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D Roos

Publications and source records attributed to D Roos.

357 records · Page 20Linked to original sources
PubMedDate not supplied

Hematologically important mutations: leukocyte adhesion deficiency.

Leukocyte adhesion deficiency (LAD) is an immunodeficiency caused by defects in the adhesion of leukocytes (especially neutrophils) to the blood vessel wall. As a result, patients with LAD suffer from severe bacterial infections and impaired wound healing. In LAD-I, mutations are found in INTG2, the gene that encodes the beta subunit of the beta(2) integrins. In the rare LAD-II disease, the fucosylation of selectin ligands is disturbed, caused by mutations in the gene for a GDP-fucose transporter of the Golgi. This article summarizes all known patient mutations and polymorphisms in these genes.

CD18 Antigens↗
PubMedDate not supplied

Visceral leishmaniasis and other severe infections in an adult patient with p47-phox-deficient chronic granulomatous disease.

We report a rare case of a male patient without known immunodeficiency consecutively diagnosed with visceral leishmaniasis, brain abscess and cavitating pneumonia in the 3rd decade of life. Chronic granulomatous disease (CGD) was diagnosed by a nitroblue tetrazolium test. A p47-phox mutation of the NADPH oxidase of the leukocytes was suspected by immunoblotting and confirmed by DNA analysis. The patient was homozygous for this mutation while his mother and sister were heterozygous asymptomatic carriers. After the CGD diagnosis the patient started a chronic prophylactic regimen with subcutaneous interferon-gamma (0.05 mg/m2 of body surface/three times a week), and oral trimethoprim-sulfamethoxazole and itraconazole (both at 5 mg/kg/day) with no subsequent infections after 12 months of follow-up.

Adult↗
PubMedDate not supplied

Complementation in monocyte hybrids revealing genetic heterogeneity in chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a rare syndrome, found predominantly in male children and characterized by life-threatening, recurrent infections. The superoxide (O2-)/hydrogen peroxide (H2O2) generating system in the granulocytes and monocytes of CGD patients is completely defective. Furthermore, a novel type of cytochrome b, detected by the optical spectrum of phagocytes from healthy subjects, is lacking in those of most male CGD patients. In female CGD patients, the cytochrome b is present, but cannot, as in normal cells, be reduced on metabolic stimulation of the phagocytes in anaerobic conditions. Here, to demonstrate the importance of cytochrome b in this system and to investigate the genetic background of the various forms of CGD, we have hybridized monocytes from a cytochrome b negative, X-linked male CGD patient with monocytes from a cytochrome b positive, male CGD patient with unknown genetic background. Monocytes were used because they are the only blood phagocytes that show an active protein synthesis, whereas fibroblasts or lymphocytes do not express the O2-/H2O2 generating system. The heterologous hybrids were positive in the nitroblue tetrazolium (NBT) slide test, indicating the complementation of the O2-/H2O2 generating system, whereas the homologous hybrids remained negative, as did the non-fused cells of these patients. We thus conclude that cytochrome b is part of the O2-/H2O2 generating system and that somatic cell hybridization experiments with monocytes provide a means of studying the genetic background of CGD patients. We believe this to be the first report of genetic complementation by somatic cell hybridization experiments using monocytes instead of fibroblasts.

Chromosomes↗
PubMedDate not supplied

Medium-chain, triglyceride-containing lipid emulsions increase human neutrophil beta2 integrin expression, adhesion, and degranulation.

BACKGROUND: To test the hypothesis that lipid emulsions with different triglyceride structures have distinct immunomodulatory properties, we analyzed human neutrophil adhesion and degranulation after lipid incubation. METHODS: Neutrophils, isolated from the blood of 10 healthy volunteers, were incubated in medium or physiologic (2.5 mmol/L) emulsions containing long-chain (LCT), medium-chain (MCT), mixed LCT/MCT, or structured (SL) triglycerides. Expression of adhesion molecules and degranulation markers was evaluated by flow cytometry. Also, functional adhesion was investigated by means of a flow cytometric assay using fluorescent beads coated with the integrin ligand intercellular adhesion molecule (ICAM)-1. RESULTS: Although LCT and SL had no effect, LCT/MCT significantly increased expression of the beta2 integrins lymphocyte-function-associated antigen 1 (+18%), macrophage antigen 1 (+387%), p150,95 (+82%), and (alphaDbeta2 (+230%). Degranulation marker expression for azurophilic (CD63, +210%) and specific granules (CD66b, +370%) also significantly increased, whereas L-selectin (CD62L, -70%) decreased. The effects of LCT/MCT were mimicked by the MCT emulsion. ICAM-1 adhesion (% beads bound) was increased by LCT/MCT (34% +/- 4%), whereas LCT (19% +/-3%) and SL (20% +/- 2%) had no effect compared with medium (17% +/- 3%). CONCLUSIONS: LCT/MCT and MCT, contrary to LCT and SL emulsions, increased neutrophil beta2 integrin expression, adhesion, and degranulation. Apart from other emulsion constituents, triglyceride chain length might therefore be a key feature in the interaction of lipid emulsions and the phagocyte immune system.

Adult↗
PubMedDate not supplied

Design and test of microwave interstitial applicators with improved longitudinal heating pattern.

A microwave applicator for interstitial hyperthermia was designed for use in conjunction with interstitial radiation therapy. Measurements were performed in phantom material and in the hind legs of anaesthetized pigs. In both studies two applicators were inserted in parallel at a distance of 2 cm and to a depth of 6 cm. The temperature distribution produced by two conventional applicators were compared with the temperature distribution produced by two applicators of the new design. Improvement of the heating pattern was found in both phantom and animal studies; the heating pattern produced by the new applicators was shifted towards the tip. This may be of clinical importance as heating can be achieved without applicator penetration through tumour tissue into normal tissue.

Animals↗
PubMedDate not supplied

A new microwave applicator with integrated cooling system for intracavitary hyperthermia of vaginal carcinoma.

An improved design of a previously described intracavitary microwave hyperthermia applicator is presented. The applicator consists of a coaxial choke antenna designed to be positioned into a perspex obturator. The antenna can be fitted in the obturator in three defined positions depending on the specific clinical situation: the selected median, paramedian or lateral position can each provide differently directed heating patterns. This feature combined with the additional axial variability of the antenna position within the obturator can lead to a highly targeted heating of tumours and a reduced risk of unwanted heating of normal tissues. Various phantom studies were conducted using both liquid and solid phantoms. The saline phantom was used to check the typical action of the choke of the antenna where it was found that the antenna choke is efficiently working resulting in a heating pattern which is dependent of the insertion depth of the antenna. The solid phantom was used to measure the typical specific absorption rate (SAR) distribution of each antenna/obturator configuration.

Carcinoma↗
PubMedDate not supplied

Defects in the oxidative killing of microorganisms by phagocytic leukocytes.

One of the most important mechanisms of phagocytic killing of ingested microorganisms by leukocytes is the generation of toxic oxygen products. During phagocytosis, neutrophils, as well as monocytes and macrophages, display a strongly increased cell respiration. Quantitatively the most important product of this reaction is hydrogen peroxide. Superoxide is also generated in large amounts, probably as an intermediate in the formation of hydrogen peroxide. Indications exist that singlet oxygen and hydroxyl radicals are also formed in this process. Some of these oxygen products have microbicidal properties by themselves. The effect of hydrogen peroxide is greatly enhanced by the enzyme myeloperoxidase. Several dysfunctions of this sytem are known. In chronic granulomatous disease the enzyme system that produces superoxide is not operative. Thus, no superoxide or hydrogen peroxide is generated, leading to a severely decreased bacterial killing capacity. The exact molecular defects in the X-linked and the autosomal form are as yet undefined. Two variants are also known: lipochrome histiocytosis, with different clinical and histological manifestations, and a 'triggering defect' where only strongly opsonized particles trigger the respiratory burst. Myeloperoxidase deficiency leads to slightly decreased killing capacity, especially for yeasts. In glucose-6-phosphate dehydrogenase deficiency no oxygen radicals or hydrogen peroxide are produced because no equivalents for oxygen reduction can be generated in the hexose-monophosphate shunt. Deficiencies in the glutathione redox system also result in impaired phagocyte function, probably because the cells have to be protected against their own toxic oxygen products.

Blood Bactericidal Activity↗
PubMedDate not supplied

Phagocytosis and degradation of DNA-antiDNA complexes by human phagocytes. Influence of rheumatoid factors.

We studied the influence of sera that contain rheumatoid factor (RF) or purified RF of the IgM and IgG class on the size and the processing (phagocytosis plus degradation) of DNA-antiDNA complexes by human phagocytes. Low concentrations of fresh serum with IgM RF increased the size of small DNA-antiDNA complexes, but at higher concentrations prevented formation of large complexes. The latter effect resulted from interaction of the complexes with complement. By increasing the size of the complexes, purified IgM RF enhances the processing by monocytes and neutrophils of small DNA-antiDNA complexes, prepared at antigen excess. IgM RF inhibited the processing of large DNA-antiDNA complexes, probably by blocking the Fc parts of the IgG antiDNA. IgM RF had a biphasic influence on the processing of small DNA-antiDNA complexes, prepared at antibody excess: an increasing effect due to an increase in size of the complexes and, at higher concentrations of RF, a decreasing effect due to the covering of Fc parts. The inhibiting effect on complex processing was abolished by opsonization with C3. Purified IgG RF increased the size of small DNA-antiDNA complexes, and in parallel the processing of these complexes. IgG RF hardly affected the processing of large DNA-antiDNA complexes.

Antigen-Antibody Complex↗
PubMedDate not supplied

[An opsonin-independent strain of Staphylococcus epidermidis].

Human neutrophils, subjected to stimulation under different conditions (phorbol myristate acetate, opsonized zymosan, formylmethionyl-leucinephenylalanine, nonopsonized staphylococci), produced a factor (denoted as clumping factor, or CF) with a capacity for highly selective clumping and opsonization of staphylococci. Out of 68 strains of different species of staphylococci, only a single strains (S.epidermidis) was sensitive of CF. CF negative staphylococci were capable of inducing the release of CF by neutrophils, but were not bound by this factor. Extracts, obtained by the mechanical destruction of neutrophils (sonication, repeated freezing and thawing), had no clumping activity. CF had a mol. wt. exceeding 100 kD, was positively charged and disintegrated at 100 degrees C. The capacity of S.epidermidis 178 M for binding CF completely disappeared after the treatment of bacteria with pronase and partially disappeared after boiling and treatment with trypsin and periodate. Neuraminidase and heating at 80 degrees C produced no effect. These data are the first demonstration of highly selective (strain-specific) interaction between secretory products of neutrophils and bacteria.

Antibodies, Bacterial↗