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Biomedical subjects

J de Groot

Publications and source records attributed to J de Groot.

At least 19 recordsLinked to original sources
PubMed1999

A physical complex of the Fanconi anemia proteins FANCG/XRCC9 and FANCA.

Fanconi anemia (FA) is a recessively inherited disease characterized at the cellular level by spontaneous chromosomal instability and specific hypersensitivity to cross-linking agents. FA is genetically heterogeneous, comprising at least eight complementation groups (A-H). We report that the protein encoded by the gene mutated in complementation group G (FANCG) localizes to the cytoplasm and nucleus of the cell and assembles in a molecular complex with the FANCA protein, both in vivo and in vitro. Endogenous FANCA/FANCG complex was detected in both non-FA cells and in FA cells from groups D and E. By contrast, no complex was detected in specific cell lines belonging to groups A and G, whereas reduced levels were found in cells from groups B, C, F, and H. Wild-type levels of FANCA/FANCG complex were restored upon correction of the cellular phenotype by transfection or cell fusion experiments, suggesting that this complex is of functional significance in the FA pathway. These results indicate that the cellular FA phenotype can be connected to three biochemical subtypes based on the levels of FANCA/FANCG complex. Disruption of the complex may provide an experimental strategy for chemosensitization of neoplastic cells.

Cell Fusion↗
PubMed1999

A single social defeat transiently suppresses the anti-viral immune response in mice.

Most of the studies dealing with effects of stress on anti-viral immunity have been carried out with stressors that are of long duration and that bear little relationship to the nature of the species. In this paper, we investigated the effect of a stressor mimicking real-life situations more closely, being social defeat of male mice, on anti-viral immunity. A single social defeat was applied at 3 or 6 days after inoculation with pseudorabies virus, a herpes virus. It appeared that lymph node cellularity, virus specific IL-2 and IFN-gamma production and lymphocyte proliferation were suppressed at 1 day after defeat, but these parameters restored to control values quickly thereafter. We conclude that the stress of a single social defeat evokes a transient immune suppression, which might have consequences if a pathogenic or lethal virus is involved.

Animals↗
PubMed1999

Effects of mild stress on the immune response against pseudorabies virus in mice.

Stress is a recognised problem in intensive pig husbandry, which might lead to changes in immune reactivity. To study the effect of stress on the development of an anti-viral immune response, we used a murine model in which mice were immunized with an attenuated strain of pseudorabies virus (PRV). The effect of two stress treatments, both relevant to intensive pig husbandry, on the development of the specific immune response against PRV was investigated. The stress treatments consisted of restraint, social isolation, and transport and they differed in predictability. The specific immune response against PRV, which developed in the draining lymph nodes, was measured by a lymphocyte proliferation assay and cytokine production assays. Our results showed that the unpredictable stress treatment had no effect on the development of the immune response against PRV in mice, whereas the predictable stress treatment actually hastened the immune response.

Animals↗
PubMed1998

Cross-reactivity patterns of contact-sensitizing methacrylates.

Methacrylates are well-known contact sensitizers with increasing frequency of contact leading to occupational skin disease. Here, we developed an animal model to facilitate studies on the sensitizing capacities and cross-reactivity patterns between four clinically most important allergens: methacrylate (MMA), 2-hydroxyethyl methacrylate (2-HEMA), 2-hydroxypropyl methacrylate (2-HPMA) and ethyleneglycol dimethacrylate (EGDMA). Inbred guinea pigs were immunized by ic injections of 300 microliters of 1.0 M methacrylate solutions in Freund's complete adjuvant into both flanks, both ears, and the neck. After 14 days open skin tests were performed with 50% MMA, 2-HEMA, or 2-HPMA or 10% EGDMA solutions in 40% DMSO in ethanol. Cross-reactivities were investigated 14 days later by skin testing with all four methacrylates. Using this newly developed protocol, strongly positive skin tests for methacrylates could be induced in almost all guinea pigs (MMA 26/26, 2-HEMA 16/18, 2-HPMA 15/16 and EGDMA 11/11). Whereas EGDMA induced only weak or infrequent cross-reactivities, 2-HEMA sensitization led to strong cross-reactions to all other methacrylates. Both MMA and 2-HPMA induced strong cross-reactivity to EGDMA but only weak to moderate reactivities to the other methacrylates. The absence of strong cross-reactions with monomethacrylates in EGDMA (dimethacrylate)-sensitized animals may be explained by the predominance of highly EGDMA-specific T-cells in these animals. In contrast, sensitization with MMA, 2-HEMA, and 2-HPMA would lead to recruitment of T-cells cross-reactive to the other monomethacrylates, according to their molecular similarities. The strong skin hypersensitivities observed for EGDMA in these latter groups are ascribed to enzymatic degradation into monomethacrylate compounds, notably 2-HEMA, at a rate sufficient to elicit cognate effector T-cells. The results of this study offer new insights in the development of methacrylate hypersensitivities and common cross-sensitization patterns in clinical practice.

Allergens↗
PubMed1998

Coming alive: the psychotherapeutic treatment of patients with eating disorders.

OBJECTIVE: To describe a dynamic psychotherapeutic approach specifically developed for women with eating disorders. METHOD: The developmental origins and psychological disturbances associated with eating disorders are outlined based on a review of the literature and the authors' observations. Principles from contemporary psychodynamic theories that focus on subjectivity and intersubjectivity are applied to the treatment of women with eating disorders and are illustrated with clinical vignettes. Theoretical models employed include intersubjective and relational theory, self psychology, and feminist psychodynamic theory. RESULTS: Relative unresponsiveness to a child's subjective experience and to child-initiated cues are thought to contribute to psychological disturbances among women with eating disorders. These disturbances include impairment in the sense of effectiveness, in the capacity to appreciate and tolerate emotions, and in the continuity and cohesiveness of self-experience. Self-imposed starvation, binge-purge episodes, and excessive exercise may act as psychic organizers in women with these vulnerabilities. An active psychotherapeutic approach with sustained interest in the patient's authentic subjective experience promotes the identification, organization, and integration of emotional experience and the consolidation of a more differentiated sense of self. CONCLUSION: In the psychotherapeutic treatment of women with eating disorders, a therapeutic posture of sustained empathic enquiry contributes to the patient's curiosity about her own subjective world. Feeling understood in a therapeutic relationship and feeling assisted in organizing and understanding one's subjective experience contributes to the gradual unfolding of the psychological sense of self.

Adult↗
PubMed1996

Reversal of orally induced T-cell tolerance by subcutaneous administration of interleukin-12 at the site of attempted sensitization.

Feeding of proteins causes peripheral T-cell tolerance, as revealed by reduced delayed-type hypersensitivity (DTH) reactivity after immunization. Using ovalbumin-fed mice, we studied whether putatively immunostimulatory cytokines could reverse this state of mucosal tolerance. It was found that local administration of neither IL-2, IFN-gamma, nor GM-CSF resulted in reversal of tolerance. In contrast, subcutaneous administration of IL-12 at the site of attempted immunization resulted in complete recovery of DTH reactivity. The dichotomy between the two Th1-stimulatory cytokines IFN-gamma and IL-12 was also reflected by different effects on ovalbumin-specific antibody isotypes. Although both IFN-gamma and IL-12 downregulated serum IgG1-levels in tolerant mice, suggesting decreased ovalbumin-specific Th2 function, only local administration of IL-12 led to increased serum Th1-related IgG2a levels. These results support the view that potentiation of Th1 effector function is critical for reversal of mucosal tolerance.

Adjuvants, Immunologic↗
PubMed1996

[Heart diseases in foals. A literature review exemplified by 2 case reports].

A review of the congenital and acquired heart diseases of foals is given on the basis of two patients. A 3-month-old foal with a history of collapse after exercise had a systolic murmur on all heart valves on both sides. Necropsy revealed endocarditis ulcerosa of the left atrioventricular valves. A 6-week-old foal with systolic murmur on the left atrioventricular valves and on the aorta showed, on ultrasonography, signs of endocarditis of the atrioventricular valves. This foal recovered after a long course of antibiotics.

Animals↗
PubMed1994

[Little difference in quality of life of dialysis patients in Utrecht and Willemstad].

OBJECTIVE: To assess and compare the quality of life of patients treated with haemodialysis and chronic ambulatory peritoneal dialysis (CAPD) in Utrecht and Willemstad, Curaçao. DESIGN: Transverse multicentre study. METHODS: All haemodialysis and CAPD patients in Utrecht and all haemodialysis patients in Curaçao under treatment for over 6 months were studied. The objective tests applied were the 'Nottingham health profile', the 'affect balance scale', the 'index of well-being' and the 'Amsterdam complaint profile'. Possible correlations between individual patient-related and treatment-related factors and biochemical variables were also investigated. RESULTS: The objective and subjective tests revealed only slight differences in quality of life in the three groups. In a few respects, the CAPD patients rated the quality of life slightly better. In the Utrecht group a positive relationship was seen between haematocrit (higher owing to treatment with erythropoietin) and plasma bicarbonate concentration, and the quality of life.

Cross-Cultural Comparison↗
PubMed1994

The risk of sensibilization and contact urticaria upon topical application of fumaric acid derivatives.

Systemic and sometimes topical therapy with fumaric acid (FA) and its derivatives is used in the treatment of psoriasis. Scattered data show that the topical application of these derivatives elicits side effects. Application of FA and some derivatives on the skin was accompanied by perilesional skin irritation, macular papular rashes and urticarial reactions. In order to determine the irritating and sensitizing properties of FA derivatives we used a cytotoxicity, flank irritation, ear swelling and guinea pig maximization test. The results of the cytotoxicity test demonstrated that dimethylfumarate (DMF) was the most toxic derivative. DMF induced also contact-urticarial reactions in contrast to mono-ethylfumarate (MEF). Challenge experiments with FA, MEF and DMF in MEF- and DMF-sensitized guinea pigs demonstrated that both MEF and DMF are moderate contact sensitizers. In DMF-sensitized animals cross-reactions with MEF were found. As DMF and MEF have cytotoxic, contact-urticarial and/or sensitizing properties, topical application should be avoided.

Administration, Topical↗
PubMed1992

Development of a concomitant nickel and chromium sensitization model in the guinea pig.

Although nickel allergy is the most frequent contact hypersensitivity in man, reports on successful nickel sensitization in experimental animals are scarce. Chromium hypersensitivity, on the other hand, is readily induced in guinea pigs. In this study we set out to obtain reproducible nickel sensitization in guinea pigs, in order to establish an animal model for immunospecific tolerance and desensitization studies in which two non-cross-reacting metal allergens, chromium and nickel, could be studied simultaneously. Strong and reproducible sensitization to nickel was achieved by injecting low amounts of Freund's complete adjuvant and nickel sulfate in a split-adjuvant procedure. Strong erythematous reactions were observed as early as 14 days after sensitization and could be elicited both by intradermal and open epicutaneous challenges. Optimal evaluation was with nickel sulfate administered epicutaneously in 40% dimethyl sulfoxide to enhance skin penetration. Hypersensitivity could be transferred with lymphocytes and not with serum. Sensitization procedures for nickel and chromium then could successfully be combined in a double sensitization procedure. With four different guinea pig strains no genetic restriction was observed for the induction of nickel or chromium sensitivity. However, for both metals a clear sex and age dependence was observed: female guinea pigs reached a higher degree of sensitization than males, whereas sensitization in young animals was relatively weak.

Administration, Cutaneous↗
PubMed1991

Cardiogenic shock after acute myocardial infarction. Incidence and mortality from a community-wide perspective, 1975 to 1988.

BACKGROUND: Cardiogenic shock resulting from acute myocardial infarction is a serious complication with a high mortality rate, but little is known about whether its incidence or outcome has changed over time. As part of an ongoing population-based study of acute myocardial infarction, we examined trends over time in the incidence and mortality rate of cardiogenic shock after acute myocardial infarction. METHODS: We studied 4762 patients with acute myocardial infarction who were admitted to 16 hospitals in the Worcester, Massachusetts, metropolitan area between 1975 and 1988. We determined the incidence of and short-term and long-term mortality due to cardiogenic shock in each of six years during this study period. RESULTS: The incidence of cardiogenic shock complicating acute myocardial infarction remained relatively constant, averaging 7.5 percent. Multivariate regression analysis that controlled for variables affecting incidence revealed significant though inconsistent temporal trends in the incidence of cardiogenic shock. As compared with the risk in 1975, the adjusted relative risk (with 95 percent confidence interval) was 0.83 (0.54 to 1.28) in 1978, 0.96 (0.63 to 1.48) in 1981, 0.68 (0.42 to 1.12) in 1984, 1.16 (0.70 to 1.92) in 1986, and 1.65 (0.99 to 2.77) in 1988. The overall in-hospital mortality rate among patients with cardiogenic shock was significantly higher than that among patients without this complication (77.7 percent vs. 13.5 percent, P less than 0.001). The in-hospital mortality among the patients with shock did not improve between 1975 (73.7 percent) and 1988 (81.7 percent). Long-term survival during the 14-year follow-up period was significantly worse among patients who survived cardiogenic shock during hospitalization than among patients who did not have shock (P less than 0.001). CONCLUSIONS: The results of this observational, community-wide study suggest that neither the incidence nor the prognosis of cardiogenic shock resulting from acute myocardial infarction has improved over time. Both in-hospital and long-term survival remain poor for patients with this complication.

Aged↗
PubMed1991

Proliferative capacity of mononuclear cells in the human lung.

In pulmonary sarcoidosis, a chronic granulomatous disorder with different stages of activity, the proliferative capacity of the alveolar mononuclear cells is unknown. To get a closer look at this proliferation we combined pulse labeling (by means of tritium thymidine incorporation and autoradiography) with an immunocytochemical staining assay. This assay revealed on one single slide simultaneously blue CD4+ lymphocytes, brown CD8+ lymphocytes and red macrophages. We were able to show that CD4+ as well as CD8+ lymphocytes were radiolabeled only in the active state of the disease. But macrophage proliferation occurred independently of the activity of the disease. In other words with this combination of techniques, it is possible to differentiate, on a single slide, three subsets of mononuclear cells, in combination with their proliferative behavior.

Autoradiography↗
PubMed1991

[Equine monocytic ehrlichiosis (EME), a review].

Serological surveys showed that equine monocytic ehrlichiosis (EME) occurs in the USA, Canada and Europe. The causative agent is Rickettsia Ehrlichia risticii, isolated for the first time in 1984. The clinical features of the disease are sluggishness, anorexia, colic and fever, possibly followed by watery diarrhoea. Complications of an infection with E. risticii are laminitis and abortion. Colitis of the ascending colon may be observed at autopsy. Following a positive serological diagnosis (IgM ELISA) of EME, treatment with oxytetracycline can be initiated. It is also important to restore the fluid and electrolyte balance by infusion. Prevention may be achieved by vaccination.

Animals↗
PubMed1991

A comparison of adinazolam and desipramine in the treatment of major depression.

Thirty-one patients with a DSM-III (R) diagnosis of Major Depression received adinazolam (n = 16) or desipramine (n = 15) during a 6 week double-blind randomized controlled trial. Both groups showed a significant decline in Hamilton Rating Scale for Depression scores (21.8 +/- 4.5 to 10.7 +/- 8.5 for adinazolam and 23.5 +/- 5.5 to 12.9 +/- 8.6) for desipramine. Melancholic and anxiety symptoms were reduced equally by both drugs. Initial sedation was the most common side-effect with adinazolam. Plasma levels of desipramine and hydroxy-desipramine correlated highly with oral dose after 3 weeks of treatment.

Adult↗
PubMed1991

Macrophage-T suppressor cell interference in the lungs of steroid-treated sarcoidosis patients.

In the bronchoalveolar lavage of sarcoidosis patients the mononuclear cell infiltrate was enumerated on T helper and suppressor lymphocytes as well as macrophages by means of a triple-staining assay on cytospin slides. As was seen on the slides, lymphocytes were often adhered very closely to macrophages. This phenomenon, many times described but not understood, was studied in a group of 13 sarcoidosis patients, of whom 7 received prednisolone treatment. It could be shown that treatment with the corticosteroid was followed by an increase in the percentage of suppressor lymphocytes adhered to macrophages. Second, the number of such alveolar T suppressor lymphocyte-macrophage aggregates was dramatically increased in the prednisolone-treated patients.

Adult↗
PubMed1990

Low allergenicity of clonidine impedes studies of sensitization mechanisms in guinea pig models.

During clinical trials, a clonidine transdermal device has been found to induce clonidine-specific allergic contact dermatitis in up to 25% of patients during a treatment period of 1 year. Using 3 different guinea pig strains, development was attempted of an experimental guinea pig model that would allow for in-depth studies into the mechanism of sensitization, and a possible role of transdermal device components. Transient low-level clonidine allergy could be obtained only in a minority of animals, with severe sensitization procedures departing from epicutaneous applications, combined with intradermal (adjuvant) FCA injections. Sensitization was not potentiated by additional booster procedures, including cyclophosphamide pretreatment, nor any of the putative cofactors (UV-treatments, C. parvum or acetaldehyde involvement) studied. These results suggest that the persistent skin contacts in man, with transdermal devices for sustained drug delivery, generate unique conditions favouring the development of allergic contact dermatitis, which are difficult to mimic in experimental animal models. Thus, clinical allergy may develop even to extremely weak sensitizing drugs that can be safely used orally, and escape most currently available predictive contact allergy animal models. Clinical studies remain unavoidable for studying factors that may reduce sensitization rates to more acceptable levels.

Administration, Cutaneous↗
PubMed1989

Histochemical characterization and functional significance of the hyperintense signal on MR images of the posterior pituitary.

MR imaging of the pituitary fossa characteristically shows a well-circumscribed area of high signal intensity in the posterior lobe on T1-weighted images. We used a combination of high-field MR, electron microscopy, and histologic techniques in experimental animals to determine whether the hyperintensity of the posterior lobe might be functionally related to hormone neurosecretory processes, and to attempt to establish its chemical nature. Histologic sections of a dog's pituitary gland processed with lipid-specific markers showed intense staining in the posterior lobe but not in the anterior lobe, thus documenting the location of fat in the posterior pituitary. Administration of vasoactive drugs known to influence vasopressin secretion to anesthetized cats produced changes in the volume of high-intensity signal in the posterior pituitary. Subsequent electron microscopy showed a significant increase in posterior lobe glial cell lipid droplets and neurosecretory granules in dehydration-stimulated cats. The data suggest that the pituitary hyperintensity represents intracellular lipid signal in the glial cell pituicytes of the posterior lobe or neurosecretory granules containing vasopressin. The volume of the signal may, in turn, reflect the functional state of hormonal release from the neurohypophysis.

Animals↗