Rita Káposzta

A Functional Soluble Form of the Murine Mannose Receptor Is Produced by Macrophages in Vitro and Is Present in Mouse Serum

A soluble form of the mannose receptor (sMR) has been found in conditioned medium of primary macrophages in vitro and in mouse serum. sMR was released as a single species, had a smaller size than the cell-associated form, and accumulated in macrophage-conditioned medium, in a cytokine-regulated manner, to levels comparable with those found for cell-associated mannose receptor. Pulse-chase experiments showed that sMR production in culture occurred by constitutive cleavage of pre-existing full-length protein. A binding assay was developed to determine the sugar specificity of sMR and its ability to interact with pathogens and particulate antigens (i.e. Candida albicans and zymosan). Protease inhibitor studies suggested that sMR was produced by cleavage of an intact mannose receptor by a matrix metalloprotease or ADAM metalloprotease. A role for sMR in the immune response is proposed based on its binding properties, regulation by cytokines, and the previous discovery of putative ligands for the cysteine-rich domain of the mannose receptor in lymph nodes and spleen.

Survival of group B streptococcus type III in mononuclear phagocytes: differential regulation of bacterial killing in cord macrophages by human recombinant gamma interferon and granulocyte-macrophage colony-stimulating factor.

ABSTRACT Phagocytic and killing capacities of resident and cytokine-activated human macrophages against group BStreptococcus (GBS) type III were studied. Evidence is presented that monocyte-derived macrophages from cord and adults ingest serum-opsonized GBS but that killing of bacteria was negligible in resident cells. Treatment of adult macrophages with recombinant human gamma interferon (rhIFN-γ; 100 U/ml) or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 200 U/ml) resulted in significant increases of killing of GBS (P< 0.01 for each). The killing capacity of cord macrophages treated with rhGM-CSF was also enhanced compared to that of untreated cells (P < 0.01). However, treatment with rhIFN-γ resulted in only a moderate increase in the capacity of cord macrophages to kill GBS (P > 0.1). These results mirrored the effect of rhIFN-γ on candidacidal capacities of cord and adult macrophages, reported earlier from our laboratory. These data indicate differential modulation of neonatal macrophages by rhGM-CSF and rhIFN-γ. We suggest that administration of rhGM-CSF to neonates with invasive GBS disease may enhance host resistance to these bacteria.

Early Corneal Cellular and Nerve Fiber Pathology in Young Patients With Type 1 Diabetes Mellitus Identified Using Corneal Confocal Microscopy

PURPOSE The aim of this study was to quantify epithelial, stromal, and endothelial cell density, and subbasal nerve morphology in young patients with type 1 diabetes mellitus with and without diabetic retinopathy. METHODS A total of 28 young patients (mean age, 22.86 ± 9.05 years) with type 1 diabetes, with (n = 18) and without (n = 10) retinopathy, and 17 age-matched healthy control subjects (mean age, 26.53 ± 2.43 years) underwent corneal confocal microscopy (CCM). RESULTS We found significantly lower epithelial (P < 0.0001) and endothelial (P = 0.001) cell densities and higher keratocyte cell density (P = 0.024) in patients with type 1 diabetes compared to controls. Significantly lower corneal nerve fiber density (P = 0.004), nerve branch density (P = 0.004), total nerve branch density (P = 0.04), and nerve fiber length (P = 0.001), and greater nerve fiber width (P = 0.04) were observed in patients with type 1 diabetes compared to control subjects. Significantly lower epithelial (P < 0.001) and endothelial (P = 0.02) cell densities, nerve branch density (P = 0.02), and nerve fiber length (P = 0.04), and significantly higher keratocyte cell density (P = 0.02) were found in patients with type 1 diabetes without retinopathy compared to control subjects. CONCLUSIONS Corneal confocal microscopy identifies corneal cellular and small nerve fiber pathology in young patients with type 1 diabetes without retinopathy, which increases in severity in those with retinopathy. Corneal confocal microscopy appears to have considerable use as an imaging biomarker for early subclinical pathology in young patients with type 1 diabetes mellitus.

Chronic neutropenia and defect in superoxide generation of granulocytes in two patients: enhancement of bactericidal capacity and respiratory burst activity by treatment with recombinant human granulocyte colony-stimulating factor.

ABSTRACT: We have identified two unrelated girls with chronic neutropenia [absolute neutrophil counts (ANC) 10–870 and 10–940/μL in patients 1 and 2, respectively] and severe defect in superoxide anion generation by granulocytes. Formyl-methionyl-leucyl-phenylalanine-induced superoxide release was 1.2 ± 0.9 and 1.9 ± 1.9% (mean ± SEM, n = 3) of normal controls‘, mean value in patients 1 and 2, respectively. However, granulocytes from both patients released a normal amount of superoxide upon stimulation with phorbol myristate acetate. Patient 2 exhibited characteristic features of Duane syndrome, a rare disorder of eye movement. Treatment of the patients with recombinant granulocyte colony-stimulating factor led to significant clinical improvements and reduction of infectious complications and to increases in the ANC, to 400–2100/μL in patient 1 and to 500–3000/μL in patient 2. Treatment with 5 μg/kg/d resulted in increased intracellular killing of opsonized Staphylococcus aureus by granulocytes and an enhancement of superoxide release upon stimulation with formyl-methionyl-leucyl-phenylalanine in both patients up to 11.1 ± 6.0 and 13.5 ± 7.0% (mean ± SEM, n = 5) of normal controls’, mean value in patient 1 and patient 2, respectively. These data suggested that recombinant human granulocyte colony-stimulating factor treatment enhanced resistance to bacterial infection by stimulation of superoxide generation and increasing the bactericidal capacity of peripheral blood granulocytes.

Alterations of carbohydrate and lipoprotein metabolism in childhood obesity--impact of insulin resistance and acanthosis nigricans

AIM To study the prevalence of alterations of glucose and lipoprotein metabolism and the impact of acanthosis nigricans (AN) in childhood obesity. PATIENTS AND METHODS 113 obese children, 57 with simple obesity (SO) and 58 with obesity and AN (OAN). Oral glucose tolerance test was performed, serum glucose, insulin and lipoprotein parameters were determined, and insulin resistance/sensitivity indices were calculated. RESULTS Insulin resistance, basal and reactive hyperinsulinemia, impaired glucose tolerance (IGT) and dyslipidemia were found to be frequent conditions in children with OS as well as OAN. Reactive insulinemia was more pronounced in OAN than in SO, and insulin resistance was more frequent when AN was more prominent. Triglycerides were higher and HDL-C was lower, and atherogenic dyslipidemia was more frequent in OAN compared to SO. CONCLUSION Children with obesity form a risk population. AN is a factor which can be used in metabolic risk factor clustering estimation in childhood obesity.

Cellular mechanisms of phagocytosis of Candida by murine macrophages

Publisher Summary The uptake of Candida yeasts has the characteristics of phagocytosis, requires intact actin filaments, and a microtubular network. Phagocytic uptake of yeasts by peritoneal membranous organelle (MO) is relatively rapid and involves recruitment of late endocytic/lysosomal organelles. Vacuolar fusion in MO promotes the germ tube formation of Candida, although sprouting is generally suppressed in internalized yeasts. Germ tubes are more invasive, can escape from phagolysosomes, and penetrate intact MO, even when phagocytosis of yeasts is blocked by different inhibitors. Invading germ tubes also recruit Lamp+ organelles, which requires active endoplasmic reticulum Ca2+-ATP-ase; however, an intact actin-cytoskeleton is not essential. The inhibition of the lysosomal H + -ATP-ase and of associated lysosomal fusion reduces germ tube formation of Candida within the phagolysosomes. These data suggest that rapid recruitment of late endocytic/lysosomal organelles and vacuolar fusion might be part of the survival strategy and pathogenicity of both forms of C. albicans .

Endocrine and anatomical findings in a case of Solitary Median Maxillary Central Incisor Syndrome

Solitary Median Maxillary Central Incisor Syndrome (SMMCI) is a rare malformation syndrome consisting of multiple, mainly midline defects. Some authors suggest that it is a mild manifestation of the wide spectrum of holoprosencephaly, others classify it rather as a distinct entity. Authors report a case of SMMCI presenting with growth retardation, mild intellectual disability and absence of puberty. Cytogenetic and molecular cytogenetic investigations could identify no abnormalities. The presence of a single maxillary incisor called for further investigations to clarify hidden anomalies, these were empty sella, panhypopituitarism, hypothyroidism, and hypoplasia of the inner genitals. Based on the above findings, growth hormone, estrogen, and L-thyroxine substitution was introduced, which resulted in satisfactory longitudinal growth and onset of sexual maturation. We suggest genetic counselling and if needed, invasive investigations in female patients with short stature and absent/delayed puberty, with or without sex chromosomal anomalies, as the adequate therapy and even the quality of life of patient depends largely on the knowledge of their anatomical and endocrine status.

The Hungarian version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR)

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Hungarian language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach’s alpha, interscale correlations, test–retest reliability, and construct validity (convergent and discriminant validity). A total of 206 JIA patients (3.9% systemic, 41.3% oligoarticular, 28.2% RF-negative polyarthritis, 26.6% other categories) and 90 healthy children, were enrolled in two centres. The JAMAR components discriminated healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Hungarian version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Acquisition and use of myeloperoxidase in the fungicidal activity of macrophages

Myeloperoxidase (MPO), a basic hemoprotein enzyme present in the primary granules of neutrophils and monocytes plays a critical role in the fungicidal activity of these cells [1, 2]. In vitro phagocytes genetically deficient in MPO fail to kill Candida albicans and patients with hereditary MPO deficiency have an increased susceptibility to invasive C. albicans infections [3].