with hyper-IgE syndrome.

BACKGROUND: Hyperimmunoglobulin E (hyper-IgE) syndrome is a rare immunodeficiency characterised by recurrent skin and respiratory tract infections, skeletal and dental abnormalities, chronic eczema, and elevated serum IgE. We describe a family with four hyper-IgE syndrome patients (38, 37, 30 and 7 years old), in which we investigated the cytokine response to both specific and non-specific stimulation. METHODS: Whole blood from patients and volunteers was stimulated for either 24 or 48h at 37 degrees C with heat-killed Staphylococcus, C. albicans or a combination of IL-12 and IL-18. Cytokine concentrations in the plasma were measured by specific radioimmuno-assays or ELISA. RESULTS: Serum IgE ranged from 5,000 to 16,670 IU/ml, and neutrophil chemotaxis was normal in all four patients. Tumour necrosis factor, interleukin (IL)-1beta, IL-6 and IL-8 production after stimulation of whole-blood cultures with lipopolysaccharide or heat-killed S. aureus did not differ between the adult patients and four healthy controls. In contrast, when blood from patients and controls was stimulated with heat-killed S. aureus or C. albicans, a severe imbalance towards a Th2 phenotype was found, with 10- to 30-fold reduction in the IFNgamma/IL-10 ratios in the hyper-IgE syndrome patients. The IFNgamma production in the patients was less severely impaired when blood was non-specifically stimulated with a combination of IL-18 and IL-12. CONCLUSION: In this family with hyper-IgE syndrome, the imbalance in the Th1/Th2 cytokine production may have been involved in the pathogenesis of the recurrent infections and/or chronic eczema characteristic of this disease.

Adult↗

Physiological function of exopolysaccharides produced by Lactococcus lactis.

The physiological function of EPS produced by Lactococcus lactis was studied by comparing the tolerance of the non-EPS producing strain L. lactis ssp. cremoris MG1614 and an EPS producing isogenic variant of this strain to several anti-microbial factors. There was no difference in the sensitivity of the strains to increased temperatures, freezing or freeze-drying and the antibiotics, penicillin and vancomycin. A model system showed that EPS production did not affect the survival of L. lactis during passage through the gastrointestinal tract although the EPS itself was not degraded during this passage. The presence of cell associated EPS and EPS in suspension resulted in an increased tolerance to copper and nisin. Furthermore, cell associated EPS also protected the bacteria against bacteriophages and the cell wall degrading enzyme lysozyme. However, it has not been possible, so far, to increase EPS production using the presence of copper, nisin, lysozyme or bacteriophages as inducing factors.

Bacteriophages↗

Flow cytometric immunophenotyping in the diagnosis and follow-up of immunodeficient children.

From time to time, paediatricians are confronted with children who might suffer from a primary immunodeficiency disease. For practical purposes, these children can be divided into four main clinical categories: (1) a relatively large group of children with recurrent ear-nose and throat and lower respiratory tract infections, in some cases caused by deficiencies of antibodies or complement; (2) children with failure to thrive, intractable diarrhoea or an opportunistic infection which can be caused by a T-lymphocyte or combined immunodeficiency; (3) children with infections with pyogenic bacteria or fungi as seen in case of granulocyte/monocyte function deficiency; and (4) a small heterogeneous group of children with recurrence of particular infections. Also, acquired immunodeficiency becomes a more common problem in paediatric practice. Flow cytometric immunophenotyping of leucocytes appears to be an efficient and rapid tool in the diagnosis and follow-up of immunodeficient patients, supporting early recognition, before serious infections have compromised the child's general condition. This technique can now be performed in many hospitals. In this review, we give directions for the use of flow cytometric immunophenotyping of leucocytes in the diagnosis and follow-up of immunodeficient children according to the four main clinical categories.

Child↗

Common variable immunodeficiency (CVID) in a family: an autosomal dominant mode of inheritance.

BACKGROUND: Common variable immunodeficiency (CVID) is characterised by a late onset deficiency of immunoglobulins resulting in recurrent infectious and non-infectious ailments. Most cases are sporadic but occasional familial clustering has been described. We present an extensively affected family with CVID in three consecutive generations. METHODS: We conducted a study in this family to establish clinical phenotype, to clarify the mode of inheritance and to attempt to characterise the immune disturbance by determining immunoglobulin concentrations and B- and T-cell analysis. RESULTS: We describe six patients with CVID in three consecutive generations. In addition, we encountered 10 family members with dysimmunoglobulinemia. B-cell counts were normal, but T-cell analysis showed slightly abnormal results. CONCLUSIONS: The six cases of overt late onset hypogammaglobulinemia are compatible with an autosomal dominant mode of inheritance. The family members with dysimmunoglobulinemia may be at risk to develop overt CVID in the future, in view of the gradual course of progression of the disease in the clinically affected family members. B- and T-cell analysis are inconclusive though may support a possible defect in T-cell function to be involved. To further study this remarkable family and attempt to clarify pathogenesis, we are planning DNA linkage analysis in the near future.

Adult↗

Immunological investigations in children with recurrent respiratory infections.

Respiratory tract infections are common diseases in childhood. Most children with recurrent respiratory infections do not have an immunodeficiency. If they do, this is often due to an antibody deficiency. An important point in the investigation of a child with recurrent respiratory infections is to assess whether the child is thriving. If not, an underlying disease should be sought. Immunological investigations are useful if other, more frequent, underlying diseases have been ruled out. Early immunological screening is mandatory if there is a family history of immunodeficiency. In this review, a protocol is described which identifies children with severe antibody deficiency by simple screening tests before recurrent infections have caused irrepairable damage to the lungs. More elaborate tests are used to detect milder antibody deficiencies. These are reserved for those children in whom symptoms persist.

Child↗

Oral contraceptive use in relation to age at menopause in the DOM cohort.

BACKGROUND: We investigated the hypothesis that long-term use of oral contraceptives (OCs), in particular high-dose OCs, could postpone age at menopause. METHODS: Data was used from 8701 women who participated in a breast cancer screening programme in Utrecht (DOM-3 cohort), and who did not use hormone replacement therapy (HRT) or OCs in the 4 years prior to their last menses. Data on OC-use, menopausal status, age at menopause, year of birth, parity, smoking behaviour, socio-economic status, body mass index and age at menarche was available. Use of high-dose OCs has been defined in this study as OC-use before 1972. The data was analysed by means of linear regression and Cox's proportional hazards analysis. Women still menstruating, women with surgical menopause and women lost to follow-up were censored at their last known date of menstruation. Endpoint was the natural menopause (n = 4589). RESULTS: The use of high-dose OCs advanced the onset of menopause by approximately 1.2 months for every year of OC-use compared with no OC-use. High-dose OC-use for > or = 3 years, adjusted for confounding variables, increased the risk of earlier menopause compared with no OC-use (adjusted hazard ratio 1.12; 95% CI 1.03--1.21). The use of lower dose OCs did not increase the risk of earlier menopause (adjusted hazard ratio 1.00; 95% CI 0.91--1.09). CONCLUSIONS: These results are inconsistent with the hypothesis that long-term use of OCs could postpone the onset of menopause by inhibiting follicle depletion. Possible explanations are discussed.

Age Factors↗

[Immunology in medical practice. XXXIV. Screening for suspected immunodeficiency: Introduction].

A multistage laboratory protocol for the diagnosis of immunodeficiency is useful for the efficient identification of immunodeficient patients. The protocol presented in this article starts with the patient's clinical presentation. In the initial stages a low threshold for the performance of simple screening is applied, thus allowing early exclusion of potential immunodeficiencies, as well as identification of patients before serious infections have compromised their general condition. In the later stages, more elaborate tests leading to diagnosis and definitive classification are reserved for those few patients in whom the presence of an immunodeficiency is more probable. This definitive classification is important for the identification of carriers and for the genetic counselling of the family. The protocol described has been developed in cooperation with the Dutch national working parties of clinical immunologists (paediatric as well as internal medicine) and laboratory immunologists who are involved in diagnosing or treating patients with immunodeficiency.

Clinical Protocols↗

[Immunology in medical practice. XXXV. Screening of suspected immunodeficiency: diagnostic protocols for patients with opportunistic or recurrent severe infections, wasting and failure to thrive].

With a multistage laboratory protocol immunodeficiencies can be efficiently identified. The article presents a diagnostic protocol that consists of three schemes. Scheme 1 describes the diagnostic protocol for the large group of patients with recurrent pulmonary and ENT-infections, where an antibody deficiency can occasionally be found. Scheme 2 presents the diagnostic protocol for the much smaller group of patients with opportunistic infections, wasting or failure to thrive. Several of these patients suffer from a severe T-lymphocyte disorder. Early diagnosis and treatment is important for the prognosis in these patients. Scheme 3 shows the diagnostic protocol for patients with recurrent infections of surface areas and deeper organs; these patients may suffer from a phagocyte disorder.

Algorithms↗

Reconstitution of lymphocyte subpopulations after paediatric bone marrow transplantation.

We prospectively studied the reconstitution of lymphocyte subpopulations in a group of 22 children, who survived disease-free at least 6 months after allogeneic BMT for a haematological malignancy. Absolute counts of total lymphocytes, B lymphocytes, T lymphocytes, and CD4+ helper T lymphocytes reached the 5th percentile (p5) of age-matched reference values within 6 months after BMT in 15, 17, 7 and 2 patients, respectively. In particular, CD4+ helper T lymphocyte reconstitution was very slow. Unexpectedly, CMV reactivation had a profound positive influence upon the number of CD4+ helper T lymphocytes in the children. In five patients, absolute B lymphocyte counts above the 95th percentile were reached from 6 months after BMT onwards, mimicking normal ontogeny. Unlike normal ontogeny, the percentages of helper T lymphocytes expressing the 'naive' CD45RA isoform were low and those expressing the 'memory' CD45RO isoform were high in the first 3 months after BMT, as described before. Thereafter, the CD45RA:CD45RO ratio slowly normalised. Also, CD7 expression was absent on up to 90% of T lymphocytes in the first months after BMT, and on a steadily decreasing percentage thereafter, as recently described in adults. However, the absolute counts of CD45RO+/CD4+ and CD7-/CD4+ helper T lymphocytes did not change significantly. So, we found no evidence of peripheral expansion of previously primed donor-derived 'memory' T lymphocytes during the follow-up period which spanned 1-18 months after BMT. The absolute counts of 'naive' CD45RA+ helper T lymphocytes did not show a faster increase after BMT than in adults, despite the presumed presence of a non-involuted thymus in children. Bone Marrow Transplantation (2000) 25, 267-275.

Adolescent↗

Characterization of the beta-lactam binding site of penicillin acylase of Escherichia coli by structural and site-directed mutagenesis studies.

The binding of penicillin to penicillin acylase was studied by X-ray crystallography. The structure of the enzyme-substrate complex was determined after soaking crystals of an inactive betaN241A penicillin acylase mutant with penicillin G. Binding of the substrate induces a conformational change, in which the side chains of alphaF146 and alphaR145 move away from the active site, which allows the enzyme to accommodate penicillin G. In the resulting structure, the beta-lactam binding site is formed by the side chains of alphaF146 and betaF71, which have van der Waals interactions with the thiazolidine ring of penicillin G and the side chain of alphaR145 that is connected to the carboxylate group of the ligand by means of hydrogen bonding via two water molecules. The backbone oxygen of betaQ23 forms a hydrogen bond with the carbonyl oxygen of the phenylacetic acid moiety through a bridging water molecule. Kinetic studies revealed that the site-directed mutants alphaF146Y, alphaF146A and alphaF146L all show significant changes in their interaction with the beta-lactam substrates as compared with the wild type. The alphaF146Y mutant had the same affinity for 6-aminopenicillanic acid as the wild-type enzyme, but was not able to synthesize penicillin G from phenylacetamide and 6-aminopenicillanic acid. The alphaF146L and alphaF146A enzymes had a 3-5-fold decreased affinity for 6-aminopenicillanic acid, but synthesized penicillin G more efficiently than the wild type. The combined results of the structural and kinetic studies show the importance of alphaF146 in the beta-lactam binding site and provide leads for engineering mutants with improved synthetic properties.

Binding Sites↗