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Biomedical subjects

J Knop

Publications and source records attributed to J Knop.

At least 19 recordsLinked to original sources
PubMed1992

Immunohistological and immunoelectron microscopic identification of TNF alpha in normal human and murine epidermis.

The presence, distribution and cellular localization of tumour necrosis factor-alpha (TNF alpha) were investigated in normal human and murine epidermis using immunohistological and immunoelectron microscopic methods with monoclonal and polyclonal antibodies. The immunostaining revealed an intercellular plasma membrane and cytoplasmic labelling of the epidermal keratinocytes, but no labelling of Langerhans cells, melanocytes and Merkel cells. Large amounts of TNF alpha were regularly found in the sebaceous glands. These findings demonstrate that epidermal keratinocytes and especially sebocytes produce and release TNF alpha and that this keratinocyte-derived cytokine may be important for the structural and functional homeostasis of normal epidermis.

Adult↗
PubMed1992

Contact allergens modulate the expression of MHC class II molecules on murine epidermal Langerhans cells by endocytotic mechanisms.

MHC class II molecules play an important role during the sensitization phase of allergic contact dermatitis. To study the influence of contact allergens on the expression of these molecules by murine epidermal Langerhans cells (LC), we performed a flow-cytofluorometric analysis of the Ia-antigen expression after in vivo application of contact allergens. A distinct decrease in the Ia-antigen expression of the entire LC population was noticed 3 h after in vivo application of the contact allergen 2,4-dinitrofluorobenzene (DNFB). This decrease was transient and balanced 24 h after in vivo application of DNFB. A downregulation was also detectable after in vivo application of the contact allergens 1-chloro-2,4-dinitrobenzene (DNCB), oxazolone, K2Cr2O7, 2,4,6-trinitrochlorobenzene (TNCB), and toxic concentrations of the irritant compound sodium dodecyl sulfate (SDS). In vitro studies showed that freshly prepared as well as 3-d cultured LC downregulated their Ia-antigen expression in the presence of DNFB, which was used as a model compound. This decrease was not inhibited by the MHC class II molecule transport-inhibitor brefeldin A nor by the ionophore monensin. The inhibition of receptor-mediated endocytosis with hypertonic media (0.45 M sucrose) abolished the DNFB-mediated downregulation of Ia-antigen expression. An accelerated clearance of cell-surface-expressed antibody-labeled IA molecules was detectable in the presence of DNFB. Internalization studies carried out with peroxidase-labeled anti-IA-antibody complexes showed remarkable alterations in the intracellular distribution of endocytosed material under the influence of subtoxic concentrations of DNFB, DNCB, K2Cr2O7, and TNCB. The irritant substance sodium dodecyl sulfate (SDS) influenced the intracellular distribution pattern of internalized material only when used in toxic concentrations. An augmented participation of MHC class II molecules in endocytotic processes is mediated by reactive substances like contact allergens and might contribute to the processing and presentation of these compounds.

Allergens↗
PubMed1992

Increased level of intracellular MHC class II molecules in murine Langerhans cells following in vivo and in vitro administration of contact allergens.

Treatment of murine Langerhans cells (LC) with contact allergens results in increased internalization of cell membrane constituents and therefore in depressed cell-surface expression of major histocompatibility complex (MHC) class II molecules during the first hours after haptenization. In this presentation we show that this downregulation of cell-surface-expressed Ia-antigens is accompanied by an augmentation of the intracellular pool of MHC class II molecules. Rat MoAb 2G9 was developed, which recognizes IA and IE molecules of the d-haplotype. This MoAb competes with the murine MoAb MK-D6 for binding sites to IAd-molecules. After blocking the cell-surface-expressed molecules with 2G9 and permeabilizing the cell membranes this allowed us to measure selectively the intracellular amount of IA molecules by double immunofluorescence staining and flow cytometric analysis. Cell-surface expression of IA molecules was found to be depressed but their internal pool was significantly elevated following in vivo treatment with the contact allergens DNFB, DNCB, oxazolone, and K2Cr2O7 for 3 h. In vitro culture of freshly prepared LC in the presence of 1 microgram/ml DNFB yielded similar results. Blocking of protein biosynthesis with cycloheximide did not prevent this intracellular class II accumulation. An augmented representation of internalized class II molecules in haptenized LC might play an important role in the presentation of contact allergens.

Administration, Cutaneous↗
PubMed1992

A novel monoclonal antibody to a distinct subset of cutaneous dendritic cells.

A monoclonal antibody was generated by immunizing rats with Langerhans cell (LC)-enriched epidermal cells obtained from BALB/c mouse earskin after epicutaneous application of the contact sensitizer 2,4-dinitrofluorobenzene (DNFB). The antibody 4F7 detects in normal mouse skin, few dermal cells showing the morphologic, phenotypic, and functional properties of accessory dendritic cells, but lacking Birbeck granules. The capacity to stimulate allogenic T cells in the mixed leucocyte reaction resembles that of freshly isolated LCs. After DNFB application, an increased number of 4F7+ dendritic cells are found in the dermis and, in addition, some labeled dendritic cells occur in the epidermis. Some of the latter cells exhibit cytoplasmic Birbeck granules. Remarkably, there is no increase of the 4F7+ cells in the regional lymph nodes after DNFB treatment. These data suggest that the 4F7 antibody labels distinct dendritic cells of the mouse skin that are involved in the mediation of contact sensitization and probably represent immature LCs.

Animals↗
PubMed1992

Induction of inflammatory cytokines in murine keratinocytes upon in vivo stimulation with contact sensitizers and tolerizing analogues.

In order to elucidate the role of keratinocytes (KCs) in the induction of contact sensitivity, we applied various contact sensitizers [2,4-dinitrofluorobenzene (DNFB), urushiol, 3-n-pentadecylcatechol (PDC), 4-ethoxymethylene-2-phenyloxazol-5-one (oxazolone)] and tolerizing compounds [2,4-dinitrothiocyanobenzene (DNTB), 5-methyl-3-n-pentadecyl-catechol (5-Me-PDC)] onto the earskin of non-sensitized Balb/c mice. In addition, we applied croton oil as a non-sensitizing, but stimulatory agent. Cytokine production was demonstrated by Northern blot hybridization of the total cellular RNA extracted from epidermal cells depleted by Langerhans cells and Thy 1+ dendritic cells using radiolabeled DNA probes encoding for the murine cytokines IL-1 alpha, -2, -3, -4, TNF alpha, IFN tau, GM-CSF and G-CSF. From all cytokines tested, TNF alpha and IL-1 alpha were markedly increased upon in vivo stimulation with contact sensitizers and also after application of croton oil. Both light and electron microscopic immunostaining with a polyclonal and monoclonal antibody demonstrated the presence of TNF alpha in the epidermis. This staining was most pronounced in KCs of the suprabasal epidermis upon application of contact sensitizers or croton oil, but not with tolerizing analogues. Using a functional assay significantly more TNF alpha was found in the supernatants of KCs treated in vitro with DNFB or LPS than with DNTB. GM-CSF was found in untreated epidermis as well as in stimulated cells. The results suggest that the sensitizing properties of contact sensitizers may partly be dependent on their ability to induce proinflammatory mediators. The induction and release of TNF alpha and IL-1 alpha in KCs by contact sensitizers may play an important role in the early response to immunogenic or inflammatory signals in vivo, whereby tolerance induction seems to be less dependent on these cytokines.

Animals↗
PubMed1992

Increased expression of ICAM-1, E-selectin, and VCAM-1 by cultured human endothelial cells upon exposure to haptens.

Contact allergens induce several accessory signals which promote the activation of antigen-specific T cells. One of these signals is the increased expression of adhesion molecules on antigen-presenting cells and endothelial cells. Epicutaneous application of non-toxic doses of 2,4-dinitrofluorobenzene (DNFB) onto the skin of non-sensitized individuals elicited progressive staining for ICAM-1 on dermal microvascular endothelial cells. To elucidate the question of whether contact allergens can act directly on endothelial cells to elevate their expression of surface structures that bind leukocytes, confluent monolayers of human umbilical vein endothelial cells were incubated with the contact allergens NiSO4, CoSO4 or DNFB. The ICAM-1, E-selectin and HLA-DR expression were quantified by immunofluorescence flow cytometric analysis. Furthermore VCAM-1, E-selectin and ICAM-1 transcription were demonstrated by Northern blot hybridization. Constitutive ICAM-1 expression on HUVEC increased similarly to that obtained after LPS (20 micrograms/ml) stimulation after 4 and 24 hours of incubation with 1 or 2 mM NiSO4 or CoSO4, respectively. Pulse-stimulation with 100 or 500 nM DNFB resulted in a modest but significant increase of ICAM-1-positive cells. E-selectin and VCAM-1 were not expressed on untreated HUVEC; 4 to 6 hours exposure to nickel sulfate and LPS resulted in a potent induction of E-selectin and VCAM-1 expression. DNFB and PMA had no significant influence on VCAM-1 expression. None of the tested contact allergens was capable of inducing HLA-DR expression on EC at 48 to 72 hours. Enhanced expression of adhesion molecules may be an important early unspecific mechanism for induction and elicitation of a contact dermatitis.

Cell Adhesion Molecules↗
PubMed1992

99mTc-HMPAO-SPECT with acetazolamide challenge to detect hemodynamic compromise in occlusive cerebrovascular disease.

BACKGROUND AND PURPOSE: Insufficiency of collateral supply may lead to low-flow infarcts in severe occlusive cerebrovascular disease. The aim of this study was to evaluate the feasibility of technetium-99m-labeled hexamethylpropyleneamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) to assess hemodynamic compromise in the anterior circulation. METHODS: Cerebral blood flow before and after 1 g acetazolamide was analyzed by 99mTc-HMPAO-SPECT in 21 symptomatic patients with documented extracranial obstructions. SPECT findings were correlated with the results of angiography, transcranial Doppler sonography, and computed tomographic scan. RESULTS: The acetazolamide-induced increase of cerebral blood flow could be reliably monitored by increase of cerebral 99mTc-HMPAO uptake, which varied between 11.4% and 47.6% in the less-affected hemisphere. Increment of hemispheric side-to-side asymmetry of tracer uptake after drug challenge revealed significant restriction of regional vasoreactivity in 11 patients. Agreement in assessing hemodynamic compromise was reached in 81% of patients with ophthalmic artery collaterals on angiography (p < 0.001), in 76% with low-flow infarcts on computed tomographic scan (p < 0.01), and in 91% with markedly reduced flow velocities on transcranial Doppler (p < 0.0001). One patient developed a low-flow infarct in the area predicted by SPECT during follow up. CONCLUSIONS: We conclude that 99mTc-HMPAO-SPECT with acetazolamide challenge is a useful method for assessment of the adequacy of hemispheric collateral pathways in patients with severe occlusive cerebrovascular disease.

Acetazolamide↗
PubMed1991

[Alcohol abusers in the psychiatric emergency departments in Copenhagen and Frederiksberg].

On the basis of a prospective random sample investigation of 611 alcohol-related visits to the four psychiatric emergency units of the City of Copenhagen, demographic variables, referral sources and dispositions of treatment are described. On every 10th day throughout 1985 all visits were registered. The distribution of all variables except age and sex deviate significantly from those of non-alcohol-related visits. Thus fewer alcoholics cohabit and more are divorced. 25% of the alcohol-related visits resulted in an overnight stay in the unit, while 10% resulted in admission to the psychiatric ward. For non-alcohol-related visits the proportions were the reverse.

Adult↗
PubMed1991

Biochemical properties of MHC class II molecules endogenously synthesized and expressed by mouse Langerhans cells.

The cell surface expression and biosynthesis of Langerhans cells (LC)-derived major histocompatibility complex (MHC) class II molecules from epidermal cells (EC) prepared freshly and cultured for up to 3 days was investigated. Based on the constitutive expression of MHC class II determinants by LC, a panning and magnetic bead selection procedure was employed, yielding 65% and 86% of I-A+ cells, respectively. Phenotypical and cytochemical examinations revealed that the two LC preparations were free of contaminating macrophages as well as B and T cells. Freshly prepared enriched LC were highly efficient in the stimulation of protein antigen-specific T cell clones, while LC purified from short-term cultured EC suspensions proved to be more efficient allogeneic stimulator cells than fresh LC. Comparative analysis of LC obtained from freshly prepared and from short-term-cultured EC preparations indicated an up-regulation of MHC class II determinants during short-term culture. Radioiodination analysis of LC selected by magnetic beads demonstrated prominent class II alpha and beta chain signals with only a minute fraction of invariant chains p35 and p45 being expressed at the cell surface. Unlike class II complexes derived from B cells, those from LC contained invariant chain fragment p20 in association with alpha/beta heterodimers at the plasma membrane. No qualitative differences between freshly isolated and 3-day cultured LC in cell surface expressed MHC class II components were detectable. Metabolic labeling with subsequent two-dimensional electrophoresis revealed distinct features of LC-derived MHC class II molecules with a high proportion of invariant chains in particular gamma and p40 and their extensive sialylation. While fresh and 1-day cultured LC exhibited appreciable levels of newly synthesized class II molecules, a dramatic down-regulation in class II and invariant chain synthesis was measured after 3 days of continuous in vitro culture.

Animals↗
PubMed1991

[Radiotherapy of solitary and multiple eosinophilic granulomas of bone (stage I)].

Between 1957 and 1990 15 patients with solitary (stage Ia by Greenberger) and 2 patients with multiple (stage Ib) eosinophilic granuloma of the bone were treated by radiotherapy in 18 locations after previous surgery. The doses applied varied from 6 Gy to 42 Gy (median for patients under 18 years: 8 Gy, for patients over 18 years: 30 Gy). Median follow-up was 9 years (range, 0.3-33 years). Local control rate and survival were 100%. Three patients with granuloma developed a second granuloma within 13 years after primary diagnosis (two bone manifestations, one cutaneous manifestation). Long-term follow-up of patients with solitary eosinophilic granuloma is necessary.

Adolescent↗
PubMed1991

[Eosinophilic cellulitis--clinical and histological aspects].

Eosinophilic cellulitis (Wells' syndrome) is a rare skin disease whose aetiology is still unknown. The onset is acute, and different disease stages may exist simultaneously during the course. Histological examination shows flame figures as a characteristic, but not pathognomonic, feature. In later stages the infiltrate adopts granulomatous characteristics. Malignant haematological disorders, which frequently occur with this disease, should be excluded.

Cellulitis↗
PubMed1990

Scintigraphic evaluation of tumor regression during preoperative chemotherapy of osteosarcoma. Correlation of 99mTc-methylene diphosphonate parametric imaging with surgical histopathology.

The effect of preoperative chemotherapy (PCT) on the uptake of 99mTc-labeled diphosphonates into tumor bone was quantitatively assessed from serial scan studies of 30 osteosarcomas and correlated with the histomorphological changes determined from the surgical specimens. The parametric images of the tumor blood pool and labeled methylene diphosphonate (99mTc-MDP) plasma clearance by the tumor bone enabled a sensitive distinction to be made preoperatively between a good (greater than 90% tumor cell destruction) and a poor (less than 90% tumor cell destruction) tumor response. Overall accuracy in presurgical prediction of tumor regression was found to be 88% and 96% for the blood pool and 99mTc-MDP clearance measurements, respectively (P less than or equal to 0.0004). In addition, it proved possible to localize resisting areas of viable tumor up to 1.0 cm in diameter. Even at the half-way stage of PCT, a poor response could be reliably predicted (overall accuracy 91% and 100%, respectively; P less than or equal to 0.011). Therefore, 99mTc-MDP parametric imaging is a highly sensitive and specific modality for an objective and accurate assessment of tumor regression during PCT of osteosarcoma.

Adolescent↗
PubMed1990

Immunologic effects of interferon.

Interferons can be defined as a family of induced proteins sharing the capacity to exert pleiotropic effects on cell functions and to render cells resistant to virus infection. They are activating genes coding for a number of enzymes, most of which have not yet been characterized, and also by enhancing the synthesis of cell surface components. This enables interferons to modulate the immune response at different levels. This article will focus on the effects of interferon on antigen presentation, regulation of the immune response, activation of macrophage functions, and on its role in the pathogenesis of some diseases.

Animals↗
PubMed1990

Antigens of the major histocompatibility complex in patients with chronic discoid lupus erythematosus.

The frequencies of the major histocompatibility complex class I, class II and class III antigens were determined in 130 patients (88 women and 42 men) with chronic discoid lupus erythematosus, and compared with those of 764 healthy controls. A significant increase in HLA-B7 (38.0% in the patients vs. 25.8% in the control group), HLA-B8 (29.5% vs. 17.4%), HLA-Cw7 (58.9% vs. 26.1%), HLA-DR2 (46.9% vs. 29.7%), HLA-DR3 (32.0% vs. 19.4%), HLA-DQw1 (76.6% vs. 60.5%), and a decrease in HLA-A2 (41.9% vs. 55.7%) was found. The calculated relative risk values for the respective antigens markedly increased when two or more antigens were present in one patient, with a maximum relative risk value of 7.4 for the combinations of HLA-Cw7, DR3, DQw1 and HLA-B7, Cw7 and DR3, which were found in 17.2% of the patients and in only 2.3% of the controls.

Chronic Disease↗
PubMed1990

Childhood antecedents of antisocial behavior: parental alcoholism and physical abusiveness.

Hierarchical logistic regression was used to assess the independent and interactive effects of paternal alcoholism and physical child abuse on antisocial behavior in young adult men. Men with alcoholic fathers (N = 131) did not report or exhibit more antisocial behavior than comparison subjects (N = 70). Men with physical abuse histories, however, reported more aggressive and antisocial behaviors during a clinical interview and were rated by a clinical interviewer as more likely to act out aggression. Arrest records did not distinguish the groups. There was no evidence that paternal alcoholism and childhood victimization interacted to increase the risk of antisocial behavior.

Acting Out↗
PubMed1990

Fat-storing hamartoma of dermal dendrocytes. Clinical, histologic, and ultrastructural study.

A 30-year-old man is described who since birth had a peculiar symmetrical red-brown micronodular cutaneous plaque. Within the slightly raised plaque, small firm nodules were palpable. Histologic examination revealed phagocytic cells with the appearance of histiocytes between the collagen fibers of the reticular dermis. Immunohistochemical and electron microscopic examination confirmed that the cells of the plaque were dermal dendrocytes with phagocytic activities. The existence of the lesion since birth, the phagocytosis of lipid droplets by the cells, and the lack of associated metabolic disturbances suggest a fat-storing hamartoma of dermal dendrocytes that does not correspond to a known fat-storing or fat-producing tumor.

Adult↗