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Clinical Neuroscience

JANUARY 30, 2006

[THE SIGNIFICANCE OF CHLAMYDIA PNEUMONIAE IN SELECTED NEUROLOGIC DISORDERS]

HORVÁTH Zoltán, VÉCSEI László

[Chlamydia pneumoniae has recently been implicated in the pathogenesis of several neurological diseases. As an intracellular parasite with its unusual life cycle it is able to circumvent the immune system and to persist in the organism. It has the ability to modify the function of the infected cell and supposedly induce autoimmune reactions. These properties can make it pathogenic in several chronic neurological diseases including multiple sclerosis, atherosclerosis, stroke, Alzheimer dementia and giant cell arteriitis. The evaluation of the available, often contradictory, data that are based on various different methods is not easy. The importance of the issue is enhanced by the potential need for antibiotic treatment.]

Lege Artis Medicinae

OCTOBER 20, 2010

[Postmenopausal changes of immune system-related genes expression in human bone tissue]

BALLA Bernadett, KÓSA P. János, KISS János, PODANI János, TAKÁCS István, LAZÁRY Áron, BÁCSI Krisztián, NAGY Zoltán Zsolt, SPEER Gábor, LAKATOS Péter

[INTRODUCTION - The molecular and cellular interactions between the immune system and bone tissue have been established. Sex hormone deficiency at the time of menopause has multifunctional role by influencing growth, differentiation and metabolism of the skeletal and the immune system. We have used non-parametric and multidimensional expression pattern analyses to determine significantly changed mRNA profile of immune system-associated genes in postmenopausal (POST) and premenopausal (PRE) non-osteoporotic bone. MATERIALS AND METHODS - Ten bone tissue samples from POST patients and six bone tissue samples from PRE women were examined in our study. The transcription differences of selected 50 genes were analyzed in Taqman probe-based quantitative real-time RT-PCR system. RESULTS - Mann-Whitney test indicated significantly down-regulated transcription activity of 3 genes (CD14, HLA-A, ITGAM/CD11b) and upregulated gene expression of 6 genes (C3, CD86, IL-10, IL-6, TGFB3, TNFSF11/RANKL) in POST bone. According to the canonical variates analysis results, the groups of postmenopausal and premenopausal women are separable by genes coding for cytokines, co-stimulators and cell surface receptors affected in antigen presentation and T cell stimulation which have high discriminatory power. CONCLUSIONS - Based on a complex gene expression patterns in human bone cells, we could distinguish POST and PRE states from an immunological aspect. Our data might provide further insight into the changes of the intersystem crosstalk between immune and skeletal system, as well as local immune response in the altered microenvironment of POST bone.]

Lege Artis Medicinae

OCTOBER 20, 2005

[THE INFLUENCE OF IMMUNOGENOMIC FACTORS ON HIV-INFECTION]

FÜST György

[Authors discuss data published in the last 2-3 years indicating that besides the characteristics of the virus itself, the natural course of HIV disease is also regulated by genetic factors from the very onset till the end. Susceptibility for HIV infection of the carriers of a non-expressing mutant allele (CCR5Δ32) of one of the main coreceptors of HIV is markedly lower than that of the non-carriers. HLA-concordancy, that is few differences in the HLA alleles between the infected and noninfected partners, increases the chance of the HIVtransmittal. On the other hand, carriage of some HLA genotype e.g. that of the HLA A2/6802 supertype may significantly decrease the risk of the sexually transmitted HIV infection or that of the HIV infection from the mother to child. The rate of progression of the HIV disease which may vary in broad range from the median value of 10 years is also dependent on genetic factors. Progression is lower than the average in the carriers of the CCR5Δ32, HLA-B*27 and HLAB* 57 alleles while it is significantly more rapid in carriers of the HLA-B*35.1 allele. Recent data on the regulation by genetic factors of some sideeffects and the efficacy of combined antiretroviral treatment indicate that in the near future individual treatment may be used on the basis of the genetic background of the patients.]

Lege Artis Medicinae

JANUARY 20, 2011

[Effective adalimumab treatment of a steroid-dependent Crohns’ disease patient suffering from general, abdominal and joint symptoms of multiple etiology]

JUHÁSZ Márk, TÓTH Zsuzsanna, MIHELLER Pál, SZŰTS Ildikó, GAÁL Ramóna, PÁPAY Judit, PREGUN István, TULASSAY Zsolt, RÁCZ Károly, MŰZES Györgyi

[The 69-year-old male patient had been suffering from periodically relapsing rheumatological symptoms involving variable localisations (knee, ankle, MTP, sternoclavicular and hip joint) since 1964. On the basis of his joint symptoms, load-independent lower back pain, sacroileitis, recurrent iridocyclitis, urethroprostatitis and oral aphtous lesions, Reiter disease was diagnosed in 2000. The patient had Lyme-disease (confirmed Borrelia burgdorferi seropositivity) with peripheral facial paresis in 2003. The patients joint problems relapsed in 2006, accompanied by diarrhoea and fever, independent of any infecions. The possibility of IBD could not be confirmed either by macroscopic examination using colonoscopy or hystology. The patient was admitted to our department in March 2008 for the first time, presenting again with joint pain and disability of gait, 7-8 bowel movements a day, and fever. Taken together the clinical symptoms, the typical radiological findings and HLA-B27 positivity, Bechterew disease was diagnosed. Colonoscopy performed because of diarrhea revealed multiple segmental aphtoid lesions and irregular ulcers, suggesting Crohn disease that was confirmed by histology (cryptal abscess formation and microgranulomas). Sulfasalazin, 5-ASA, and other NSAIDs applied to treat rheumatological symptoms could not eliminate either the gastrointestinal or the rheumatological symptoms of the patient, which necessitated regular steroid therapy. Because of the patient’s steroid dependency, and considering his rheumatological symptoms, in June 2008 he was treated with adalimumab (ADA) induction therapy (80-40-40 mg s.c.). In two weeks, his gastrointestinal as well as extraintestinal symptoms substantially improved, and completely diminished through the course of maintenance ADA therapy (40mg weekly). The patient is still asymptomatic and is excercising (jogging) regularly.]

Hungarian Immunology

OCTOBER 10, 2005

[Extensive flow cytometric characterization of plasmocytoid dendritic cell leukemia cells]

GOPCSA László, KORMOS Luca, BÁNYAI Anikó, TAMÁSKA Júlia, MATOLCSY András, GOGOLÁK Péter, RAJNAVÖLGYI Éva, PÁLÓCZI Katalin

[INTRODUCTION - Accumulating evidences suggest that non-T, non-B cell CD4+/CD56+ neoplasms with lymphoblastic morphology include clinically and immunophenotypically diverse entities. Although their cells of origin or classification are still controversial several entities clearly represent a distinct type of neoplasms that are clinically aggressive. CASE REPORT - In this work we present the immunophenotypic and genotypic features of bone marrow, peripheral blood, lymph node and skin lymphocytes from a patient diagnosed as plasmacytoid dendritic cell leukemia involving the skin, bone marrow, peripheral blood, lymph nodes, liver and spleen. For determination of immunophenotypic characteristics of malignant plasmacytoid dendritic cells 73 monoclonal antibodies detecting lineage markers, chemokine receptors, cytokine receptors, activation and co-stimulatory molecules were used. The malignant cells proved to express CD4+, CD56+ lineage negative leukemia phenotype characteristically positive for CD36, CD38, CD40, CD45, CD45RA, CD68, CD123, CD184, HLA-DR, BDCA2 and granzyme-B corresponding to the preplasmacitoid dendritic cell developmental stage. CONCLUSION - The presence of CD11a/CD18, CD84, CD91, CD95, αvβ5, CDw197 and the absence of CD52 and CD133 in this case can be regarded as additional features of malignant cells.]

Lege Artis Medicinae

JULY 20, 2004

[THE GENETICS OF DIABETES MELLITUS]

KORÁNYI LÁSZLÓ, PÁNCZÉL Pál

[The number of diabetic patients will be doubled in the coming decades reaching 300 million for year 2025. The number of type 1 diabetics will also be increased but the majority of it will result from the increased number of type 2 diabetics. All types of diabetes are the consequence of a combination of genetic susceptibility and environmental factors, meaning that the prevention of diabetes epidemic cannot be done without the clarification of the genetic background. Significant progression has happened in the discovery of the genetic background of type 1 diabetes mellitus. It was helped by the etiologic classification of the disease: with the new classification the patient groups became more homogeneous. The HLA system is responsible for about 50-70% of the genetic risk while the effects of other genetic factors contribute 1-2% of the genetic susceptibility, respectively. Presently 25 gene regions are known as the different genetic factors of type 1 diabetes mellitus. Regarding the HLA system, the genes and pathomechanism causing the disease are not known. The classification of diabetes mellitus can be based on the HLA type while the predictability of type 1 diabetes mellitus is helped by the HLA type and the INS-VNTR. Much less is known about the genetic background of the polygenic type 2 diabetes mellitus. Its manifestation is now happening at younger age before. The best-fit genetic model consists of only a few genes with moderate effect superimposed on a polygenic background. Several „candidate” genes participating in the impaired insulin secretion and insulin action have already been investigated as the genes responsible for type 2 diabetes. These data showed the specificity in the population and most showed mild or modest association with the disease. Genomewide scans have resulted a number of significant diabetes susceptibility genes specific for a variety of populations, but these investigations have only resulted in the isolation of one gene (calpain 10) that is thought to contribute to type 2 diabetes. Most recent genomewide scans found loci on chromosome 20 in two different populations with significant segregation of type 2 diabetes. These loci are near to the region harboring the transcription factor hepatocyte nuclear factor genes. The transcription regulator HNF family is responsible for the regulation of the expression of several genes participating in the function of liver and pancreatic islet becoming a strong candidate for being a diabetes gene.]

Hungarian Immunology

MAY 10, 2004

[Immunology of Felty’s syndrome]

BÁLINT Géza, BÁLINT Péter

[Felty’s syndrome can be regarded as “super-rheumatoid” disease. Immungenetically the syndrome is much more homogenous, than rheumatoid arthritis. HLA-DRB1*0401 antigen is present in 83% of the patients. Felty’s syndrome develops usually after a longer course of rheumatoid arthritis, in 1% of rheumatoid patients. Rheumatoid arthritis patients with long lasting unexplained neutropenia can be diagnosed having Felty’s syndrome, even without detectable splenomegaly. On the contrary, rheumatoid arthritis with splenomegaly, but without present or previous neutropenia with unexplained origin cannot be regarded as having Felty’s syndrome. Inspite of the fact, that the arthritis of Felty’s syndrome can be inactive, because of the neutropenia and increased risk of recurrent infections, the patients should be kept under tight supervision, and should be properly treated, if required. Immunologically Felty’s syndrome is characterized by rheumatoid factor positivity in 95-100%, ANA positivity in 50-100%, antihistone positivity in 63-83%. Antibodies against dsDNA rarely, but against ssDNA frequently occur. No anti Sm and interestingly no anti Ro and anti La antibodies can be detected inspite of the high incidence of associated Sjögren’s syndrome. Immunoglobulin levels are higher and complement levels are lower, than in rheumatoid arthritis. Circulating immuncomplex level is usually high. Non-specific antineutrophil anticitoplasmatic antibodies can be found in high percentage. The neutropenia of Felty’s syndrome can be either caused by increased IgG neutrophilic binding activity or by inhibition of the granulocytes colony growing in the bone marrow, by peripheral blood mononuclear cells. Expansion of large granular lymphocytes can be seen in 30-40% of patients with Felty’s syndrome. Large granular lymphocyte syndrome is not rarely associated with rheumatoid arthritis. The neutrophil account is normal or elevated in this syndrome, but splenomegaly occurs. These cases are called as pseudo Felty’s syndrome. The patients with Felty's syndrome suffering from recurrent infections required treatment even if the arthritis is inactive. Methotrexate treatment should be started first, if this treatment fails, other disease modifying drugs or colony stimulating factor can be given. There is no experience with other biological treatments. In treatment of resistant cases splenectomy is indicated. Non-steroid anti-inflammatory drugs should be better avoided.]

Hungarian Immunology

MAY 10, 2004

[Investigation of activated T-cells by non-Hodgkin’s lymphoma patients]

VÁRÓCZY László, GERGELY Lajos, ALEKSZA Magdolna, MILTÉNYI Zsófia, ILLÉS Árpád

[BACKGROUND - The immune system has several mechanisms to fight against developing malignant cell clones in the host, one of them is the activated T-cell response. Both CD4+ helper and CD8+ cytotoxic T-cells bear CD69 and HLA-DR molecules as important surface activation markers. AIM - Our aim was to determine, how the ratio of activated T-cells change in the peripheral blood of non-Hodgkin-lymphoma patients during the periods of polychemotherapy. PATIENTS AND METHODS - We used the peripheral blood samples of 43 non-Hodgkin-lymphoma’s patients (20 females, 23 males, mean age 52.4 years). We determined the level of CD3+/HLADR+ and CD3+/CD69+ T-cell subsets before, during and after the periods of polychemotherapy, using the methods of immunofluorescence stain and flow cytometry. RESULTS - We found the ratio of CD3+/HLA-DR+ cells significantly higher in non-Hodgkin-lymphoma’s patients before treatment compared to healthy controls (10.63% vs. 2.97%, p<0.001). During the period of polychemotherapy, this ratio began to increase significantly (16.94% vs. 10.63%, p=0.006). The level of CD3+/CD69+ cells did not change significantly. After treatment, the ratio of activated T-cells decreased, however, we detected significantly higher rate of CD3+/HLA-DR+ lymphocytes in patients who relapsed within one year than in those who stayed in remission (9.55% vs. 20.62%, p<0.001). CONCLUSION - Investigation of CD3+/HLA-DR+ activated T-cells might be a promising method to determine the immune defence and this way the prognostics of lymphoma patients.]

Lege Artis Medicinae

SEPTEMBER 10, 2001

[Chlamydia pneumoniae in coronary arteries of young adults]

HORTOVÁNYI Eszter, ILLYÉS György, GLASZ Tibor, KULKA Janina, KÁDÁR Anna

[INTRODUCTION - An association of Chlamydia pneumoniae (C. pneumoniae) with coronary heart disease has been found with seroepidemiological methods. This organism was demonstrated in atheromatous plaques by electron microscopy, immunohistochemistry, and polymerase chain reaction. MATERIAL AND METHODS - To better understand the significance of the presence of C. pneumoniae in atheromatous plaques, we examined coronary artery segments from young adults (15-34 years) with and without atherosclerosis. 74 samples of left anterior descending artery were examined immunohistochemically for the presence of C. pneumoniae by the monoclonal antibody RR402. RESULTS - C. pneumoniae was identified in the atheroma in 11 of 17 cases (65%) and in preatheroma in 6 of 15 cases (40%), in fatty streak in 7 of 23 cases (30%) and in intimal thickening in 1 of 14 cases (7%). C. pneumoniae was not found in the intimal and medial layer of the normal-appearing coronary arteries. C. pneumoniae was detected in the adventitia in 51 cases (67%) of the coronary arteries: in the normal arteries and initial lesions in 27 of 42 cases (63%), and in the advanced lesions in 24 of 32 cases (75%). Correlation was observed between the C. pneumoniae positive cases and cigarette smoking. CONCLUSION - Our results suggest that C. pneumoniae may relate to the severity of atherosclerosis in the youth, thus may initiate atherosclerotic injury or facilitate its progression along with other risk factors.]