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Biomedical subjects

E Weigl

Publications and source records attributed to E Weigl.

At least 19 recordsLinked to original sources

CC chemokine receptor gene polymorphisms in Czech patients with pulmonary sarcoidosis.

Genes for the chemokine receptors CCR5 and CCR2 are characterized by polymorphisms resulting in a nonfunctional receptor expression. Ligands for CCR2 and CCR5 (chemokines monocyte chemotactic protein-1 [MCP-1] and RANTES) are implicated in the pathogenesis of sarcoidosis. We have, therefore, analyzed polymorphisms of CCR5 (32-bp deletion in CCR5 gene [Delta32]) and of CCR2 (replacement of valine by isoleucine in CCR2 gene [64I]) in 66 Czech patients with sarcoidosis in comparison with a representative sample of Czech normal population. The frequencies of CCR5Delta32 and CCR2-64I polymorphisms in patients with sarcoidosis were different from that in control subjects. CCR5Delta32 allelic frequency was significantly increased in patients. By contrast, the CCR2-64I allele was more frequent in control subjects; however, the difference did not attain significance. Interestingly, the CCR5Delta32 allele was associated with clinically more apparent disease: it was present in 39.1% of patients requiring corticosteroids but only in 16.7% patients who did not need therapeutic intervention (odds ratio [OR] = 2.9). When patients requiring corticosteroids were compared with control subjects, the differences in the CCR5Delta32 frequencies were enhanced (p < 0.01). In conclusion, the observed association of CCR5Delta32 and CCR2-64I with sarcoidosis implicates a role for these polymorphisms in disease susceptibility and protection.

Adolescent↗

Allergen standardization.

The article summarises current knowledge about the preparation and standardisation of treatment and diagnosis of allergies. It summarises the basic conceptions, units, methods and conditions for preparation, conservation and the storage of allergens. The article is especially orientated towards grass pollen.

Allergens↗

Heat shock proteins in immune reactions.

The review concerns heat shock proteins and their significance in immune reactions. It focuses on problems of physiological and pathological interactions in etiology and duration of autoimmune diseases and infection processes, especially fungal infections. New trends are described in exploitation of heat shock proteins for preparation of specific protective vaccines.

Animals↗

Development of the primer set for the detection of the hsp60 gene in Trichophyton mentagrophytes cDNA.

Three sequences of hsp60 from Saccharomyces cerevisiae, Schizosaccharomyces pombe and Histoplasma capsulatum were compared. Local multiple alignment of these sequences allowed the selection of two oligonucleotides suitable as primers for the polymerase chain reaction. This primer set was used for the amplification of a part of the hsp60 gene from cDNA of Trichophyton mentagrophytes and S. cerevisiae. Similar fragments detected in both PCR's imply the possible future use of the developed primer set for the detection of the hsp60 gene in other fungal species.

Base Sequence↗

Electrophoretic patterns of Trichophyton mentagrophytes mutants with changed growth rate at different cultivation temperatures.

Five mutants of Trichophyton mentagrophytes with changed optimum cultivation temperature and the wild strain were used in this study. The growth rates, the keratinolytic activities and the 1-D electrophoretic patterns of these mutants were examined repeatedly. The differences among the individual mutants and the wild strain can be useful for a better understanding of the participating individual proteins for thermotolerance of this fungus.

Child↗

Detection of antigens in mycelial and in arthroconidial phases of Trichophyton mentagrophytes.

Protein pattern changes were investigated in the filamentous fungus Trichophyton mentagrophytes during the morphological transition induced by increased temperature and higher CO2 partial pressure in cultivation atmosphere. The differences between the mycelial and the arthroconidial phase were characterized by SDS-PAGE and by immunodetection with mouse polyclonal antibodies. The components found by Western blotting in mycelia were 88, 86, 32, 29, 19.5, 18.5 kDa, in arthroconidia 108, 92, 88, 66, 56, 41, 39, 19.5 kDa. The results suggest the participation of some heat shock associated proteins of T. mentagrophytes in host immune response against mycotic infection.

Animals↗

Class I typing by PCR-SSP in Olomouc.

In this article, methodical experience and population data are given for application of PCR-SSP/ARMS method (Phototyping) to HLA class I typing in Olomouc. Phototyping is reliable method suitable for typing of small to medium number of samples. Method is fast enough for use in on-call service, resolution is better than the level of good serology, and price of method is comparable with serology. Our experience and tips are described below. Population data of healthy unrelated individuals for HLA-A, -B, -Cw are given in the tables.

Gene Frequency↗

The source and role of RANTES in interstitial lung disease.

The chemokine "regulated on activation, normal T-cell expressed and secreted" (RANTES) is a potent eosinophil and lymphocyte attractant with particular preference for CD45RO+ T-cells and eosinophils. These cells accumulate in the lungs of patients with sarcoidosis and fibrosing alveolitis. The purpose of this study was to determine whether RANTES mediates the inflammatory cell influx in these diffuse lung diseases. Cell types and number of bronchoalveolar cells expressing RANTES protein were investigated by immunocytochemistry using lavage cells obtained from 22 patients and 11 control subjects. Subsequently, RANTES messenger ribonucleic acid (mRNA) was semiquantitated using reverse transcription polymerase chain reaction (RT-PCR) methodology in unseparated lavage cell pellets in 26 patients and 13 control subjects. Cells expressing RANTES mRNA were identified by in situ hybridization. RANTES protein expression in lower respiratory tract (LRT) cells was identified in all study groups. The percentage of RANTES+ lavage cells in sarcoidosis was higher than in controls. RANTES was localized in the cytoplasm, mainly in alveolar macrophages (CD68+ cells) in sarcoidosis, and both in alveolar macrophages and eosinophils in fibrosing alveolitis. The same cell types which expressed RANTES protein expressed RANTES mRNA, as assessed by in situ hybridization. Sarcoidosis patients had higher levels of RANTES mRNA than the other groups. RANTES protein was higher in individuals with abnormal lymphocyte numbers: RANTES protein and mRNA expression was significantly correlated with lavage CD45RO+ lymphocyte numbers. These results indicate that RANTES may mediate T-lymphocyte influx in diffuse lung disease, particularly sarcoidosis. Moreover, they suggest that the cellular source of RANTES is the alveolar macrophage in sarcoidosis, and both macrophages and eosinophils in fibrosing alveolitis.

Bronchoalveolar Lavage Fluid↗

Differential chemosensitivity of leukemic cells in the myeloid and lymphoid phases of stem cell leukemia (a case report).

A five-year-old girl, initially diagnosed as having acute lymphoblastic leukemia (ALL; FAB-L1) relapsed with ALL 4 months after completion of chemotherapy (BFM 83). The initial ALL presentation and subsequent ALL relapse were analyzed using conventional morphology, cytochemistry, cytogenetics and immunophenotyping. The results were consistent with a diagnosis of B-lymphocyte precursor ALL. Bone marrow leukemic cells revealed a 46, XX karyotype at diagnosis and a 46, XX, del(7) (q22; qter) when the girl first relapsed. The case was managed with a BFM REZ-ALL 90 protocol. Upon completion of the first cycle of the protocol, severe myelosuppression developed. This was treated with GM-CSF. Three days later, however, GM-CSF was stopped because the WBC reached 1.1 x 10(9) per liter with 60% of blasts in peripheral blood. Laboratory characteristics were typical of AML. Cytogenetic analysis revealed 46, XX, del(7) (q22; qter) karyotype as before. The bcr-abl fusion gene was not detected. Myeloid blasts were placed in a culture and maintained at 37 degrees C and 7.5% CO2 for two weeks. During this period, formation of hemopoietic colonies was observed and subsequently analyzed using histology and electron microscopy. This showed that the colonies consisted of differentiating erythroid, megakaryocytic and myeloid cells. Further, the chemosensitivity of leukemic cells was examined in both "lymphoid" and "myeloid" relapse instances. While the "lymphoid" phenotype was characterized by good sensitivity to corticosteroids, a typical feature of the "myeloid" phenotype was a high resistance to corticosteroids with marginally increased sensitivity to ARA-C.

Antineoplastic Combined Chemotherapy Protocols↗

Decreased in vitro chemosensitivity of tumour cells in patients suffering from malignant diseases with poor prognosis.

The aim of the study was to assess the predictive value of MTT in vitro assay for evaluation of tumour cell resistance/sensitivity to cytotoxic drugs. We analyzed 105 samples of malignant cells of different origin. The study included patients with a diagnosis of acute and chronic lymphatic leukaemia, acute and chronic myeloid leukaemia, non-Hodgkin lymphoma, carcinoma of the lung, stomach and liver, rhabdomyosarcoma and breast carcinoma. The results demonstrate outstanding chemosensitivity in the majority of childhood acute lymphoblastic leukaemias, medium chemosensitivity of adult haematopoietic malignant diseases and chemoresistance of solid tumour cells. Our preliminary data suggest a good correlation between in vitro MTT assay and clinical curability of individual malignant diseases.

Adult↗

Bacterial immunomodulator Olimunostim inhibits degranulation of mastocytes in vitro.

A bacterial immunomodulator Olimunostim (OS) is one of the first Czech biologic response modifiers, which have been introduced into clinical practice. OS activates the mechanisms of non-specific immunity and is used for the most part in chronic infections. Since OS is indicated in patients suffering from infection complicated allergic diseases (asthma bronchiale, atopic eczema, etc.), (1) the concentration of histamine (Hi) and Hi-like compounds in OS, and (2) the possible role of OS in the process of histamine release from rat peritoneal mastocytes (PMC) were studied. The cells were preincubated with soluble fractions of OS. PMC degranulation was stimulated by the compound 48/80. The amount of Hi and Hi-like substances in the supernatant and in the pellet of PMC was determined by the fluorimetric method. Compounds of Hi nature were also evaluated in OS (lysate of S. aureus, K. pneumoniae, P. acnes) by original modification of high-performance liquid chromatography. The data provide the first evidence for a dose-dependent inhibitory effect of OS on the degranulation of rat PMC. Moreover, we found that 1 mg of OS itself contained 0.376 microgram of Hi and 0.142 microgram of 1-methylHi. Histamine was detected in P. acnes (0.672 microgram/mg), K. pneumoniae (0.136 microgram/mg), and S. aureus (0.175 microgram/mg), while methylHi was detected only in the case of K. pneumoniae (0.454 microgram/mg). The results of our in vitro study do not support the hypothesis of inducing type I allergic reaction by OS or facilitating OS in crossing the enteral barrier.

Adjuvants, Immunologic↗

The polybacterial lysate Olimunostim modulates lymphocyte function in vitro and restores depressed cellular immunity in vivo.

Immunobiological activity of the polybacterial lysate Olimunostim (P. acnes, K. pneumoniae, S. aureus) was examined by investigating its effects on murine lymphocytes. When added to in vitro lymphocyte cultures, Olimunostim induced interleukin-2 (IL-2) biological activity (in a 2-d culture) and subsequently potentiated lymphocyte proliferation (on day 3); the latter effect was dependent on the presence of adherent cells. In vivo, significant enhancement of lymphocyte reactivity to T-mitogens and increase of CD4+ helper-inducer T lymphocytes were observed 3 d after a subcutaneous application of Olimunostim to mice with cellular immune deficiency. These results confirm the modulatory properties of Olimunostim towards lymphocytes both in vitro and in vivo, which may form a basis for its clinical application.

Adjuvants, Immunologic↗

Some biochemical characteristics of the early phase of immunomodulation.

The study estimates some biochemical changes of chosen immunological and biochemical parameters after intraperitoneal application of a) immunomodulators of microbial origin--Propionibacterium acnes and Geotrichum candidum, b) chemical substances--indomethacin and phenobarbital. The estimation was concentrated above all to the changes of chemiluminiscence, phagocytic activities, the amount of cAMP in peritoneal macrophages, the amount of liver cytochrome P-450 and cAMP in the liver, spleen and thymus. The experiments also included histological examination of the spleen, thymus, lungs and diaphragm. The effect of Propionibacterium acnes was evident as soon as 24 hrs after application. In the frame of studied parameters, there was manifested the nonspecific activation of the immune system by the mechanisms independent to oxygen. The early changes were accompanied by the increase of cAMP in macrophages. In contrary, the intraperitoneal application of Geotrichum candidum activated the release of oxygen radicals from peritoneal macrophages. The amount of the cytochrome P-450 correlated to the intensity of immunomodulation. On the other hand, the induction of cytochrome P-450 by phenobarbital decreased the value of several immunity indices.

Adjuvants, Immunologic↗

Effect of quaternary benzo[c]phenanthridine alkaloids sanguinarine, chelerythrine and fagaronine on some mammalian cells.

The effects of benzo[c]phenanthridine alkaloids sanguinarine (SA), chelerythrine (CHE), fagaronine (FA) and their dihydroderivates were tested on human leukocytes and lymphocytes, rat peritoneal mastocytes and primary cultured hepatocytes. The cytotoxicity of SA and CHE on hepatocytes is dose (35-100 microM) and time (1-3 h) dependent. Both alkaloids decrease chemiluminiscence of leukocytes and inhibit a creation of active E-rosets. The degranulation of mastocytes is inhibited only by CHE. Dihydroderivates of SA and CHE did not display any effect on studied cells, dihydrofagaronine exhibits a hepatotoxicity after 3 h.

Alkaloids↗

Biochemical aspects of immunomodulation by Propionibacterium acnes.

The present paper deals with the effect of indomethacin and/or Propionibacterium acnes (Pa) on the cytochrome P-450 content in liver microsomal fraction, free fatty acids and lipase concentration in serum with respect to the phagocytic activities of monocytomacrophage system, changes in weight of the spleen and liver, survival after LD100 of Klebsiella pneumoniae, and histology of the spleen and liver. The results obtained indicate that INDO acts as an inhibitor of cytochrome P-450 and at the same time stimulates functions of the monocytomacrophage system in all the parameters studied. Pa, a classical immunomodulator, inhibits cytochrome P-450. After the initial suppression phase (3rd day after administration), it stimulates significantly the activity of monocytomacrophage system and increases the amount of FFA in the serum. The combination of both preparations also inhibits the cytochrome P-450 concentration in the liver and stimulates functions of the monocytomacrophage system in all the studied parameters. However, no temporary suppression of phagocytic activities was observed on the 3rd day of the experiment, in contrast to the animals administered Pa alone. Serum FFA concentration increased significantly. The application of both preparations accelerated markedly the onset of proliferation and differentiation processes in lymphatic follicles of the spleen.

Adjuvants, Immunologic↗

Genetics of dermatophytes.

By the end of 60s a team of scientists has started at Medical Faculty of Olomouc the research of micromycetes pathogenic for both the humans and animals. In this study, the appropriate results are summarized as concerned with the genetics of dermatophytes. Among these results, those significant in deeper assessing the biology of dermatophytes and etiopathogenesis of dermatophytoses have been selected. In our opinion, they may be of interest for the successors in the direction mentioned. Here are also formulated certain open problems and the applicative outputs are traced, for example, those concerning with vaccines. The approaches used, even unusual in the medical mycology from a traditional scope, are believed to prove the convenience of genetic methods when researching mycopathogens. We regret to miss at the edition of this publication the late founder of the team, RNDr. Nora Hejtmánková, CSc. which had the greatest contribution to the Chapters on the karyology and variability of dermatophytes as well as to the hybridization analysis of Trichophyton mentagrophytes complex.

Arthrodermataceae↗

Lymphocyte proliferation and T-lymphocyte subsets during experimental immunomodulation of Balb/C mice by Olimunostim.

To objectivize possible immunomodulatory effects of polybacterial lysate Olimunostim (P. acnes, K. pneumoniae, S. aureus), splenic lymphocyte proliferation and T-lymphocyte subsets were followed-up in Balb/c mice administered perorally the lysate or saline (controls). The enhanced spontaneous lymphocyte proliferation observed at the beginning of Olimunostim application preceded a gradual increase of lymphocyte reactivity to T-mitogens reaching the maximum five days after the administration of the last dose and returning back to the control levels ten days afterwards. This stimulation of lymphocyte proliferation was accompanied by Olimunostim induced increase of CD4+ splenic lymphocytes being most pronounced five days after the end of immunomodulation and later returning to the initial values. The last experiment revealed an enhanced response of the in vivo primed lymphocytes after the re-exposure to Olimunostim in vitro. It is concluded that mostly nonspecific activation mechanisms, plausibly also parallelly induced specific immunity, are involved in Olimunostim modulatory effects on the cellular immune response.

Adjuvants, Immunologic↗