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V Kolek

Publications and source records attributed to V Kolek.

At least 19 recordsLinked to original sources
PubMed2002

CC and C chemokine expression in pulmonary sarcoidosis.

The chemokines RANTES (regulated on activation, T-cell expressed and secreted; CC chemokine ligand (CCL)-5) and monocyte inflammatory protein (MIP)-1alpha (CCL-3) have been implicated in the development of alveolitis in pulmonary sarcoidosis. The novel C chemokine single cysteine motif (SCM)-1alpha (XCL-1) and the CC chemokine monocyte chemoattractant protein (MCP)-1 (CCL-2) are also mononuclear-cell attractants and represent alternative candidate mediators of alveolitis. Therefore, the expression of MCP-1 and SCM-1alpha was investigated together with the expression of RANTES and MIP-1alpha in bronchoalveolar lavage fluid (BALF) from control subjects and patients with sarcoidosis. The relationship between chemokine expression and sarcoidosis clinical course was also explored. Messenger ribonucleic acid (mRNA) expression for all four chemokines was determined by semiquantitative reverse transcriptase-polymerase chain reaction of RNA extracted from unseparated bronchoalveolar cells (17 patients, 12 controls). RANTES, MIP-1alpha and MCP-1 proteins were measured by enzyme-linked immunosorbent assay of unconcentrated BALF (60 patients, 17 controls). MCP-1, and namely RANTES and SCM-1alpha mRNA expression was upregulated in sarcoidosis, particularly in patients with more advanced disease. RANTES, and namely MCP-1 concentrations were elevated in BALF samples obtained from patients; MCP-1 levels were most increased in patients with chest radiographic stage 2 disease and also in patients with persistent and recurrent disease. In conclusion, chemokines monocyte chemotactive protein-1 and single cysteine motif-1alpha are, in addition to RANTES, associated with the development of alveolitis in sarcoidosis and their expression parallels the disease course.

Adult↗
PubMed2001

Ace gene I/D polymorphism and sarcoidosis pulmonary disease severity.

Previous studies of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in sarcoidosis have revealed both ethnic heterogeneity of I/D frequencies and controversy surrounding the association between the polymorphism and severity of disease. The objective of this study was, therefore, to clarify the role of the ACE I/D polymorphism in (1) disease susceptibility, (2) pulmonary disease severity (with particular reference to pulmonary fibrosis), and (3) pulmonary disease progression, in two distinct European sarcoidosis populations. Standard chest radiographic staging was performed on 118 UK and 56 Czech white patients with sarcoidosis at 2 yr from presentation. Pulmonary function data were analyzed, and patients were then categorized according to disease severity. A PCR-SSP assay was used to determine the ACE I/D genotype of each patient studied. The I/D allele frequencies from these patients were compared with frequencies from ethnically matched UK (n = 386) and Czech (n = 179) control subjects using a chi-square contingency table. No significant differences were seen in the distribution of the ACE I/D genotypes, allele frequencies or phenotype frequencies. Furthermore, no association was found between the ACE I/D polymorphism and pulmonary disease severity, fibrosis, and progression. We conclude that the ACE I/D polymorphism has no role in sarcoidosis susceptibility in European whites and that it is not a regulatory variant in this disease.

Adult↗
PubMed2001

[Fire-eater's pneumonia--a difficult differential diagnosis].

Acute aspiration of petroleum or other hydrocarbon products can cause a distinct type of chemical pneumonitis known as fire-eater's pneumonia. Initial findings on chest X-rays are ambiguous and not uniform in nature. Among the most common belong mottled or patchy, local or diffuse perihilar and basal uni- or bilateral infiltrates, areas of atelectasis, tumor-like lesions and rarely pleural effusions. CT finding often shows formation of smaller or larger pneumatoceles. Those cavities tend to regress spontaneously over weeks or months. Clinical diagnosis is sometimes very difficult, especially in cases, when past history of "fire-eating" is not known to the physician. The authors present clinical manifestation, sequential X-ray and CT findings in one patient with fire-eater's pneumonia. To diagnose the disease, not only paraclinical exploration is needed, but also the patient's past history plays an important role. Without it this puzzling clinical unit can remain undiagnosed.

Adult↗
PubMed2001

Human leukocyte antigen-DRB1 position 11 residues are a common protective marker for sarcoidosis.

Genetic factors, in particular human leukocyte antigens (HLAs) are important determinants of susceptibility to sarcoidosis, a chronic granulomatous disease of undetermined etiology. To clarify the role of HLA in sarcoidosis we determined HLA-DR and -DQ alleles in case-control samples from three European populations (United Kingdom, Czech, and Polish) and compared these results with those published for three additional populations (Italian, Japanese, and Scandinavian) to determine whether the HLA-DR and/or -DQ alleles act as ethnic-dependent, or ethnic-independent modifiers of disease risk. Although variations were apparent in the alleles associated with susceptibility, reductions in the frequency of alleles associated with protection were remarkably consistent in the six populations. Previously detected associations between single-nucleotide polymorphisms at the TAP2 locus and sarcoidosis were shown to be due to linkage disequilibrium with the HLA-DR locus. The protective HLA-DR alleles, which encode the DR1 and DR4 antigens, were found to share characteristic small hydrophobic residues at position 11, which were replaced by small hydrophilic residues in the remaining, nonprotective, HLA-DR alleles. This residue position is within a pocket of the HLA-DR complex antigen binding groove (designated P6), where it is the only variable amino acid and therefore determines the peptide binding preferences of this pocket. A highly significant reduction in the frequency of individuals carrying HLA-DR alleles with a hydrophobic residue at position 11 was observed in the sarcoidosis cases in the three populations we examined. This suggests this HLA-DR residue is an important protective marker in sarcoidosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Serum Clara cell protein (CC16), a marker of the integrity of the air-blood barrier in sarcoidosis.

To test the hypothesis that sarcoidosis is associated with an intravascular leakage of lung epithelium secretory proteins, the occurrence and determinants in serum of sarcoid patients of CC16, a small size and readily diffusible lung-specific protein of 16 kDa secreted by bronchiolar Clara cells, was investigated. CC16 was measured by a sensitive latex immunoassay in the serum of 117 patients with established sarcoidosis and of 117 healthy subjects matched for age, sex and smoking status. Stepwise regression analysis was used to identify extrapulmonary variables of CC16 changes in serum. These changes were then compared with biochemical and cellular parameters in bronchoalveolar lavage fluid (BALF) as well as with the number of CC16 immunostaining cells on bronchial or pulmonary biopsy samples. CC16 concentration in serum of sarcoid patients was significantly increased, compared to their matched controls (25.9 +/- 16.2 versus 13.9 +/- 5.2 microg x L(-1)). In nonsmoking patients without significant renal impairment, CC16 in serum increased with the severity of the chest radiograph and computed tomography changes, and was on average 50-100% higher when parenchymal involvement was present. Sarcoid patients had, however, normal levels of CC16 in BALF and an unchanged number of CC16-immunopositive cells in lung biopsy samples, suggesting that an increased secretion of CC16 in the sarcoid lung is very unlikely, and that the elevation of CC16 in sarcoidosis results from an increased intravascular leakage of the protein across the air-blood barrier. The present study suggests that CC16 in serum might provide a useful tool to noninvasively evaluate the damage and increased permeability to proteins of the air-blood barrier associated with sarcoidosis.

Adult↗
PubMed2000

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↗
PubMed2000

[Significance and possibilities of cytostatic treatment of malignant tumors: testing the effects of cytostatics].

The authors present an account on the initiation of a study concerned with the administration of cytostatics according to the sensitivity of the tumour cells. To assess the sensitivity the MTT test was used. The method is described in the paper. Four groups of tumours were examined by the MTT test: breast cancer, carcinoma of the colon and rectum, of the lungs and oesophagus + stomach. Six cytostatics were tested: 5-fluorouracil, cisplatinum, daunorubucin, paclitaxel, vincristine, and vepeside. Evaluation of the sensitivity of different tumours was based on the median of TCS50. The results of the MTT test were not used so far in the therapeutic protocol in all patients where the examination was made, as in solid tumours, contrary to haemo-blastomas, usually common empirically tested protocols are used. The authors reflect whether individually administered cytostatics according to the MTT test can improve the prognosis of patients with malignant diseases. They assume that long-term follow-up of the patients may provide favourable results in particular because more and more effective cytostatics are becoming available.

Antineoplastic Agents↗
PubMed2000

[Assessment of metastatic potential of pulmonary carcinoma].

The authors evaluated in a group of 25 patients after radical lung resection on account of a non-small cell carcinoma the correlation between tumour grading, invasion into lymphatic and blood vessels, proliferation markers (Ki-67, PCNA), ploidy, cell polymorphism and mitotic cell activity of the lung tumour and the lymphogenic or haematogenic metastatizing proved before or during surgery. From the investigation patients after induction chemotherapy were eliminated. It was of interest that the great majority of investigated parameters was positive or elevated in patients with lymphogenic or haematogenic metastases. Conversely in patients where the majority of these parameters was negative on the day of the operation, no metastases were detected. In the group of patients where the investigated indicators were positive and no metastasis was found, similarly as in both previous sub-groups, the author will continue to follow-up the following: recurrence, median survival and five-year survival. From the assembled parameters a table was prepared stratifying the risk of metastases.

Biomarkers, Tumor↗
PubMed1997

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↗
PubMed1996

[Neurosarcoidosis. Role of new examination methods for early diagnosis and therapy].

BACKGROUND: Affection of the nervous system is one of the most serious forms of sarcoidosis. The objective of the present work was to evaluate the prevalence and manifestations of this disease, contemporary opportunities of its diagnosis and the importance of early adequate therapy. METHODS AND RESULTS: Neurosarcoidosis was diagnosed in seven patients (4 men and 3 women) from a total number of 211 patients with sarcoidosis in 1977 to 1993. The mean age of the patients with neurosarcoidosis was 47 years. In six patients affection of the nervous system was the first clinical manifestation of the disease. In four patients it was paresis of the facial nerve, in two instances diabetes insipidus, in two instances affection of the spinal cord with subsequent spastic triparesis or paraparesis of the lower extremities, in one instance the disease was manifested by neuralgia of the trigeminal nerve. The serious character of the disease is apparent from the fact that only in two instances complete regression of symptoms occurred. In three patients regression was partial, in one instance the affection persisted without changes and in one instance it progressed to metabolic breakdown with a fatal outcome. In the differential diagnosis examination of the nervous system by computed tomography, magnetic resonance and possibly perimyelography proved to be helpful. In all instances there was a typical finding in cerebrospinal fluid. Lymphomonocytic pleocytosis was present, a raised protein content, elevated gammaglobulin levels. The diagnosis was assisted by radiograms of the chest and biopsy. The latter was made from intrathoracic or subcutaneous nodes, in one instance from muscle. As auxiliary methods the following were used: tuberculin test, bronchoalveolar lavage, pulmonary gallium scintigraphy, serum level of angiotensin converting enzyme and immunological examination. CONCLUSIONS: The authors emphasize the necessity of early diagnosis and intensive initial treatment with corticoids or antimalaria drugs, which may prevent the development of irreversible changes. Magnetic resonance appears to be the most promising examination method in neurosarcoidosis.

Adult↗
PubMed1996

[Treatment of inoperable non-small cell bronchogenic carcinoma with a combination of cisplatin and vinorelbine--preliminary evaluation].

The optimal therapeutic approach to patients with inoperable non-small-cell carcinoma is still a matter of discussion. The reason is that chemotherapy improves the quality of life only in some patients. It prolongs their life only by several weeks. In recent years in this indication a new cytostatic is tested--vinorelbine which when used in monotherapy achieves a therapeutic response in 16--30%. In clinical trials of phase 2 a combination of vinorelbine and cisplatinum was most effective and therefore it was selected for the third phase of clinical trials. In the Czech Republic a clinical investigation was made with the objective to verify published data on the success of treatment, evaluate undesirable effects and consider whether it is suitable for routine use. Cisplatinum (Platidiam Lachema) was administered--80 mg/m2 on the first day, vinorelbine (Navelbine Pierre Fabre)--30 mg/m2 on the first and eighth day. The cycle was repeated on the 22nd day. All patients were treated for 12 weeks. Then followed the first evaluation and treatment was continued only in patients with regression or stabilization of the disease. In the group of 126 patients in 44 (35%) partial and in 3 (2.3%) complete therapeutic responses were obtained. In 35 (27%) the disease was evaluated during treatment as stabilized, in 38 (30%) of the patients the disease progressed despite treatment. The tolerance of treatment was, when effective antiemetic treatment was used (ondansetrone or granisetrone), relatively satisfactory.

Antineoplastic Agents↗
PubMed1995

"The sarcoidosis map": a joint survey of clinical and immunogenetic findings in two European countries.

We pooled immunogenetic data obtained in independent studies in two European populations (Italian and Czech) of patients affected by sarcoidosis. Correspondence analysis was used to investigate the associations between clinical and immunogenetic data. Two hundred and thirty-three patients were enrolled in the study, of which 126 were from the Czech Republic and 107 from Italy. Using a common protocol, we examined each patient for sex, age of disease onset, roentgenologic stage, extrapulmonary spread, and clinical course. One thousand and ten healthy individuals, HLA typed for class I and II serologic polymorphisms, served as controls. Findings that were essentially in agreement in both populations were: (1) a positive association of sarcoidosis with HLA-A1, B8, and DR3 markers, and a negative association with HLA-B12 and DR4; (2) a prevalence of HLA-DR3 and DR4 among females and of DR5 among males; (3) a relationship of B13 and B35 with early onset and of A30, B8, DR3, and DR4 with late onset of disease; (4) an association of B27 with sarcoidosis restricted to the lungs; (5) a relationship of A1, B8, B27, and DR3 to roentgenologic stage I and of B12 and DR4 to stage III; and (6) an association of HLA-DR3 with a good outcome. Population-restricted findings essentially concerned the alleles HLA-B13 and B22, the former being associated with the disease, male sex, early onset, extrapulmonary localization and relapse only in Czechs, and the latter to disease spread only in Italians. Our results seem to support the concept that immunogenetic background may at least partly account for the clinical heterogeneity of sarcoidosis.

Adult↗
PubMed1995

Vinorelbine and cisplatin in the treatment of advanced non-small cell lung cancer: results of a multicenter Czech study.

There is continuous discussion about the optimal treatment for patients with inoperable non small cell lung cancer. This is because chemotherapy can only improve the quality of life in a fraction of treated patients while prolonging survival by a couple of weeks at best. The new cytostatic drug "vinorelbine" has been tested in this indication during the last years. The drug has reached the response rate of 16 to 30% when used as monotherapy. The phase II studies proved the combination of vinorelbine with cisplatin to be the most efficient one and this combination was picked up for phase III clinical trials. The clinical trial with the aims to verify published data on treatment efficacy, to assess adverse effects of treatment and to evaluate appropriateness for routine application has been made in the Czech Republic. The treatment schedule was as follows: cisplatin (Platidiam Lachema) in a dose of 80 mg/m2 on day 1, vinorelbine (Navelbine Pierre Fabre) in a dose of 30 mg/m2 on days 1 and 8. The whole cycle was repeated on day 22. The treatment was applied for 12 weeks. After that the efficacy of treatment was evaluated and only the patients with regression or stabilization of the disease continued the treatment. 44 (35%) partial remissions and 3 (2.3%) complete remissions were achieved in a group of 126 evaluable patients. The effect of treatment was evaluated as stable disease in 35 (27%) patients while the progression of disease occurred in 38 (30%) patients. The tolerance of treatment using effective antiemetic support (ondansetron or granisetron) was fairly good.

Adult↗